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A Giwercman

Publications and source records attributed to A Giwercman.

At least 91 records · Page 5Linked to original sources
PubMed1996

Identifying environmental risk to male reproductive function by occupational sperm studies: logistics and design options.

Malfunction of the male reproductive system might be a sensitive marker of environmental hazards, the effects of which may extend beyond reproductive function. The testis is more vulnerable to heat and ionising radiation than any other organ of the body and several xenobiotics are known to disrupt spermatogenesis after low level exposure. Studies of environmental impact on human health are often most informative and accurate when carried out in the workplace where exposures can be high and easy to document. Semen analysis provides readily obtainable information on testicular function. The main advantages in comparison with functional measures such as fertility rates and time taken to conceive are the possibilities to examine men independently of marriage and pregnancy, to find changes of fecundity with different exposures within the same person and to detect adverse effects when no alteration of fertility is yet taking place. In the implementation of an occupational sperm study considerable attention must be paid to logistic issues. A mobile laboratory unit for initial semen preparation and processing may in some situations increase worker compliance and the quality of sperm cell motility. The cross sectional design which has been used in almost all male reproductive studies so far has several severe limitations including selection bias because of differential participation, difficulties in defining a suitable reference group, and lack of information about the time dimension of the cause-effect relation. The longitudinal design deals adequately with most of these constraints. Semen samples are collected before, during, and possibly after exposure to the risk factor of interest and causal inferences are based upon change of semen variables within a man over time rather than upon differences between men. The logistics of the longitudinal study may benefit from pre-employment health examinations to enrol newly hired workers and require fewer participants to obtain comparable statistical power. In conclusion, andrological methods and epidemiological designs are available for the implementation of valid studies concerned with environmental impact on human testicular function. Occupational sperm studies should probably not be the first choice when the objective is initial screening of environmental impact on fertility but should be implemented when their is a need to corroborate or refuse earlier evidence that specific exposures have impact on testicular function.

Biomarkers↗
PubMed1996

Male reproductive health and environmental xenoestrogens.

Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.

Animals↗
PubMed1996

Should the other testis be biopsied?

Testicular tumors are bilateral in approximately 5% of the cases, although the incidence of bilaterality is affected by the treatment of the primary tumor. A biopsy of the contralateral testis of testicular tumor patients will show carcinoma in situ (CIS) in 5% to 6% of cases. Virtually all untreated cases of CIS will progress into invasive testicular germ cell tumors. In some countries, most testicular tumor patients have a contralateral biopsy at the time of the primary orchiectomy; but in many countries, urologists are not always aware of the advantages of simultaneous contralateral biopsy. The policy in the United States does not encourage surgeons to perform a contralateral biopsy at the initial orchidectomy or to offer a biopsy to patients after referral to a specialist center. The diagnosis of CIS is not of mere academic interest, but makes it possible to offer the patient optimal treatment.

Adult↗
PubMed1995

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↗
PubMed1995

Incidence of testicular mononuclear cell infiltrates in normal human males and in patients with germ cell neoplasia.

The incidence of mononuclear cell (MNC) infiltrates was studied in the testes of the following: 45 patients with carcinoma in situ (CIS) as the only lesion in the testis, CIS accompanied by an early invasion of CIS or CIS accompanied by invasive germ cell tumour (GCT) of the testis; 100 men and 146 boys who had died suddenly and unexpectedly, and 100 infertility patients. The results suggest that (1) the incidence of MNC infiltration increases with increasing severity of testicular malignant changes, (2) increased MNC infiltration is also evident in the contralateral testis where no malignant cells can be observed, (3) the incidence of MNC infiltration in men who died suddenly is not different from that in men who have had their testes biopsied because of infertility, and (4) the incidence of MNC infiltration is high in testes of boys younger than 1 year of age.

Adolescent↗
PubMed1995

Declining semen quality and increasing incidence of testicular cancer: is there a common cause?

Male reproduction has been given little attention in science and in medical practice. However, a recent metaanalysis on semen quality, which clearly pointed to a decrease over the past 50 years, has been repeatedly quoted. Three recent reports have found that semen quality has declined among candidate semen donors during the past 20 years. The evidence of decline in the quality of semen is not the only indicator that the human testis is at risk. During the past 50 years, cancer of the testis has also become more common. This is a disorder of young men, and it is associated with a high rate of other abnormalities of the testis including undescended testis and poor semen quality. Furthermore, the incidence of both hypospadias and undescended testis has been reported to be rising in the general population. We believe that the evidence of declining semen quality should be seen in the light of these trends in other reproductive disorders of men. However, the etiology is unknown. A recent hypothesis that links the trends in the health of the male reproductive system to xenoestrogens in the environment is discussed.

Adult↗
PubMed1995

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↗
PubMed1994

Current concepts of radiation treatment of carcinoma in situ of the testis.

During a recent international workshop on carcinoma in situ and cancer of the testis held in November 1992, there was consensus about the management of the contralateral testis in patients with unilateral testicular cancer [20]. Such men should be offered a biopsy of the contralateral testis. This consensus was based on (1) the high prevalence of carcinoma in situ (CIS) in the contralateral testis found not only in Danish men but also in studies from other countries and (2) the possibility of eradicating the CIS and thereby preventing the development of invasive cancer by means of localized irradiation with preservation of testosterone production in the testis. The aim of this paper is to outline the present status of the radiation treatment of CIS of the testis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Dose-dependent impairment of testicular function in patients treated with cisplatin-based chemotherapy for germ cell cancer.

BACKGROUND: The enormous differences in semen quality following cisplatin-based combination chemotherapy reported in previous studies may be caused by differences in the cisplatin dosages. PATIENTS AND METHODS: We examined thirty-three patients treated with conventional-dose PEB (cisplatin 20 mg/m2 x 5, q3w, etoposide 100 mg/m2 x 5 q3w and bleomycin 15 mg/m2 q1w) and 21 patients treated with high-dose PEB (cisplatin 40 mg/m2 x 5 q3w, etoposide 200 mg/m2 x 5 q3w and bleomycin 15 mg/m2 q1w). RESULTS: The sperm density was significantly higher (median 5.83 mill/ml) in the conventionally-treated group than in the group of high-dose-treated patients (median 0.005 mill/ml) (p = 0.008). Azoospermia was present in 19% of the conventionally- and in 47% of the high-dose-treated patients. All patients treated with a cumulative cisplatin dose above 600 mg/m2 had severe oligospermia or azoospermia. Serum values of basal follicle-stimulating hormone (FSH) (median 27.2 iu/l vs. 15.2 iu/l) and stimulated FSH (median 57.7 iu/l vs. 28.4 iu/l) were significantly higher in the high-dose group than in the conventionally-treated group. No differences could be detected in basal or stimulated testosterone or in luteinizing hormone in serum. CONCLUSION: In patients treated with PEB for testicular cancer, we found strong evidence that the impairment of spermatogenesis is dose-dependent.

Adolescent↗
PubMed1994

Ultrasonic texture and volume of testicles in infertile men.

Ultrasound scanning of the testes and surgical biopsy were performed in 95 infertile men to evaluate the use of ultrasound in male infertility. Ultrasonic testicular volume was calculated using three measurements and the formula of an ellipsoid, and the ultrasonic texture was evaluated and given a score from 1 to 5, indicating increasing degrees of irregularity. The median score was 3 (range 1-5), which was higher than previously found in normal men (median score 2; range 1-5; P < 0.0001). The ultrasonic texture score was lower in testes with a uniform pattern of 100% spermatogenic tubules compared with the rest, both for the right (P < 0.001) and for the left (P < 0.0005) testis. Texture score was correlated with the number of obliterated tubules for both testes (P < 0.001). The mean ultrasonic testicular volume of the right testis was 10.30 ml, and that of the left 10.26 ml. Both were smaller compared with the findings in normal men (P < 0.0001). Ultrasonic testicular volume was negatively correlated with texture score (P < 0.001). A positive correlation between ultrasonic volume and sperm count was seen (P < 0.001). Sperm count was negatively correlated with texture score if calculated together with data from 119 men from the general population (P < 0.001). The study shows that ultrasonic volume and texture are valuable parameters in the evaluation of infertile men.

Adult↗
PubMed1994

Insulin-like growth factor-I in celiac disease.

To contribute to the description of the physiopathological mechanisms of celiac disease, changes in insulin-like growth factor I (IGF-I) were followed-up in 21 children suspected of suffering from celiac disease. Thirteen children were suffering from celiac disease according to the original criteria of the European Society of Paediatric Gastroenterology and Nutrition. Ten celiac children changing from a gluten-containing to a gluten-free diet presented a significant rise in IGF-I (+1.54 mM per month). In a group of eight celiac children challenged with gluten, seven had a significant decrease in IGF-I (-1.11 mM per month), and five celiac children returning to the gluten-free diet after challenge with gluten had a marked but not significant increase in IGF-I (+1.7 mM per month). Eight children not suffering from celiac disease, but challenged with gluten, had a significant increase in IGF-I (+0.29 mM per month), corresponding to the expected age-dependent increase. The significant changes in IGF-I described under the diagnostic dietetic phases of celiac disease reflect the extent of growth retardation caused by the disease. IGF-I may be a supplementary aid in the diagnosis of celiac disease in describing individual changes under the dietetic phases.

Adolescent↗
PubMed1994

The value of quantitative DNA flow cytometry of testicular fine-needle aspirates in assessment of spermatogenesis: a study of 137 previously maldescended human testes.

In order to assess the suitability of DNA flow cytometry of fine-needle aspirates for quantifying spermatogenesis, the results from DNA flow cytometry were compared to histological evaluation of testicular biopsies taken concomitantly from 171 previously maldescended testes. In 137 of 171 cases, sufficient material for flow cytometric as well as histological evaluation was obtained. Histological analysis of surgical biopsy specimens revealed spermatogenesis including the spermatid stage in 117 of the 137 gonads. In six of the 117 gonads no haploid cells were found using flow cytometry. On the other hand, surgical biopsies failed to reveal spermatogenesis in five cases in which the corresponding aspirates contained haploid cells. Both methods therefore seem equally sensitive in detection of spermatogenesis. Other types of histological patterns also corresponded to distinct DNA histograms. Thus, in 11 of 12 cases with Sertoli-cell-only pattern in all tubules, at least 95% of the cells had a diploid DNA content. Furthermore, predominance of tubules with maturation arrest at the primary spermatocyte level corresponded to an increased proportion of tetraploid cells. When compared to surgical biopsy, DNA flow cytometry of testicular fine-needle aspirates is a more objective, easy and rapid method, which is more convenient for the patient. This study has indicated that DNA flow cytometry is a suitable method of quantitative assessment of spermatogenesis. One of the first target groups might be men with azoospermia. In such men, DNA flow cytometric analysis of fine-needle aspirates and surgical biopsy are apparently of equal sensitivity in detecting gonads with spermatogenesis. We conclude that DNA flow cytometry may become an alternative method for the quantification of spermatogenesis.

Adult↗
PubMed1993

Immunohistochemical expression of embryonal marker TRA-1-60 in carcinoma in situ and germ cell tumors of the testis.

BACKGROUND: Testicular cancer is preceded by the noninvasive stage of carcinoma in situ (CIS). According to a recent hypothesis, testicular CIA cells are germ cells transformed in fetal life. The idea of an embryonal origin of testicular germ cell neoplasia would be strengthened by the finding of antigenic similarity between fetal germ cells, CIS cells, and invasive testicular germ cell tumors. METHODS: Monoclonal antibody (MoAb) TRA-1-60 raised against a human embryonal carcinoma cell line was immunohistochemically tested on 21 fetal gonads (11 male gonads and 10 female gonads; 11th-24th week of gestation). In addition, TRA-1-60 was tested on tissue from 27 testes with CIS, 11 testes with invasive testicular cancer, and 24 adult and 4 infant testicular control specimens. RESULTS: Expression of TRA-1-60 was found in germ cells of six female and two male fetal gonads. In addition, 26 of 27 adult human testes with CIS, 7 of 8 seminomas, and 3 of 3 embryonal carcinomas were TRA-1-60 positive. CONCLUSIONS: The study demonstrated an antigenic link between fetal germ cells, cells of CIS and seminomas, and embryonal carcinomas. The results provided additional evidence for the hypothesis that testicular neoplasia arises during early fetal life and CIS cells are malignant fetal gonocytes.

Adult↗