Congenital iris ectropion and glaucoma associated with intestinal neuronal dysplasia: a manifestation of a neural crest syndrome.
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Biomedical subjects
Publications and source records attributed to Faruk Hadziselimovic.
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OBJECTIVE: To investigate the value of serum antitissue transglutaminase IgA antibodies (IgA-TTG) and IgA antiendomysial antibodies (IgA-EMA) in the diagnosis of coeliac disease in cohorts from different geographical areas in Europe. The setting allowed a further comparison between the antibody results and the conventional small-intestinal histology. METHODS: A total of 144 cases with coeliac disease [median age 19.5 years (range 0.9-81.4)], and 127 disease controls [median age 29.2 years (range 0.5-79.0)], were recruited, on the basis of biopsy, from 13 centres in nine countries. All biopsy specimens were re-evaluated and classified blindly a second time by two investigators. IgA-TTG were determined by ELISA with human recombinant antigen and IgA-EMA by an immunofluorescence test with human umbilical cord as antigen. RESULTS: The quality of the biopsy specimens was not acceptable in 29 (10.7%) of 271 cases and a reliable judgement could not be made, mainly due to poor orientation of the samples. The primary clinical diagnosis and the second classification of the biopsy specimens were divergent in nine cases, and one patient was initially enrolled in the wrong group. Thus, 126 coeliac patients and 106 controls, verified by biopsy, remained for final analysis. The sensitivity of IgA-TTG was 94% and IgA-EMA 89%, the specificity was 99% and 98%, respectively. CONCLUSIONS: Serum IgA-TTG measurement is effective and at least as good as IgA-EMA in the identification of coeliac disease. Due to a high percentage of poor histological specimens, the diagnosis of coeliac disease should not depend only on biopsy, but in addition the clinical picture and serology should be considered.
PURPOSE: Mini-puberty is the hormonal surge of gonadotropins and testosterone which occurs in early infancy. It induces the development and transformation of gonocytes into Ad spermatogonia, which is impaired in many cryptorchid testes. We examine the role of testosterone in the transformation and development of Ad spermatogonia. MATERIALS AND METHODS: A total of 32 patients 1 to 7 years old were treated with human chorionic gonadotropin (HCG) to achieve epididymo-testicular descent before orchiopexy (group 1), and 33 patients underwent orchiopexy without previous hormonal treatment (group 2). A testicular biopsy was obtained during surgery from all the patients. The number of Ad spermatogonia per tubular cross section (Ad/tbx) was assessed and compared between the 2 groups. The number of Ad spermatogonia per tubular cross section in group 1 was also correlated with the post-stimulatory testosterone plasma values. RESULTS: In group 1, 17 patients had greater than 0.1 Ad/tbx, and the remaining patients had 0.1 or less Ad/tbx. In group 2, 6 patients had greater than 0.1 Ad/tbx. Of the boys with cryptorchidism 35% responded inadequately to HCG stimulation, while 10% did not respond. Those patients with suboptimal Leydig cell capacity (and an inadequate response to HCG stimulation) had a defective Ad spermatogonia differentiation of 0.1 or less. CONCLUSIONS: Boys with cryptorchidism with an insufficient testosterone surge after HCG risk infertility despite early and successful surgery. The testicular biopsy assists in identifying those who might benefit from hormonal treatment following successful orchiopexy.
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BACKGROUND: The aim of this study was to describe the development of Ad spermatogonia in both unilateral and bilateral cryptorchid infants compared to a control population of comparable age and to note particularly the fate of Ad spermatogonia during the normal surge of testosterone and gonadotropin. METHODS: The incidence and development of Ad (dark) adult type of spermatogonia were assessed in 270 testicular biopsies from 159 cryptorchid infants at 1-12 months of age. These results were compared to the control population of the same age. RESULTS: The number of Ad spermatogonia increased markedly after five months of life in the control population. The scrotal testes of unilateral cryptorchid infants also had an increase in the number of Ad spermatogonia but it was distinctly lower than that of the control population. In contrast, this surge was completely absent in the cryptorchid testes. The number of Ad spermatogonia in unilateral cryptorchid testes correlated in a nonlinear fashion with those in the contralateral scrotal testes. The total number of germ cells in the cryptorchid testes in the first six months of life is normal, after which time it declines rapidly. CONCLUSION: The impaired transformation of germ cells into Ad spermatogonia in both unilateral and bilateral cryptorchid infant testes during mini-puberty underscores the importance of hypogonadotropic-hypogonadism in the pathogenesis of this disease.
The process of germ cell depletion in patients with Klinefelter syndrome (KS) is incompletely characterized. In the current work, we evaluated the presence of germ cells in adolescent boys with KS for possible future use in assisted reproduction techniques. Fourteen nonmosaic 47,XXY boys (aged 10-14 yr) were enrolled. Every fourth month their puberty was staged, and serum was obtained for hormone analyses. Each boy underwent a single testicular biopsy. Biopsy specimens of seven peripubertal boys (testicular volume < 2.0 ml) had spermatogonia of adult type, whereas older boys with larger testes (> 2.0 ml) exhibited no germ cells. No meiotic germ cells were detectable in any of these subjects. Depletion of germ cells was associated with an increase in testicular volume but was not immediately reflected in levels of serum gonadotropin, inhibin B, or anti-Müllerian hormone. In contrast, hypergonadotropism and suppression of serum inhibin B and anti-Müllerian hormone developed later, during midpuberty, after an unequivocal increase in serum testosterone (>2.5 nmol/liter) levels and degeneration of Sertoli cells. In conclusion, these prepubertal and early pubertal boys with KS had diploid germ cells that vanished in early puberty when testicular volume increased, whereas serum gonadotropin and inhibin B levels displayed pathological changes later during midpuberty.
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INTRODUCTION: The incidence of Ad spermatogonia (stem cells for fertility) was assessed in 20 cryptorchid patients, all of whom had a successful orchidopexy in childhood but developed azoospermia following puberty. MATERIALS AND METHODS: From a cohort of 231 patients who had a semen analysis following successful orchidopexy 20 patients (9%) had azoospermia. The patients were classified into 2 groups according to the time of surgery: A = < 21 months of age (n = 5, mean = 10.7 +/- 8.6 months) and B = during childhood (n = 15, mean = 10.1 +/- 3 years). Nine of the 20 patients (45%) had bilateral cryptorchidism: A = 1 and B = 8. Testicular biopsies were performed during orchidopexy and analyzed with semi-thin technique. The number of Ad spermatogonia and entire number of germ cells was determined. The patients' semen analyses were evaluated at least twice; FSH and testosterone plasma values were estimated. RESULTS: In group A, all patients had germ cells at the time of surgery (mean = 1.04 +/- 1.4 germ cells per tubular cross section); only 6 patients in group B (40%) had no germ cells (mean = 0.17 +/- 0.4); A vs. B, p = 0.0133. Importantly, Ad spermatogonia were absent in the entire study population. The plasma FSH of 16 patients (80%) was abnormal [median = 16.35 IU/L (Interquartile range of sample - IQR 9.075-27.85 95% CI, 3-53)] while the plasma testosterone of all the patients was normal. CONCLUSIONS: The most severe cause of infertility in cryptorchid patients cannot be mitigated by an early successful surgery alone.