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Biomedical subjects

F Hadziselimovic

Publications and source records attributed to F Hadziselimovic.

At least 19 recordsLinked to original sources

Hypoplasia of the corpus callosum and growth hormone deficiency in the XXXXY syndrome.

A 3-year-old Libyan boy with the XXXXY syndrome is described. MRI examination of the brain showed hypoplasia of the corpus callosum. He had growth retardation and endocrine studies demonstrated growth hormone (GH) deficiency. Dermatoglyphic pattern was different from previous reports. At histological examination of the undescended testes, Leydig cells were seen although they are usually not found in this variant of the Klinefelter syndrome.

Agenesis of Corpus Callosum

Buserelin treatment of cryptorchidism: a randomized, double-blind, placebo-controlled study.

The objectives of the study were to determine whether a low dose of a luteinizing hormone-releasing hormone analogue (buserelin) has an effect on testicular descent, if buserelin affects germ cell maturation and epididymal development, the incidence of retractile testes in the controlled trials, and if the subsequent administration of human chorionic gonadotropin has any effect on the groups treated. The study was double blind, placebo controlled in which patients with cryptorchidism were assigned randomly into 3 groups: buserelin treatment (22), surgical treatment (18) or placebo control group (19). The 3 groups of patients were similar before treatment in regard to testicular position, chronological and bone age, height and weight, luteinizing hormone, follicle-stimulating hormone, testosterone, penile size and the volume of the contralateral testis. Buserelin (20 micrograms). administered daily in a nasal spray significantly induced testicular descent compared to the group treated with a placebo (p less than 0.01). A normal epididymis was found more often in boys with successful descent (p less than 0.003). Boys treated with buserelin had the highest number and the best maturation index of the germ cells; human chorionic gonadotropin influenced the descent in both groups but it was more efficacious when it was administered after treatment with buserelin, although it had no additional effect on germ cell maturation. None of the boys had retractile testes. Buserelin was capable of inducing testicular descent in addition to increasing simultaneously the number of germ cells and provoking further development of the epididymis.

Child

Is a testis located at the superficial inguinal pouch (Denis Browne pouch) comparable to a true cryptorchid testis?

In a clinical study 96 prepubertal boys with 100 testes located in the superficial inguinal pouch underwent routine orchiopexy. Of 65 patients 45 (69%) who had received hormonal treatment before the surgical procedure had a closed processus vaginalis compared with only 11 of 35 (31%) who had not (p less than 0.0002). A normal epididymis was also present significantly more often in those patients receiving hormonal treatment than in those who did not (p less than 0.039). While those testes located in the superficial inguinal pouch had significantly better histology and a greater number of germ cells than those located in a high inguinal or abdominal position (p less than 0.01), the number of germ cells per tubule was nonetheless lower than that seen in the normal controls (p less than 0.01). In conclusion, a testis located at the superficial inguinal pouch behaves as a true cryptorchid testis. Furthermore, hormonal treatment before surgery has a significant effect on epididymal development and closure of the processus vaginalis.

Adolescent

An absent testis is associated with contralateral testicular hypertrophy.

Surgical exploration was done in 109 boys ages birth through 9 years with unilateral impalpable testes by physical examination under anesthesia. Of the patients 51 (47%) had an absent testis and 58 had intra-abdominal testes. At open biopsy of the contralateral descended testis the 3 dimensions of the exposed testis were recorded and testicular volume was calculated. The mean volume of the contralateral descended testes of boys with an absent testis was greater than that of boys with intra-abdominal testes at all ages. The differences were significant (p = 0.0019 to 0.0117) from birth through year 4 but not from years 5 through 9. However, the standard deviations ranged from 27 to 74% of the means, and there was broad overlap of the volumes of the 2 groups. These findings indicate that, although the volume of the contralateral descended testis of boys with an absent testis is significantly greater than that of boys with intra-abdominal testes, the volume of the contralateral descended testis is not a reliable criterion for differentiating an absent testis from an intra-abdominal testis in a boy with a unilateral impalpable testis. Surgical exploration continues to be the method of choice for making the diagnosis of an absent testis.

Adaptation, Physiological

Occurrence of large granular lymphocytes and natural killer cells in the epithelium of the gut distinguishes two different coeliac diseases.

In a longterm study, we have divided coeliac disease into two distinct entities (abortive and permanent) based on the occurrence of large granular lymphocytes and natural killer cells within the epithelium of the gut. The natural killer and large granular lymphocytes cells were characterised by either immunohistochemical or phase contrast microscopical procedures on the initial biopsies from 15 children with coeliac disease. They were compared with seven individuals with partial villus atrophy and eight with normal villous morphology. Although the histological findings were similar in the initial biopsies of all patients with coeliac disease, the patients with permanent coeliac disease had a significantly lower number (0.41(0.61)cells/mm2) of large granular lymphocytes and natural killer cells compared with those patients with abortive coeliac disease (11.93 (6.23) cells/mm2). Those in the permanent group developed a significantly more pronounced flat mucosa after gluten challenge or provocation compared with the abortive group and had to remain on a strict gluten free diet in contrast with those in the abortive group. Thus, the occurrence of intraepithelial large granular lymphocytes and natural killer cells characterises two distinctly different coeliac diseases. Based on our results neither the histological evaluation of the biopsy nor the utilisation of the revised European Society for Paediatric Gastroenterology and Nutrition (ESPGAN) Criteria are adequate in diagnosing the two types of coeliac disease.

Celiac Disease

The effect of needle biopsy procedure on prepubertal rat testis.

Testicular needle biopsies were performed in 20 prepubertal rats. Ten rats were used as a control group. Spermatohistogenesis was observed in the tubuli (mean number: 17) of each biopsy. The biopsy procedure caused tubular damage which extended to 0.2-4% of the entire testicular volume. Twenty percent of the rats had severe unilateral testicular atrophy at the site of the procedure. A significant compensatory tubular hypertrophy occurred in the contralateral testis that was observed 50 days after the procedure. Eighty percent of the rats produced the normal number of offspring, independent of the occurrence of unilateral testicular atrophy. The histology of the contralateral testis was normal in all animals; thus, no adverse effect from the biopsied testis occurred.

Animals

Antigliadin and antiendomysium antibody determination for coeliac disease.

The value of IgG and IgA gliadin antibodies (AGA) was compared with that of IgA endomysium antibodies (EMA) for the diagnosis of coeliac disease. Three hundred and six of 340 (90%) children with untreated coeliac disease (flat mucosa) had EMA and 338/340 (99.4%) had IgG AGA and/or IgA AGA. Only 1/340 (a 7 year old boy with selective IgA deficiency) had neither AGA nor EMA. Absence of EMA is more frequent in coeliac patients younger than 2 years than in older patients (32/277 compared with 1/62). EMA were present in 4/211 (2%) of comparison subjects (normal mucosa), IgA AGA in 12/211 (6%), and IgG AGA in 74/211 (35%). The specificity of AGA cannot be calculated from these figures as they are biased. The combined determination of AGA and EMA, taking advantage of the high sensitivity of AGA and the high specificity of EMA, gives an excellent prediction of the condition of the mucosa: 247/248 patients (99.6%) with positive EMA and positive IgG AGA and IgA AGA had a flat mucosa, whereas 136/137 patients (99.3%) with neither AGA nor EMA had a normal mucosa. During a gluten free diet EMA and AGA disappear. Their presence or absence is therefore an indicator of dietary compliance. After reintroduction of gluten into the diet 110/134 (82%) of the patients who had a flat mucosa at diagnosis relapsed, but 24/134 still had a normal mucosa after 2-15 years of challenge. All these patients without a morphological relapse were less than 2 years old at diagnosis so we conclude that patients who are young at diagnosis should be challenged. AGA often reappear earlier than EMA. After one month of challenge 93% of patients are AGA and 69% EMA positive. After more than three years of gluten intake the percentage of AGA positive patients decreased to about 50% whereas the percentage of EMA positive sera was then highest (93%). Therefore EMA are more sensitive for the detection of 'silent' relapse after prolonged periods of gluten intake.

Adolescent

Does hydrocele affect later fertility?

The purpose of this study was to investigate the prognosis for fertility in children with hydrocele. Our results show that hydrocele seems to be more of a symptom than an actual pathological entity. It occurs both with an open and a closed processus vaginalis. Bilateral hydrocele seems to be a rare occurrence, mostly affecting infants or children under 1 year of age. Hydrocele on its own seems to have no direct effect on later fertility. In the presence of certain associated pathological findings, however, the testes are significantly altered. Children with hydrocele and pathological findings are significantly older than hydrocele patients with no associated pathology. As a practical recommendation, hydrocele does not require immediate surgery. In the presence of hydrocele and certain associated pathology, however, surgery makes good sense.

Cryptorchidism

Postnatal testicular maldevelopment in unilateral cryptorchidism.

Histomorphometric analysis of semi-thin sections was performed on testicular biopsies of 232 unilaterally cryptorchid testes and 195 of their contralateral descended partners. The results demonstrated a decreased number of germ cells detectable from the first year of life. There was delayed and defective transformation of gonocytes to Ad spermatogonia, which normally is complete at age 6 months, delayed or failed transformation of Ad spermatogonia to primary spermatocytes, which normally commences at age 3 years and decreased numbers of Leydig cells. These abnormalities were present in the unilaterally cryptorchid testes and their contralateral descended partners but they were more severe, of earlier onset and more progressive in the cryptorchid testes. These findings are compatible with the hypothesis that hypogonadotropic hypogonadism is the cause of the increased incidence of infertility seen in unilateral cryptorchidism.

Biopsy

Testicular and vascular changes in children and adults with varicocele.

We analyzed bilateral testicular biopsies of 188 infertile patients with idiopathic left varicocele. The left side had significant pathological tubular testicular changes compared to the right side, whereas in only 7 per cent of the patients tubular damage was more pronounced on the right side. The Leydig cell pathological score was identical in both testes in 95 per cent of the patients. However, the lower the Leydig cell pathological score the better the testicular histology, suggesting an association between Leydig cell score and testicular function. Of the 188 patients 11 boys and 8 adults were randomly selected, and they displayed clear endothelial proliferative lesions of the capillaries at the ultrastructural level. Proliferative endothelial lesions in the patients with varicocele preceded the testicular changes. This, together with the prevalence of tubular damage at the site of the varicocele and the reversibility of these changes postoperatively, emphasizes the deleterious effects of varicocele as a cause of infertility in these patients. Early surgery for boys in whom the first signs of testicular atrophy occur is highly recommended.

Adolescent

Pulsatile LHRH therapy in patients with oligozoospermia and disturbed LH pulsatility.

Pulsatile administration of LHRH can drive the pituitary to secrete LH and FSH in a pattern that closely mimics the physiological pattern of the hypothalamic-pituitary-gonadal axis. As there is evidence that infertility in some men is due to dysfunction of this axis, 14 men with reported infertility of more than 2 years duration were treated by long-term pulsatile LHRH therapy. They were 24-42 years of age, with variable degrees of oligozoospermia, elevated FSH levels but normal LH and testosterone levels. The number of endogenous LH pulses/24 h was less than eight in all 14 subjects. The degree of testicular damage was assessed semi-thin sections prepared from biopsies of both testes. Scores for spermatogonia per seminiferous tubule (SPT) were calculated from the actual number of Ad-spermatogonia/tubule. Patients were grouped according to sperm density and SPT score (groups I-III). Pulsatile LHRH therapy was administered by means of a portable infusion pump; 4 micrograms LHRH were administered subcutaneously every 120 min for a period of 6 months. This treatment restored the normal pattern of LH secretion to 12 LH pulses/24 h in all patients. A statistically significant decrease of mean FSH levels to normal, and an increase of mean LH levels was observed in most of the 14 patients. Testosterone values did not change in any group. Marked improvement of the sperm count was observed in eight out of 14 patients (groups I and II) and three pregnancies were reported during the treatment periods. These results suggest that some states of male infertility are due to hormonal dysregulation and that these patients may benefit from pulsatile LHRH therapy.

Adult

Long-term treatment of central precocious puberty with an intranasal LHRH analogue: control of pituitary function by urinary gonadotropins.

Daily subcutaneous doses of luteinizing hormone-releasing hormone (LHRH) analogues are a well-established therapy for gonadotropin-dependent precocious puberty. Reports on intranasally administered analogues, however, are controversial. We studied the effect of intranasal D-Ser(TBU)6-LHRH(BUS) on growth rate, skeletal maturation, and urinary gonadotropins in five girls and one boy with central precocious puberty (CPP) who had been treated for 1.4-2.3 years (mean 1.9). Because of the potential antifertility effects of LHRH analogues, testicular histology was analysed in the boy. In the five children with accelerated growth, the bone age-related velocity of height gain decreased from 10.58 +/- 2.77 to 5.82 +/- 1.8 cm/year (means +/- SD, P less than 0.01), and the ratio of change in bone age to change in chronological age fell below 1. Basal luteinizing hormone (LH), and LHRH-stimulated LH and follicle stimulating-hormone, at pubertal levels before treatment, decreased significantly in all children, normalizing in four (P less than 0.04). During therapy, pituitary function was best controlled by urinary LH, which correlated with clinical data. After 13 months of therapy, testicular histology showed degenerated Sertoli cells, and absence of B- and Ap-spermatogonia and of primary spermatocytes in the boy. We conclude that: (1) Efficient long-term suppression of central precocious puberty--including accelerated growth and skeletal maturation--can be maintained by intranasal dosage of BUS. (2) Urinary LH reflects pituitary function and proves to be a reliable guide to adjustment of the LHRH-analogue dose regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal

Development of cryptorchid testes.

Development of normal germ cells during childhood is a continuous process which ends at puberty. Cryptorchid gonads have severe impairment of their germ cell development which is more pronounced the higher the gonads are situated. However, all newborns with intra-abdominal testes had a normal number of germ cells. This strongly supports the theory that cryptorchidism is a disease and not a malformation. As a consequence, adequate and early treatment of cryptorchid boys should be undertaken in order to preserve good chances of fertility.

Biopsy

Relevance of urinary gonadotrophins.

The assay of urinary LH and FSH in first morning void urine can be used for the differential diagnosis between anorchism and bilateral cryptorchidism with impalpable testes. Furthermore, levels of urinary LH and FSH excretion and their response to intranasal stimulation with LH-RH prove helpful in the follow-up of patients under hormonal treatment, i.e. prolonged stimulation in hypogonadotrophic hypogonadism or suppression by an LH-RH analogue, for instance in precocious puberty. By increasing the sensitivity of the assay, the value of urinary gonadotrophins for the differential diagnosis and survey of hormonal treatment in very young children can be examined, and investigations of this kind are currently taking place. The method used obviously cannot assess the bioactivity of the excreted hormone, nor can it depict the pulsatility of gonadotrophin secretion.

Cryptorchidism