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Biomedical subjects

P M Petersen

Publications and source records attributed to P M Petersen.

At least 19 recordsLinked to original sources
PubMed2000

Cryopreservation of semen from pubertal boys with cancer.

BACKGROUND: The possibility of cryopreservation of semen from adolescents has until now received only little attention. Therefore, we have investigated the possibility of cryopreservation of semen in adolescent boys with cancer. PROCEDURE: Forty-five boys, aged 13-18 years, admitted because of cancer during the period January 1, 1995 to July 31, 1998 were eligible. Semen was obtained after masturbation in the majority of the cases. In three boys, semen was preserved after penile vibration or electroejaculation in general anaesthesia. The semen samples were analysed for concentration, motility, and morphology according to the WHO guidelines. The sample was transferred into straws prior to cryopreservation at 196 degrees C in liquid nitrogen. RESULTS: Twenty-one boys delivered a semen sample for cryopreservation. Four boys were offered and accepted sperm banking but were not able to produce a sample. In 20 cases time did not allow an attempt of sperm banking, the boy was not assessed to be mature enough to deliver a semen sample, or the procedure was not accepted. The boys delivered 1-3 samples, and the total number of spermatozoa ranged from 0-210 millions. Median percentage of motile sperm was 50% (range 9-86%). Semen quality improved with age; however, a 13- year- old boy produced 75 million spermatozoa with 38% motile cells. CONCLUSIONS: Pubertal maturation should be assessed in all boys admitted for cancer, and the possibility of sperm banking should be discussed with the patient and his parents.

Adolescent↗
PubMed2000

Reproductive function in male rats after brief in utero exposure to diethylstilboestrol.

Long-term effects of brief in utero exposure to diethylstilboestrol (DES) during a foetal period known to be critical for gonadal development were evaluated. Rats were exposed to DES (100 microg/kg body-weight) from day 17 to 19 of pregnancy. All of the DES-treated pregnant rats (11/11) ate parts or whole of their offspring during the first day after birth (p=0.03). Surviving male offspring were examined on day 63 post-partum. DES induced a reduction in weight of the testis (p=0.06) and ventral prostate (p=0.07), even after this short exposure. DES tended to reduce the number of Sertoli cells (p=0.13). Our findings indicate that even a short in utero exposure of rats to DES during a critical period for gonadal development results in cannibalism and reduced testis and ventral prostate weight.

Animals↗
PubMed2000

Cancer and male infertility.

An increasing proportion of boys and young men with cancer will survive their disease and desire fertility. Unfortunately, the cancer treatment, and in some cases the malignant disease itself, may have a negative and permanent impact on the individual's fertility potential. This effect is highly dependent on the type and dose of therapy as well as the age at which it has been given. Basic knowledge in this field is necessary to enable oncologists and fertility specialists to counsel these patients about their fertility prospects and, if appropriate, advise them to take precautions (e.g. the cryopreservation of semen) to safeguard their fertility. Another aspect of the relationship between cancer and infertility is the possibility that men with testicular dysfunction may have an increased risk of testicular cancer. Screening for early testicular malignancy may therefore be advisable in some groups of men with poor semen quality.

Antineoplastic Agents↗
PubMed1999

The course of long-term toxicity in patients treated with cisplatin-based chemotherapy for non-seminomatous germ-cell cancer.

BACKGROUND: The prognosis of advanced testicular cancer has improved considerably after the introduction of cisplatin-based combination chemotherapy. The improved prognosis of testicular cancer has brought the long-term toxicity of the treatment into focus. PATIENTS AND METHODS: Long-term toxicity was investigated prospectively until more than 10 years after after treatment in a group of 22 patients treated with six series of cisplatin based chemotherapy (PVB) for testicular cancer. We have focused on nephro-, neuro-, pulmonary-, and gonadal toxicity. RESULTS: Glomerular filtration rate (GFR) decreased significantly during treatment but increased during follow-up and all the patients had normal values of GFR 10-15 years after treatment. Carbon monoxide diffusion capacity (TLco) decreased during PVB treatment in smokers. TLco remained unchanged during the first years after PVB treatment, but improvement of TLco was seen in some patients more than 43 months after treatment. Paresthesia was reported by 83% of the patients immediately after treatment, 50% at follow-up 4-9 years after chemotherapy and 14% prevalence 11-15 hears after treatment. The reported decline in neurotoxicity was verified by normalisation of vibration perception. Gonadal toxicity was severe and persistent although improvement was seen in a few patients even many years after treatment. CONCLUSIONS: The patients treated with PVB were physically and socially well-being at follow-up investigation 11-15 years after treatment. Improvements in pulmonary- and renal function, and recovery from neurotoxicity was seen during the long-term follow-up period. Gonadal toxicity was severe and persistent.

Adolescent↗
PubMed1999

Impaired testicular function in patients with carcinoma-in-situ of the testis.

PURPOSE: To elucidate the biologic association between germ cell neoplasia and testicular dysfunction, through investigation of Leydig cell function and semen quality in men with carcinoma-in-situ (CIS) of the testis. PATIENTS AND METHODS: We examined two groups of men, unilaterally orchidectomized for testicular cancer. Biopsy of the contralateral testis had showed CIS in a group of 24 patients and no evidence of CIS in the other group of 30 patients. Semen quality and serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were compared in these two groups of men after orchidectomy but before further treatment for testicular cancer. RESULTS: Significantly higher LH levels (median, 8.1 IU/L v 4.8 IU/L; P < .001) and generally lower testosterone levels (median, 12.5 nmol/L v 15.5 nmol/L; P = .13) were found in the CIS group. The proportion of patients with Leydig cell dysfunction was higher in the group of patients with CIS (11 of 24) than in the group of patients without (two of 30) (P = .01). Sperm concentration and total sperm count were significantly lower (P < .001) in patients with CIS (median, 0.03 x 10(6)/mL and 0.10 x 10(6), respectively) than in patients without (median, 9.1 x 10(6)/mL and 32 x 10(6), respectively), whereas the levels of FSH were significantly higher (P < .001) in the former group of men (median, 19.6 IU/L v 9.0 IU/L). CONCLUSION: Not only spermatogenesis but also Leydig cell function is impaired in testes with CIS. This impairment could be due to common factors in the pathogenesis of germ cell neoplasm and testicular dysfunction. Alternatively, CIS cells may have a negative impact on Leydig cell function.

Adult↗
PubMed1999

Semen quality and reproductive hormones before orchiectomy in men with testicular cancer.

PURPOSE: To obtain information about preorchiectomy gonadal function in patients with testicular germ cell cancer to improve the clinical management of fertility and other andrologic aspects in these men. PATIENTS AND METHODS: In group 1, a group of 83 consecutive patients with testicular germ cell cancer (TGCC) investigated before orchiectomy, semen analysis was carried out in 63 patients and hormonal investigations, including measurement of follicle-stimulating hormone, luteinizing hormone (LH), testosterone, estradiol, sex hormone-binding globulin (SHBG), inhibin B, and human chorionic gonadotropin (hCG), in 71 patients. Hormone levels in patients with elevated hCG (n = 41) were analyzed separately. To discriminate between general cancer effects and specific effects associated with TGCC, the same analyses were carried out in a group of 45 consecutive male patients with malignant lymphoma (group 2). Group 3 comprised 141 men employed in a Danish company who served as controls in the comparison of semen parameters. As a control group in hormone investigations, 193 men were selected randomly from the Danish National Personal Register to make up group 4. RESULTS: We found significantly lower sperm concentration (median, 15 x 10(6)/mL; range, 0 to 128 x 10(6)/mL) and total sperm count (median, 29 x 10(6)/mL; range, 0 to 589 x 10(6)) in patients with testicular cancer than in patients with malignant lymphomas (sperm concentration: median, 48 x 10(6)/mL; range, 0.04 to 250 x 10(6)/mL; sperm count: median, 146 x 10(6); range, 0.05 to 418 x 10(6)) (P < .001 and P < .001) and healthy men (sperm concentration: median, 48 x 10(6)/mL; range, 0 to 402 x 10(6)/mL; sperm count: median, 162 x 10(6); range, 0 to 1253 x 10(6)) (P < .001 and P < .001). FSH levels were increased in men with testicular cancer (median, 5.7 IU/L; range, 2.0 to 27 IU/L) compared with both men with malignant lymphomas (median, 3.3 IU/L; range, 1.01 to 12.0 IU/L) and healthy controls (median, 4.1 IU/L; range, 1.04 to 21 IU/L)(P = .001 and P = .007, respectively). Surprisingly, we found significantly lower LH in the group of men with TGCC (median, 3.6 IU/L; range, 1.12 to 11.9 IU/L) than in healthy men (median, 4.7 IU/L; range, 1.3 to 11.9 IU/L) (P = .01). We could not detect any differences between men with testicular cancer and men with malignant lymphomas and healthy men with regard to serum levels of testosterone, SHBG, and estradiol. Men with testicular cancer who had increased hCG levels had significantly lower LH and significantly higher testosterone and estradiol than those without detectable hCG levels. CONCLUSION: Spermatogenesis is already impaired in men with testicular cancer before orchiectomy. Neither local suppression of spermatogenesis by tumor pressure nor a general cancer effect seems to fully explain this impairment. The most likely explanation is preexisting impairment of spermatogenesis in the contralateral testis in men with testicular cancer. The question of whether also a pre-existing Leydig cell dysfunction is present in men with testicular cancer could not be answered in this study because the tumor seems to have a direct effect on the Leydig cells. Men with testicular cancer had low LH values as compared with controls. We speculate that increased intratesticular level of hCG also in men without measurable serum hCG may play a role by exerting LH-like effects on the Leydig cells, causing increased testosterone and estrogen levels and low LH values in the blood.

Adult↗
PubMed1999

Undetectable inhibin B serum levels in men after testicular irradiation.

A group of men treated with testicular irradiation for carcinoma in situ in the remaining testis after orchidectomy for unilateral testicular germ cell cancer was used as a model to study of the effect of selective eradication of germ cells on the levels of serum inhibin B in the human male. Thirteen men with verified spermatogenesis and detectable preirradiation levels of serum inhibin B (median, 55; range, 23-193 pg/mL) were investigated before and after testicular irradiation (14-20 Gy). All patients had undetectable levels of inhibin B 2-12 months (median, 5 months) after radiotherapy (<20 pg/mL). Correspondingly, serum FSH increased in all men after radiotherapy [from a median of 9.6 (range, 3.0-24) IU/L to a median of 28 (range, 15-70) IU/L); P < 0.001]. Histological investigation showed a Sertoli cell-only pattern in all patients after radiotherapy. Neither LH nor testosterone showed a significant decrease after radiotherapy. Our data indicate that inhibin B production sufficient to maintain detectable serum levels in adults requires spermatogenic activity.

Adult↗
PubMed1999

Semen quality and reproductive hormones before and after orchiectomy in men with testicular cancer.

PURPOSE: We clarify the impact of removal of the tumor bearing testis on semen quality and reproductive hormones in men with testicular cancer. MATERIALS AND METHODS: Semen quality and levels of reproductive hormones were investigated in 48 men before and after orchiectomy for testicular cancer. Semen analysis was done in 35 of these men and hormone analyses were done in 47. The hormone data of patients with (14) or without (33) elevated values of human chorionic gonadotropin (HCG) were analyzed separately. RESULTS: Median sperm concentration and total sperm count decreased from 17 x 10(6)/ml. (range 0 to 117) and 39 x 10(6) (0 to 433), respectively, before to 7 x 10(6)/ml. (0 to 69) and 30 x 10(6) (0 to 200), respectively, after orchiectomy. After orchiectomy sperm concentration was decreased in 30 of 35 men (p = 0.001) and azoospermia developed in 3 (9%). In men without detectable HCG median follicle-stimulating hormone levels increased (p <0.001) from 5.7 IU/l. (range 0.01 to 30) before to 10.0 IU/l. (4.6 to 48) after orchiectomy in 33 of 33 patients. Median inhibin B significantly decreased (p = 0.003) from 108 pg./l. (range 60 to 193) before to 95 pg./l. (less than 20 to 141) after orchiectomy. Median luteinizing hormone increased significantly from 3.1 IU/l. (range 1.1 to 9.9) before to 5.2 IU/l. (2.1 to 27) after treatment (p <0.001). Testosterone and sex hormone-binding globulin did not change significantly after orchiectomy. Patients with detectable serum HCG before orchiectomy had a considerable increase in follicle-stimulating hormone after orchiectomy, and a concomitant decrease in testosterone and estradiol. CONCLUSIONS: Semen quality was poor at diagnosis and deteriorated further after orchiectomy compared with pretreatment values. Our findings indicate that in some patients the most appropriate time for cryopreservation of semen is before orchiectomy. Androgen production was maintained by increased luteinizing hormone stimulation after orchiectomy.

Adult↗
PubMed1998

Germ cell cancer and disorders of spermatogenesis: an environmental connection?

Why is there a small peak of germ cell tumours in the postnatal period and a major peak in young age, starting at puberty? And, paradoxically, small risk in old age, although spermatogenesis is a lifelong process? Why is this type of cancer more common in individuals with maldeveloped gonads, including undescended testis, gonadal dysgenesis and androgen insensitivity syndrome? Why has there, during the past 50 years, been a quite dramatic increase in testicular cancer in many developed countries? These are just a few of many questions concerning testicular cancer. However, the recent progress in research in the early stages of testicular cancer (carcinoma in situ testis (CIS)) allows us to begin to answer some of these questions. There is more and more evidence that the CIS cell is a gonocyte with stem cell potential, which explains why an adult man can develop a non-seminoma, which is a neoplastic caricature of embryonic growth. We consider the possibility that CIS cells may loose their stem cell potential with ageing. Along these lines, a seminoma is regarded a gonocytoma where the single gonocytes have little or no stem cell potential. The Sertoli and Leydig cells, which are activated postnatally and during and after puberty, may play a crucial role for both the development of the CIS gonocyte and progression of the neoplasm to invasiveness. The reported increase in testicular cancer is not the only sign that male reproductive health is at risk. There are reports that undescended testis and hypospadias have become more common. Also semen quality has deteriorated, at least in some countries. The epidemiological evidence suggests that environmental factors may play a role. Are the environmental hormone disrupters (e.g. DDT, PCB, nonylphenol, bisphenol A) to be blamed for the apparently synchronised deterioration in these aspects of male reproductive health?

Adult↗
PubMed1998

Gonadal function in men with testicular cancer: biological and clinical aspects.

This paper reviews current knowledge about the effect of testicular germ cell cancer (TGCC) on gonadal function and of cancer treatment on spermatogenesis and Leydig cell function. It is well documented that testicular cancer is associated with impaired spermatogenic function and some patients already have impairment of Leydig cell function before orchidectomy. The degree of spermatogenic dysfunction is higher than what can be explained by local tumour effect and by a general cancer effect, since patients with other malignant diseases have normal, or only slightly decreased, semen quality. Furthermore, sperm counts after orchidectomy are further reduced to less than half of the values in healthy men, even in patients cured from the cancer disease after orchidectomy alone. These observations are supported by histological investigations which have shown a high prevalence of abnormalities of spermatogenesis in the contralateral testis in patients with unilateral TGCC. The association between testicular cancer and poor gonadal function is very interesting both from a biological and from a therapeutic point of view. Firstly, the increase in incidence of testicular cancer has been suggested to be associated with a general decline in male reproductive health and it seems likely that the development of TGCC shares common aetiologic factors with development of other types of testicular dysfunction. This suggestion is supported by the observation that men with various types of gonadal dysfunction such as testicular dysgenesis, androgen insensitivity syndrome, and cryptorchidism have increased risk of testicular cancer. Secondly, the general cure rate in patients with testicular cancer exceeds 90% and the quality of life, including fertility aspects, is therefore important in the management of these patients. Spermatogenesis is already so severely impaired before treatment that fertility is lower than in healthy men. Moreover, radiotherapy and chemotherapy both induce dose-dependent impairment of spermatogenesis and recovery of spermatogenesis after treatment may be long lasting even more than five years in some patients. Sufficient androgen production is seen in the majority of the patients, but some patients suffer from testosterone deficiency. The effect of chemotherapy on Leydig cell function also seems to be dose-dependent. In conclusion there is no doubt that testicular cancer is associated with poor gonadal function even before treatment. Furthermore, the treatment of testicular cancer may have a serious impact on the gonadal function in these patients, most of whom are in the reproductive age. Moreover, the epidemiological and clinical data indicate a common aetiology between testicular germ cell cancer and other abnormalities in male reproductive health (such as infertility and cryptorchidism). These observations are in agreement with the suggestions of hormonal involvement in the aetiology of testicular cancer. Generally, men with TGCC need counselling about their reproductive function with respect to semen cryopreservation, chance of recovery of spermatogenesis, fertility, and the possible need for androgen replacement.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Gonadal function in men with testicular cancer.

This article reviews current knowledge on the effect of testicular germ cell cancer (TGCC) on gonadal function and of the cancer treatment on spermatogenesis and Leydig cell function. It seems likely that development of TGCC shares common etiological factors with development other types of testicular dysfunction. This suggestion is supported by the observation that men with various types of gonadal dysfunction such as testicular dysgenesis, androgen insensitivity syndrome, and cryptorchidism have increased risk of testicular cancer. Epidemiological and clinical data indicate common etiology between testicular germ cell cancer and other abnormalities in male reproductive health such as infertility and cryptorchidism. These observations are in agreement with the suggestions of hormonal involvement in the etiology of testicular cancer. It is well documented that testicular cancer is associated with impaired spermatogenic function and some patients have impairment of Leydig's cell function already before orchidectomy. The degree of spermatogenic dysfunction is higher than what can be explained by local tumor effect and by a general cancer effect. These observations are supported by histological investigations, which have shown a high prevalence of abnormalities of spermatogenesis in the contralateral testis in patients with unilateral TGCC. The spermatogenetic function is still severely impaired after orchidectomy and radiotherapy as well as chemotherapy induce further dose-dependent impairment of spermatogenesis. Recovery of spermatogenesis after treatment may be long, in some patients lasting more than 5 years. Sufficient androgen production is seen in the majority of the patients but some patients do suffer from testosterone deficiency. The effect of chemotherapy on Leydig's cell function seems to be dose dependent. Trials on protection of spermatogenetic function against the harmful effects of radiotherapy and chemotherapy by suppression of spermatogenesis has not been successful. The only way to maintain fertility is to limit gonadal exposure to harmful agents. Moreover cryopreservation of semen should be done before treatment. The optimal time for cryopreservation is before orchiectomy at least in some patients. Generally men with TGCC need counselling about their reproductive function, with respect to semen cryopreservation, chance for recovery of spermatogenesis, fertility, and the possibility of need for androgen replacement.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Testicular carcinoma in situ detected by ultrasound in infertile men].

The findings of non-palpable testicular tumour and contralateral carcinoma in situ testis (CIS) in two men, examined because of infertility, are described. Both patients had no symptoms other than infertility and bilateral testicular atrophy. Ultrasonography showed tumour in both cases and abnormal ultrasonic texture of testicular tissue in the contralateral testis. Both patients had seminomas and contralateral CIS. These cases show the value of ultrasonic examination of testis in men examined for infertility, and ultrasonic examination is recommended in these men, particularly if they have testicular atrophy.

Adult↗
PubMed1997

Detection of chromosomal aberrations in seminomatous germ cell tumours using comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to evaluate tissue specimens from 16 seminomas in order to elucidate the pathogenesis of germ cell tumours in males. A characteristic pattern of losses and gains within the entire genomes was detected in 94% of the seminomas by comparing the ratio profiles of the tumours with a standard of cytogenetically normal genomic DNA. Losses represented 43% of the total number of alterations often affecting chromosomes and chromosome arms 4, 5, 11, 13q, and 18q. Gains amounted to 57% and were often observed on 1q, 7, 8, 12, 14q, 15q, 21q, and 22q. Aberrations of 12p and 21q appeared most consistently. Results from CGH analysis displayed no relationship to the clinical stages of the malignancy. Some rare aberrations appeared, however, only in clinical stage II and in tumours showing relapse in the contralateral testis following orchiectomy, although the alterations were not present in all of the tumours in question. Losses of 16q13-21 and gains of 9q22.1-22.2 were demonstrated in both groups, while loss of 16p12 and gains of 6p21 and 6q23.3-24 were detected in the latter group as well. In conclusion, a specific pattern of chromosomal alterations was demonstrated in the seminomas by improved detection criteria, which increased specificity and sensitivity. The rare aberrations, which appeared only in tumours in improved detection criteria, which increased specificity and sensitivity. The rare aberrations, which appeared only in tumours in clinical stage II and relapsed tumours, may be linked to tumour progression, invasiveness, and bilateral disease.

Chromosome Aberrations↗
PubMed1996

Synthesis of heterocycles containing two cytosine or two guanine base-pairing sites. Novel tectons for self-assembly.

The synthesis of 1 and 2 is described, as is the X-ray structure of 1. Tecton 1 contains two DAA hydrogen bonding sites (cytosine-like), while 2 contains two DDA sites (guanosine-like). Tectons 1 and 2 were designed to self-assemble into a helical superstructure. Self-recognition of 1 occurs in the solid state with a novel inclusion of dimethylacetamide solvent.

Crystallography, X-Ray↗
PubMed1995

Concurrence of high levels of interferons alpha and beta in cord and maternal blood and simultaneous presence of interferon in trophoblast in an African population.

A high concentration of interferon-alpha (IFN-alpha) (> 5 U/ml) in cord blood was used as the criterion for establishing our study group. In a collection from deliveries by 269 Kenyan women, 16 such cord samples with matching maternal blood and placental biopsies were identified. These 16 were studied in detail together with 23 randomly selected among those with low cord IFN-alpha levels. The levels of IFN- in retal blood correlated with levels in their mothers for both IFN-alpha and beta but not for IFN-gamma. IFN-alpha was furthermore demonstrated in villous and decidual trophoblast from 15 (94%) placentae from donors with high IFN-alpha in the cord blood but not in the placenta of any low IFN level donors. In contrast, IFN-beta was not demonstrated in any placenta. These observations suggest simultaneous IFN induction in the three compartments, transplacental IFN transport, or trophoblast production of IFN to both circulations. Looking for IFN inducers, we did serologic tests for nonspecific indicators of inflammation and for specific virus and protozoan infections, but these showed no relation to elevated IFN levels. Immunohistology also revealed no evidence of a number of placental infections. The cause of the high levels of IFN-alpha could still be infectious but remains unexplained and may be noninfectious.

Biopsy↗
PubMed1994

Human trophoblast interferons enhance major histocompatibility complex class I antigen expression on human term trophoblast cells in culture.

The expression and regulation of major histocompatibility complex class I (MHC class I) antigens by virus-induced human trophoblast interferons (tro-IFNs) were examined in term trophoblast cultures. Flow cytometry studies using fluorescence monoclonal antibodies against MHC class I antigens revealed that isolated cytotrophoblasts can express MHC class I antigens. The expression of these antigens increased with stimulation of trophoblast cultures with tro-IFN-alpha and -beta. One hundred IU tro-IFN-alpha and -beta/ml induced no significant higher levels of MHC class I antigens as compared with the control, whereas 1000 IU tro-IFN-alpha and -beta/ml did. The tro-IFN-enhanced expression of MHC class I antigens may be important as it increases the efficiency of local and viral antigen presentation, cytotoxicity by T cell response and local inflammatory processes, thereby preventing virus spread from mother to fetus.

Cells, Cultured↗