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N Jørgensen

Publications and source records attributed to N Jørgensen.

9 recordsLinked to original sources

Trends in incidence of testicular cancer in boys and adolescent men.

Several epidemiological studies have described increasing trends over time in the incidence of testicular cancer in adult men. Less attention has been given to the trends in young boys, adolescents and old men. This paper describes the incidence of testicular cancer in young boys (0-4 years) and adolescents (15-19 years) in Denmark, Norway and Sweden, and compares these trends with the corresponding data on adults. Although only small numbers were available, the data suggest that the incidence of testicular cancer in young boys has been constant, at a level around 0.5 per 100,000. This observation lends support to the idea that testicular cancer in young boys is aetiologically distinct from testicular cancer in adults. In all three populations we found a particularly high average annual increase in the incidence of testicular cancer in adolescents (around 6% per year). It is proposed that this increase is mainly caused by a secular trend towards earlier age at puberty.

Adolescent

DNA content and expression of tumour markers in germ cells adjacent to germ cell tumours in childhood: probably a different origin for infantile and adolescent germ cell tumours.

The origin of testicular germ cell tumours occurring during childhood is poorly understood. In adults, the classical seminomas and non-seminomas originate from carcinoma in situ of the testis, which can usually also be detected in seminiferous tubules adjacent to the tumours. In order to contribute with information regarding a possible association between carcinoma in situ and the childhood group of germ cell tumours, we investigated seminiferous tubules adjacent to 13 infantile yolk sac tumours, five infantile teratomas, and six adolescent germ cell tumours of various types, using morphological evaluation, immunohistochemical staining with markers for carcinoma in situ cells, and densitometric DNA measurement of the germ cells. We detected clear differences between the germ cell populations adjacent to adolescent and infantile germ cell tumours. The former were associated with both normal germ cells and carcinoma in situ cells, like germ cell tumours occurring in adult men. Although we were in doubt in two cases, the infantile cell germ cell tumours were in general not associated with carcinoma in situ cells. The aetiology of infantile yolk sac tumours and teratomas may therefore be fundamentally different from that of adolescent and adult germ cell tumours. The origin of yolk sac tumours and teratomas remains to be elucidated.

Adolescent

Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells.

BACKGROUND: It has been hypothesized that carcinoma in situ of the testis (CIS), which is the precursor of invasive testicular germ cell tumours, may arise from fetal germ cells during fetal development rather than later in life. In order to corroborate this hypothesis, we undertook the present study. EXPERIMENTAL DESIGN: Normal human germ cells from 10 first-trimester fetuses and 76 second- and third-trimester testes were investigated for the immunohistochemical expression of the markers of testicular carcinoma in situ. The panel of markers included in the study consisted of placental-like alkaline phosphatase, the protooncogene c-kit protein product, and the antigens for the monoclonal antibodies TRA-1-60 and M2A. The relative numbers of fetal germ cells that demonstrated positive reaction with the markers were calculated. RESULTS: The vast majority of the germ cells (75-100%) in the first-trimester gonads were positive for placental-like alkaline phosphatase, TRA-1-60, and M2A. The c-kit protein was detected in three out of the ten first-trimester gonads. The relative number of germ cells positive for all the markers studied declined rapidly during the first part of the second trimester, and the decrease continued with the fetal age. CONCLUSIONS: The expression of adult carcinoma in situ markers in normal fetal germ cells is consistent with the hypothesis that CIS cells may arise from fetal germ cells, although re-expression of the antigens in postnatally arising CIS cells could provide an alternative explanation. However, we speculate that a transformation of normal fetal germ cells into CIS cells may take place before the end of the 9th week of fetal development. Furthermore, the expression of c-kit in early human fetal germ cells indicates that the c-kit and its ligand play a role in the early human testicular development.

Alkaline Phosphatase

Testicular germ cell tumours of childhood in Denmark, 1943-1989: incidence and evaluation of histology using immunohistochemical techniques.

In the Danish Cancer Registry, 72 testicular tumours in boys younger than 15 years of age were recorded during the period 1943-1989 and material from 34 of these was retrieved from Danish departments of pathology. The histological types were evaluated and the role of immunohistochemical staining was analysed. The survival of the patients was correlated with the histological diagnoses, and changes in the incidence of testicular cancers in childhood were analysed. Twenty-nine of the 34 patients had germ cell tumours, which fell into two groups (infantile and pubertal) with distinct differences. The tumours of infancy usually presented before the age of 3 years and were either pure yolk sac tumours or teratomas. The tumours of puberty showed no morphological or immunohistochemical differences from adult germ cell tumours. In the infantile group, immunohistochemical staining confirmed the morphological evaluation but was not necessary for diagnosis. Patients in the infantile group seemed to have a better prognosis than adult patients, only one patient dying from his disease, whereas the pubertal patients seemed to have a prognosis similar to that of adult patients. The incidence of infantile testicular cancer in Denmark appears to have increased at almost the same rate as that observed in adult men, but due to the small numbers in infancy, this cannot be statistically substantiated. We conclude that the testicular germ cell tumours of infancy and puberty may arise from different precursor cells, but both groups seem to arise prenatally.

Adolescent

DNA distributions in maldescended testes: hyperdiploid aneuploidy without evidence of germ cell neoplasia.

Fine-needle aspiration biopsies and surgical biopsies were obtained from maldescended testes of 149 consecutive men. The aspirates were subjected to quantitative DNA flow cytometry and the surgical biopsy to histological evaluation. From more than 80% of the gonads, sufficient material was obtained for both examinations. A significant hyperdiploid cell population with a mean DNA index of 1.23 (range 1.17-1.31) was found in six gonads. Hyperdiploid aneuploidy was found in gonads without, as well as with, complete spermatogenesis. In none of the six cases did the surgical biopsy show evidence of early testicular neoplasia by morphology or by immunohistochemical methods with antibodies against carcinoma in situ. This indicates that aneuploidies in maldescended testes do not necessarily indicate malignancy. It may be speculated that hyperdiploid aneuploidy is related to the development of preneoplastic lesions.

Adult

Clinical and biological significance of carcinoma in situ of the testis.

Carcinoma in situ (CIS) of the testis is a preinvasive lesion that with time progresses into invasive germ cell tumour. CIS precedes all types of germ cell tumours except spermatocytic seminoma. An increased risk of harbouring CIS has been reported in men with a history of cryptorchidism, in contralateral testes of men previously treated for unilateral germ cell tumour, in intersex patients, in men with assumed extragonadal germ cell tumour and possibly in infertile men. CIS develops into invasive germ cell cancer in 50% of untreated patients within five years of diagnosis, and it is believed that with time CIS will progress into germ cell cancer in almost all patients. A testicular biopsy is necessary to diagnose CIS. Cells with the characteristics of CIS cells have been detected in seminal fluid, and it may be possible to develop methods for diagnosing the condition by analysis of the semen. We recommend orchidectomy as the treatment of choice in cases of unilateral CIS, if the other testis has a potential for fertility. In other cases, such as patients with testicular tumour and CIS of the contralateral testis, we recommend localized irradiation of the testis with CIS. Leydig cell function seems to be slightly impaired, but sufficient for sexual function, after irradiation. CIS cells show morphological and immunohistochemical similarities with primordial germ cells (gonocytes), whereas they share only few features with spermatogonia. Therefore, we suggest that CIS cells are malignant cells derived from gonocytes during embryonic development.

Carcinoma in Situ

Valproate and palmitate binding to human serum albumin: an hypothesis on obesity.

Binding equilibria of valproate (2-n-propyl-pentanoic acid anion) with defatted human serum albumin were studied by equilibrium dialysis in a 66 mM sodium phosphate buffer, pH 7.4, 37 degrees. Three hundred and fifty-six observed points for bound versus free valproate concentration were obtained and analyzed in terms of stepwise binding. It was found that the best fit resulted from a model in which 67% of the albumin was capable of binding valproate, whereas 33% did not bind. Thirty acceptable variants of the curve fitting were generated in order to assess the variation of the binding constants. The binding albumin component combines with three molecules of valproate with high affinity and with at least seven additional molecules that are loosely bound. Saturation of the protein cannot be reached. At very high concentrations of free valproate (above 10 mM) irreversible changes in the albumin take place, resulting in poor reproducibility in the amount of bound valproate. In the presence of palmitate, 0.5, 1, and 1.5 mol/mol of albumin, binding of valproate is decreased by a competitive mechanism. It is hypothesized that obesity, developing as a complication of valproate treatment of epilepsy, results from increased availability of long-chain fatty acids due to competitive valproate binding.

Humans

Early diagnosis of acute myocardial infarction with a rapid latex agglutination test for semi-quantitative estimation of serum myoglobin.

A rapid latex agglutination test for the detection of elevated levels of myoglobin in serum was evaluated in a prospective study of 236 patients consecutively admitted to a Coronary Care Unit on suspicion of acute myocardial infarction (AMI). The final diagnosis was made according to the WHO criteria. The prevalence of AMI was 0.45 with a male to female ratio of 2:1. In all patients at least two blood samples were collected with 4 hours interval 4-12 hours after the onset of symptoms. All sera were analysed for myoglobin by a latex agglutination test and by a radioimmunoassay (RIA). The latex test was performed twice, first as an emergency test by the technical assistant on duty and later by another well-trained technical assistant as her daily routine work. If the latex test was carried out each day by the same well-trained technical assistant, the test results agreed well with the RIA test results, and the false-negative fraction for patients with AMI constituted 0.06 and the false-positive fraction for patients without AMI 0.46. However, when the latex test was performed by the occasional technical assistant on duty, a relatively high degree of discrepancy was observed between the latex test results and the RIA test results, thus giving a false-negative fraction of 0.11 and a false-positive one of 0.36. In conclusion, performed under optimal laboratory conditions, the latex test can be used as a reliable method to estimate elevated levels of serum myoglobin. However, used as a bedside emergency examination, the test results correlated rather poorly to the RIA test results, and consequently the latex myoglobin test seems to be of minor clinical importance in the early evaluation of patients with suspected AMI.

Female