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Biomedical subjects

F Hadziselimovic

Publications and source records attributed to F Hadziselimovic.

At least 37 records · Page 2Linked to original sources

Germ cell counts in semithin sections of biopsies of 115 unilaterally cryptorchid testes. The experience from the Children's Hospital of Philadelphia.

One hundred and fifteen biopsies from unilateral cryptorchid prepubertal patients were embedded in Epon. Semithin sections were examined by light microscope and the germ cell count per tubule was calculated. The mean number of germ cells was normal from birth to 12 months of age and dropped below the lower limits of normal between 1 and 2 years. Germ cell counts rose considerably during the 18-months observation period with the highest counts occurring in the last 6 months. Variability in the clinical diagnosis of cryptorchidism or inherent heterogeneity in the testicular histology of cryptorchidism are possible explanations.

Biopsy

Primary and secondary testicular atrophy.

1. (a) Primary and secondary testicular atrophy is caused by ischaemia, most frequently after intrauterine and prepuberal testicular torsion. (b) After standard orchiopexy, and especially after orchiopexy in high undescended testis, secondary testicular atrophy is frequent. (c) The histological condition of a cryptorchid testis does not predict atrophy. Immediate detorsion and/or prophylactic fixation as well as subtle technique in orchiopexy are essential. 2. Sympathetic orchiopathy of a unilateral atrophic testis was not proven in cryptorchidism and testicular torsion. There is considerable evidence of primary bilateral disease. 3. Testicular atrophy as an aetiological factor in the development of testicular tumor remains open to debate.

Atrophy

Treatment of cryptorchidism with low doses of buserelin over a 6-months period.

In a collaborative study, 48 prepubertal boys with undescended testes ranging in age from 15 months to 11 years were treated with low-dose intranasal buserelin following an every-other-day programme for a period of 6 months. Urinary LH, FSH, and testosterone were not altered during the treatment period. Boys over 7 years of age experienced a slight but significant rise in testosterone at the end of treatment. Testicular descent was achieved in only 17% of boys. In the remainder, bilateral testicular biopsies were obtained during orchiopexy. Grouped analysis showed a significant increase in the number of germ cells per tubule in both unilateral and bilateral cryptorchid boys, suggesting that buserelin treatment of the testis in a cryptorchid position is capable of improving fertility potential. If time-matched controls are compared to treated boys of the same age, again a significant difference is observed indicating that buserelin treatment does increase the germ cell count.

Administration, Intranasal

Screening for cryptorchid boys risking sterility and results of long-term buserelin treatment after successful orchiopexy.

This long-term prospective follow-up study showed that in cryptorchid patients a significant correlation exists between the number of germ cells at the time of orchiopexy (prepuberty) and the spermiogram, and thus a biopsy has a prognostic value. Fifty percent of our patients had a germ cell count of less than 0.1 per tubule and belong to the risk group for sterility. Successful surgery could not induce a significant increase of germ cells in the risk group, although it does prevent secondary testicular damage. Patients with cryptorchidism developed after birth have significantly better chances of fertility than those with primary cryptorchidism. The priming effect of testosterone in the first months of life is important for male fertility. In patients belonging to the risk group treated with buserelin, a significant age-dependent increase in germ cell count occurred.

Adult

Omphalocele, cryptorchidism, and brain malformations.

Nineteen male infants died with a large omphalocele and 52% had associated cryptorchidism. However, two different groups with both omphalocele and cryptorchidism were recognized: (1) Eleven patients with omphalocele without brain malformation and an incidence of undescended testes not significantly different from the normal population; (2) Eight patients with omphalocele and brain malformation all having cryptorchidism. A comparison of the groups indicated that intact intraabdominal pressure during intrauterine life is not a main driving force of testicular descent, whereas normal testicular descent may occur only when the brain is normally developed. Whenever a child with omphalocele and cryptorchidism is examined, careful evaluation of the central nervous system is indicated. This triad of malformations may have prognostic and therapeutic implications.

Brain

Autoimmune phenomena and cytogenetic findings in a patient with carcinoma (seminoma) in situ.

Routine examination of a testis biopsy from a patient with oligospermia and a large varicocele in his left testicle and who was childless for over 2 years showed carcinoma in situ (CIS) with atypic spermatogonia in his right testicle. Immunohistochemical investigations of this tissue revealed large intracellular deposits of immunoglobulin G (IgG) restricted to the atypical cells. By blot-immunobinding test of the patient's serum, circulating antibodies against a molecule with an approximate molecular weight of 60 kD were found. Such antibodies were not found in a total of over 500 infertile patients and fertile controls examined. This molecule was extracted from pooled normal human sperms by trypsin digestion and eluted out of a sodium dodecyl-sulphate polyacrylamide gel (SDS-PAGE). This elute is currently used for raising monoclonal antibodies. An analysis of the direct chromosome preparations from the testis biopsy showed both numerical and structural chromosomal aberrations. This might indicate that the atypical cells have already been transformed and hence could be considered as malignant.

Adult

The value of testicular biopsy in patients with varicocele.

With the use of semi-thin sections of 88 testicular biopsies from 44 patients, we were able to separate a relatively uniform group of patients with idiopathic left varicocele and infertility into 4 groups with different pathophysiological conditions. Group 1 patients had atrophy of the Leydig cells, decreased Leydig cell ratio, low plasma testosterone, and normal luteinizing and follicle-stimulating hormone levels. Surgery resulted in a significant improvement in sperm count. Group 2 patients had undergone attempted repair of Leydig cells, and had a normal Leydig cell ratio, and normal testosterone, luteinizing hormone and follicle-stimulating hormone plasma values. Group 3 patients demonstrated hyperplasia and an increased Leydig cell ratio, high luteinizing and follicle-stimulating hormone values, and relatively high testosterone values. Group 4 patients had an increased Leydig cell ratio but severe atrophy of the Leydig cells and tubuli, indicating burned out testes with high luteinizing and follicle-stimulating hormone but low testosterone levels. A successful operation failed to increase the sperm count in the latter groups. The technique used should allow better patient selection for medical treatment, as well as lead to a better understanding of the etiopathogenesis of infertility in varicocele patients. Therefore, the histological technique has an important role in the evaluation of patients suffering from infertility in general.

Adolescent

[Cryptorchism].

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Chorionic Gonadotropin

[Timing of therapy of cryptorchidism].

Dysfunctions of the endocrine glands are among the most prominent causes of cryptorchidism. Whereas all gonads show spermatogonia during the first to sixth months of life, loss of spermatogonia is seen in 25% of children with unilateral cryptorchidism already in the second year of life. A randomised study revealed decreased in gonadotropin reserves which was more marked after unsuccessful treatment than after successful therapy. In 119 treated children, the quota of descended testicles was between 47 and 55%. Ultrastructurally, LH-RH exercises an action on Leydig's cells. Treatment should be initiated already in the first year of life. LH-RH is recommended as the first conservative treatment. If this is not successful, additional administration of chorionic gonadotropin (HCG) can achieve descent in an additionally high percentage of cases.

Age Factors

Effect of LH-RH treatment on hypothalamo-pituitary-gonadal axis and Leydig cell ultrastructure in cryptorchid boys.

62 cryptorchid boys aged 2-6 years were selected at random either for surgical or for hormonal LH-RH treatment. As all biopsies from boys operated show typical histological and ultrastructural signs of cryptorchidism, it can be concluded that only true cryptorchid patients are included in our study. LH-RH treatment was successful in 16 (55%) of 31 boys. Median 30-min response values to LH-RH test of LH were initially normal in all boys. Those treated successfully remain normal after treatment whereas unsuccessfully treated patients have significantly lower LH 30-min response values at the end of the 4 weeks of LH-RH treatment. FSH response was not statistically different before or after treatment. This might indicate that a normal LH response is necessary for testicular descent. In the 15 boys operated after 4 weeks of unsuccessful LH-RH treatment, testes biopsies show recruitment of the Leydig cell precursors and development of juvenile Leydig cells with an increase in their content of lipoid droplets and smooth endoplasmic reticulum. No adverse effect on the number of spermatogonia could be observed after 4 weeks of LH-RH treatment.

Biopsy

Pathogenesis of cryptorchidism.

Cryptorchidism was induced experimentally by treating pregnant mice on the 14th day of pregnancy with 5 mg estrogen. Testes from cryptorchid and control newborn and adult mice were investigated with radioimmunoassay and electron microscopy. It was concluded that a normal Leydig cell function plays a decisive role in testicular descent. In cryptorchidism, Leydig cells at birth are atrophic. Testicular testosterone content is diminished as compared to controls. Ultrastructural alterations of Leydig cells observed in our experiments closely resemble those found in biopsies of cryptorchid patients. In male mouse offspring, prenatal estrogen injection induced not only a cryptorchidism but also Leydig cell atrophy and a permanently impaired function. Testosterone content is still significantly diminished after puberty. It is proposed therefore that an insufficiency of endocrine gonadal function of hypothalamo-pituitary origin occurring during intrauterine development is one of the main causes of cryptorchidism. An appropriate long-term therapy could diminish the high sterility rate.

Age Factors

The meaning of the Leydig cell in relation to the etiology of cryptorchidism: An experimental electron-microscopic study.

In our electron-microscopic studies of testicular biopsies, both normal and cryptorchid, we found a simple atrophy of the Leydig cell in the cryptorchid testis. Based on experiments by Raynaud1,2 and Jean3 on pregnant mice, we tried to find the reason for changes in the Leydig cell relating to the etiology of cryptorchidism. We found on electron microscopic study of testes in the offspring of pregnant mice treated with estrogen the same atrophy of the Leydig cell as we see in human cryptorchidism. These changes are not evident when estrogen and HCG are given together. We can conclude from this experiment that lack of gonadotropin stimulation leads to the atrophy of Leydig cells. This atrophy then produces a lack of androgen which could be responsible for cryptorchidism.

Androgens