Brain anatomical substrates of mirror movements in Kallmann syndrome.

Among male patients affected by Kallmann syndrome, a genetically determined disease due to defective neural migration leading to hypogonadropic hypogonadism and hypo/anosmia, about 40% present the peculiar phenomenon of mirror movements, i.e. involuntary movements mirroring contralateral voluntary hand movements. Several pathogenic hypotheses have been proposed, but the ultimate neurological mechanisms are still elusive. The aim of the present study was to investigate brain anatomical substrates of mirror movements in Kallmann syndrome by means of a panel of quantitative MRI analyses. Forty-nine male Kallmann syndrome patients underwent brain MRI. The study protocol included 3D-T1-weighted gradient echo, fluid attenuated inversion recovery and diffusion tensor imaging. Voxel-based morphometry, sulcation, curvature and cortical thickness analyses and tract based spatial statistics were performed using SPM8, Freesurfer and FSL. All patients underwent a complete physical and neurological examination including the evaluation of mirror movements (according to the Woods and Teuber criteria). Kallmann syndrome patients presenting with mirror movements (16/49, 32%) displayed the following brain changes: 1) increased gray matter density in the depth of the left precentral sulcus behind the middle frontal gyrus; 2) decreased cortical thickness in the precentral gyrus bilaterally, in the depth of right precentral sulcus and in the posterior portion of the right superior frontal gyrus; and 3) decreased fractional anisotropy in the left hemisphere involving the temporal lobe and peritrigonal white matter. No differences were shown by cortical curvature and sulcation analyses. The composite array of brain changes observed in Kallmann syndrome patients with mirror movements likely represents the anatomical-structural underpinnings leading to the peculiar derangement of the complex circuitry committed to unilateral hand voluntary movements.

Effect of a single injection of testosterone enanthate on 17ß estradiol and bone turnover markers in hypogonadal male patients.

PURPOSE: Several clinical studies testify the critical role played by estrogens in male bone metabolism. The aim of our study is to assess the effect of a single injection of testosterone enanthate in a group of hypogonadal men on 17ß estradiol serum levels and some bone metabolic parameters. METHOD: Twenty-one hypogonadal males were given one testosterone enanthate injection (250 mg). Blood samples were drawn before the injection and after 1, 2 and 3 weeks. The following variables were measured: Total testosterone (TT), 17ß estradiol (17ß E2), Sex hormone binding globulin, total alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen (CTx). RESULTS: After testosterone injection, both TT and 17ß E2 increased, peaking 1 week after the injection. Individual observation of the response of 17ß E2 to testosterone showed that a subgroup (n = 9) failed to respond with any increase in 17ß E2 at any of the weekly tests (group E2-), while the remainder (n = 12) showed a significant increase in 17ß E2, which reached a mean value three times higher than at baseline (group E2+). The E2- patients reached a TT peak lower than that observed in the E+ group. CTx serum levels declined progressively in the E2+ group, reaching the significance (p = 0.03) at the end of the study, while it did not change in E- group. CONCLUSION: This study suggests that a single injection of testosterone might have different effects on the production of endogenous estrogens, and a significant reduction of bone resorption parameters takes place only in the patients who show a significant increase of 17ß estradiol in response to testosterone administration.

Brain changes in Kallmann syndrome.

BACKGROUND AND PURPOSE: Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome-related brain changes with conventional and novel quantitative MR imaging analyses. MATERIALS AND METHODS: Forty-five male patients with Kallmann syndrome (mean age, 30.7 years; range, 9-55 years) and 23 age-matched male controls underwent brain MR imaging. The MR imaging study protocol included 3D-T1, FLAIR, and diffusion tensor imaging (32 noncollinear gradient-encoding directions; b-value=800 s/mm2). Voxel-based morphometry, sulcation, curvature, and cortical thickness analyses and tract-based spatial statistics were performed by using Statistical Parametric Mapping 8, FreeSurfer, and the fMRI of the Brain Software Library. RESULTS: Corpus callosum partial agenesis, multiple sclerosis-like white matter abnormalities, and acoustic schwannoma were found in 1 patient each. The total amount of gray and white matter volume and tract-based spatial statistics measures (fractional anisotropy and mean, radial, and axial diffusivity) did not differ between patients with Kallmann syndrome and controls. By specific analyses, patients with Kallmann syndrome presented with symmetric clusters of gray matter volume increase and decrease and white matter volume decrease close to the olfactory sulci; reduced sulcal depth of the olfactory sulci and deeper medial orbital-frontal sulci; lesser curvature of the olfactory sulcus and sharper curvature close to the medial orbital-frontal sulcus; and increased cortical thickness within the olfactory sulcus. CONCLUSIONS: This large MR imaging study on male patients with Kallmann syndrome featured significant morphologic and structural brain changes, likely driven by olfactory bulb hypo-/aplasia, selectively involving the basal forebrain cortex.

Gonadal function in males with autoimmune Addison's disease and autoantibodies to steroidogenic enzymes.

Steroidogenic enzyme autoantibodies (SEAbs) are frequently present and are markers of autoimmune premature ovarian failure (POF) in females with autoimmune Addison's disease (AAD). The prevalence and significance of SEAbs in males with AAD have not yet been defined. We studied the prevalence of SEAbs in a large cohort of males with AAD and assessed the relationship between SEAbs positivity and testicular function. A total of 154 males with AAD (mean age 34 years) were studied. SEAbs included autoantibodies to steroid-producing cells (StCA), detected by immunofluorescence, and steroid 17α-hydroxylase (17α-OHAbs) and side chain cleavage enzyme (SCCAbs) measured by immunoprecipitation assays. Gonadal function was evaluated by measuring follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), sex hormone-binding globulin (SHGB), anti-müllerian hormone (AMH) and inhibin-B (I-B). Twenty-six males, 10 SEAbs((+)) and 16 SEAbs((-)), were followed-up for a mean period of 7·6 years to assess the behaviour of SEAbs and testicular function. SEAbs were found in 24·7% of males with AAD, with the highest frequency in patients with autoimmune polyendocrine syndrome type 1 (APS-1). The levels of reproductive hormones in 30 SEAbs((+)) males were in the normal range according to age and were not significantly different compared to 55 SEAbs((-)) males (P > 0·05). During follow-up, both SEAbs((+)) and SEAbs((-)) patients maintained normal testicular function. SEAbs were found with high frequency in males with AAD; however, they were not associated with testicular failure. This study suggests that the diagnostic value of SEAbs in males with AAD differs compared to females, and this may be related to the immunoprivileged status of the testis.

Immediate- and late-hemodynamic coronary effects of tadalafil in men with erectile dysfunction and coronary artery disease.

We investigated whether coronary flow reserve (CFR) can be modified by tadalafil, a long-acting phosphodiesterase 5 (PDE5) inhibitor, in patients with documented coronary artery disease (CAD). CFR was non-invasively evaluated in 12 men with a positive history for erectile dysfunction (ED) and angiographically documented CAD, in the distal portion of the left anterior descending coronary artery, free from critical stenosis, with contrast enhanced echocardiography at time zero (T0). Then, after 20 mg tadalafil was orally administered CFR measurement was repeated after 2 h (T1) and after 24 h (T2). Doppler curves suitable for the analysis were obtained in all patients (CFR feasibility: 100%). The peak diastolic velocity after adenosine infusion increased from 71.3+/-14.3 cm/s at T0 to 82.5+/-24.0 at T1 (P=NS) and to 89.5+/-21.1 at T2 (P=0.0010). CFR after tadalafil increased significantly from 2.6+/-0.3 at T0 to 3.1+/-0.7 at T1 (P=0.0078) and a further increment was found at T2 (3.5+/-0.9; P=0.0010 vs T0). Our study shows that oral administration of tadalafil exerts a long standing, potentially beneficial effect on coronary microvasculature in patients with ED.

Licorice consumption and serum testosterone in healthy man.

We have previously found that licorice can reduce serum testosterone in healthy men. These results were not confirmed in another study, where the same amounts of licorice did not decrease salivary testosterone values. In the actual study we treated more cases with the same amount of licorice and reproduced our previous data. The mean testosterone values decreased by 26 % after one week of treatment (p < 0.01). There was also a significant increase in 17-OHP and LH concentrations and a slight, but not significant decrease in free testosterone. Licorice treatment, in addition, did not affect the response of testosterone and 17-OHP to stimulation with beta-HCG.

[Evaluation of the adherence to the asthma guidelines by the administration of a questionnaire in community pharmacies]. / Valutazione dell'adesione alle linee guida per il trattamento farmacologico del paziente asmatico attraverso la somministrazione di un questionario in farmacia.

BACKGROUND: Several studies demonstrate that the adherence to asthma guidelines (GL) is poor, but only a few of them were performed in community pharmacies. Thus, we decided to study this phenomenon by administering a questionnaire (Q) in two pharmacies. METHODS: A Q was developed and administered to 138 patients-customers of two community pharmacies in Rome. RESULTS: The severity of the disease was established based on the frequency of daytime and nocturnal symptoms before therapy, following the stepwise approach recommended by the current GL. We observed up to 90 different treatments, while those listed by the GL, long-term preventive or quick-relief for the four categories of asthma, are only 19. In particular, many of them included antihistaminic drugs and mucoactive agents, pharmacological classes not recommended by the GL, while certain long-term preventive therapeutic schemes did not include glucocorticoids. CONCLUSIONS: The analysis of the effects on daytime and nocturnal symptoms and the interferences of the disease with school and work, showed that the control of asthma was inadequate, probably due to the low adherence to the GL. In conclusion, this small pilot study, which does have several methodological limitations (small population and geographic area, small number of pharmacies involved, the use of a Q to obtain information not easily reported by the patient) confirms the important role played by pharmacists in the analysis of the adherence of pharmacological treatments to official GL.

Unilateral adrenal tumor, erectile dysfunction and infertility in a patient with 21-hydroxylase deficiency: effects of glucocorticoid treatment and surgery.

In untreated congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHDS) the presence of adrenal and testicular tumors had been described; however little is known about the effect of the enzymatic defect on fertility in males. We studied a male adult patient affected by 21OHDS for infertility, after a long period of discontinuation of glucocorticoid therapy and then during resumption of treatment and 8 months after monoadrenalectomy. The initial spermatic count revealed azoospermia and testicular needle aspiration showed a cytological picture consistent with prepuberty. The morphofunctional study revealed a right adrenal mass with reduced uptake at radioscan. Treatment was resumed with onset of impotency, which improved after reduction of the dose of glucocorticoids. The patient was monoadrenalectomised and his spermatic count increased. The patient shows that corticosteroid therapy in 21OHDS should be continued lifelong to avoid adrenal hyperplasia with possible areas of autonomy and to allow regular fertility. Impotence during treatment is probably due to a decrease of excessive adrenal androgens while testicular androgen production is still suppressed.

[Results of laparoscopic bilateral varicocelectomy]. / Risultati della varicocelectomia bilaterale laparoscopica.

Left varicocele (LV) is a common clinical condition that is present in approximately 15% of the general male population. Bilateral varicocele (BV) is an association of clinical LV and subclinical or ultrasound diagnosed right varicocele. Recent diagnostic technology suggests that BV is much more common than previously suspected varying from 15 to 57%. The laparoscopic technique offers the possibility of planning bilateral varix ligation but only a few reports are currently available. The aim of this study was to evaluate the outcome of contemporary bilateral correction of BV on spermatogenesis. From 1992 January to 1998 December a total of 207 patients with clinical left varicocele and a pathological sperm count were studied. Scrotal sonography was performed and in 96 patients (group A) subclinical right varicocele was diagnosed while 111 patients (group B) only had LV. 84 patients were married and had tried unsuccesfully for a pregnancy for at least one year before evaluation. All patients underwent laparoscopic varicocelectomy, performed under general anesthesia with a three trocar technique with application of clips to the spermatic vein and resection. Patients with right reflux received bilateral varix ligation. Operating time averaged 28 minutes for unilateral cases and 42 minutes for bilateral legatures. No significant differences were found in age distribution or preoperative seminal paramenters between the two groups. Postoperative hospital stay was 1.2 and 1.3 days respectively. 168 patients underwent sperm count four to six months after surgery. Both groups showed improvements in number (group A 41 millions, group b 27 millions), 2nd hour motility (group A 32%, group B 19%) and morphology (group A 52%, group B 51%). 95 patients achieved normalization of seminal parameters, 40 (63%) in group A and 37 (30%) in group B, and there was a statistically significant difference between the two groups. The pregnancy rate was calculated on married population after one year; it was 41% in total. The role of the subclinical right varicocele associated to clinical left varicocele is uncertain and there are few papers concerning this argument. In this serie normalization of seminal parameters and the pregnancy rate were significantly higher in patients with bilateral correction of reflux. In conclusion our data confirm that subclinical right reflux also has a detrimental effect on spermatogenesis and we suggest that it must be corrected contemporary when associated with clinical left varicocele.

[Transformation of Waldenström disease into chronic myeloid leukemia]. / Trasformazione di malattia di Waldenström in leucemia mieloide cronica.

The authors describe a case of a 83 years old patient affected with Waldenström disease whose shift in chronic myelogenous leukaemia is surprising because the quickness of the fact and, even more, because the following very fast appearance of quickly fatal paravertebral granulocytic sarcoma, as extramedullary blast crisis expression. This feature appears unusual in old subject.

Interaction of hyaluronic acid with mucin, evaluated by gel permeation chromatography.

Hyaluronic acid (HA) is known to increase the ocular bioavailability of ophthalmic drugs not only for its viscous properties but also for its specific affinity for ocular mucins. This phenomenon, called bio- or mucoadhesion, can be evaluated in vitro by mechanical tests which, however, require considerable amounts of mucin (M) that are difficult to obtain from ocular surfaces. Thus, we developed an alternative method, based on gel permeation liquid chromatography, to examine the interaction of HA with microgram quantities of mucin. HA (from human umbilical cord or rooster comb) were fractionated using a Sepharose CL-4B column, before and after incubation with porcine gastric mucin (PGM), and the fractions were analyzed by a specific assay based on the histological dye Stains-all. PGM interacted with high molecular weight (M.W). HA, causing the displacement of low M.W., non-covalently bound, HA fragments, which were eluted under a distinct chromatographic peak. By quantitating the relative area of this peak, an evaluation of the mucoadhesion of HA could be obtained. This method could be useful to study the interaction between HA and microgram quantities of ocular M (mucin), obtained from individual patients or normal subjects.

DNA flow cytometry of left and right testes in normospermic patients affected by left varicocele.

To assess whether changes in spermatogenesis are present in men suffering from varicocele who are still normospermic, a comparative flow cytometric analysis of the left and right testicular DNA content was performed on 26 young normospermic males (sperm density > 20 x 10(6)/ml), with varying degrees of asthenospermia. Cell samples were obtained by fine needle aspiration biopsy. Flow cytometric analysis revealed four peaks in the nuclear DNA content: (i) two peaks for haploid cells (1-A), the first composed of highly condensed nuclear cells (1Ac), essentially spermatozoa, and the second of less condensed cells, essentially spermatids (1-Anc): (ii) a third peak of diploid cells (2-D): somatic cells, G1-stage spermatogonia, primary and secondary spermatocytes and (iii) a fourth peak of tetraploid cells, essentially postleptotene primary spermatocytes and G2-M-stage spermatogonia (4-T). Flow cytometry showed the left testis to have a lower percentage of haploid cells than the right (mean 48.4 +/- 17.9 versus 57 +/- 15.4%, P < 0.05). Significantly fewer condensed cells were found on the left side than on the right (respectively 19.7 +/- 11.2 versus 31.5 +/- 13.5%, P < 0.004). The diploid cell percentage was significantly higher in the left testis than in the right (37.0 +/- 18.5 versus 25.5 +/- 9.6, P < 0.003). No statistically significant differences were found in respect of percentages of either non-condensed and tetraploid cells (respectively 26.6 +/- 14.8 and 11.3 +/- 5.6 on the left and 25.9 +/- 10.3 and 12.4 +/- 6.2 on the right). Flow cytometric analysis of cadaver biopsy tissue showed no statistically significant difference between left and right testicles in respect of the percentages of haploid, diploid and tetraploid cells. The reduced percentage of haploid cells and the increase in diploid cells observed in the left testis of our subjects indicate that the testicular function is impaired to a greater extent in the testis ipsilateral to varicocele than in the contralateral testicle.

Clinical and hormonal aspects of male hypogonadism in myotonic dystrophy.

In order to study male hypergonadotropic hypogonadism as completely as possible, and to evaluate its possible effects on muscle atrophy and sexuality, RIA or IRMA methods were used to measure the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, total (T) and free (FT) testosterone, estradiol (E), dihydrotestosterone (DHT), sex hormone binding globulin (SHBG), androstenedione (A) and 17-OH-progesterone (17-OH-P) in 29 patients with myotonic dystrophy (MD). The mean hormonal levels +/-SD were: LH 8.0 +/- 4.4 mIU/ml, FSH 17.4 +/- 11.5 mIU/ml, A 200 +/- 130 ng/dl (all higher than in controls); T 406 +/- 290 ng/dl, FT 22.7 +/- 7.0 pg/ml, DHT 55.5 +/- 29.7 ng/ml (all lower than in controls). The low FT and DHT levels (never previously studied in MD) confirm the androgenic deficiency. The high androstenedione levels and low testosterone concentrations suggest defective enzyme 17-dehydrogenase. The duration of the disease correlated with both testosterone (r = -0.56) and FT levels (r = -0.59), showing that hypogonadism tends to worsen progressively. When the patients were divided into three groups on the basis of the severity of muscle involvement (A, B and C), LH and FSH levels were higher in group C (more severe disease) than in group A, respectively 9.3 +/- 4.7 and 20.6 +/- 12.3 mIU/ml versus 4.8 +/- 0.9 and 8.4 +/- 3.8, p < 0.03; T levels were lower in group C than in group A, 337.3 +/- 263.4 ng/dl versus 649.7 +/- 320.3 (p < 0.03); however, there was no significant difference in the FT levels of the three groups, which may imply that hypogonadism is unlikely to have a direct effect on muscle atrophy. About 25% of our patients were impotent; these subjects had higher LH and FSH (p < 0.001) and lower FT levels than the patients who were not impotent (p < 0.03). However, hypogonadism may not be the only cause of impotence as all of the impotent patients belonged to group C and had a very high (CTG)n triplet expansion. We hypothesise that hypogonadism and sexual impairment could be partially due to a muscle cell alteration: i.e. a dysfunction of both the testicular peritubular myoid cells and of the corpus cavernosum smooth muscle.

Bone mass and mineral metabolism in Klinefelter's syndrome.

A reduced bone mineral density (BMD) is frequently observed in hypogonadal males; however, very little is known on bone and mineral metabolism in Klinefelter's syndrome (KS). In this study 32 XXY KS patients and 24 healthy age-matched male controls were examined. Serum total and free testosterone (TT and FT) were significantly lower in patients than in controls (TT in KS, 15.1 +/- 7.8 nmol/l; controls, 30.4 +/- 9.1; p < 0.001. FT in KS, 81.8 +/- 24.9 pmol/l; controls, 135.7 +/- 16.4; p < 0.001). 17 beta-Estradiol was slightly higher in KS patients (KS, 49.0 +/- 27.1 pg/ml; controls, 39.3 +/- 16.4 pg/ml), but the difference was not significant. BMD, measured at the spine (L2-4) and at the proximal epiphysis of the left femur, was similar in patients and in the control group (spine: KS, 1.016 +/- 0.142; controls, 1.085 +/- 0.144 g/cm2; p = not significant. Femoral neck: KS, 0.926 +/- 0.149; controls, 0.926 +/- 0.122 g/cm2; p = not significant). Bone GLA protein (BGP) was significantly higher in the KS group (12.7 +/- 4.8 vs 8.9 +/- 5.2 ng/ml; p < 0.02), while serum calcium, serum phosphate, calciotrophic hormones and the fasting urinary hydroxyproline/creatinine ratio (OHP/Creat) were similar in the two groups. A positive relationship between FT and both spine and femoral BMD was found in KS patients. Furthermore, OHP/Creat ratio was inversely related to BMD at the femur, and positively related to BGP in KS patients, but not in normal subjects. These findings suggest that (1) KS patients have normal bone mass, most probably because the hypogonadism is moderate; and (2) patients with lower bone mass appear to have higher bone turnover.

Male hypogonadism in myotonic dystrophy is related to (CTG)n triplet mutation.

The Authors considered the relationship between hypogonadism in myotonic dystrophy (MD) and MT-PK gene mutation. Twenty-seven subjects were studied, and the (CTG)n amplification varied from 70 to 1520 (mean 661 +/- 463). Hypergonadotropic-hypogonadism with LH levels of 6.94 +/- 3.87 and FSH 14.54 +/- 9.58 IU/L was present; testosterone still showed normal values (505.7 +/- 376.2 ng/dl), but 44.4% of patients had abnormal serum level less than 250 ng/dl. We found a significant correlation (p < 0.001) between CTG repeat size and levels of both LH and FSH: these findings suggest that the severity of hypogonadism is related to MT-PK gene mutation.

Concomitant ceco-appendicular and urinary tuberculosis. Description of two rare cases: physiopathological and diagnostic remarks.

Two cases of specific tubercular processes in the ceco-appendicular zone and the urinary system in men aged 25 and 30 years are described. Both patients reported abdominal pain and persistent fever that did not respond to treatment. Surgery revealed ulcerated appendix, intraperitoneal serous exudate, ascitic liquid, peritoneal ulcerocaseous nodules, and fibrous adhesions. Histological sections revealed a tubercular puchet in the ceco-appendicular zone. Subsequent x-ray test in response to reports of frequent painful urination showed specific lesions in the papillae and renal ureteral ampullae, and urine cultures were positive for Koch's bacillus. Treatment with streptomycin, followed by isoniazid, rifampicin, ethambutol, and morinamid for 2 years, was effective.

High intensity physical exercise induced effects on plasma levels of copper and zinc.

Physical exercise leads to many metabolic, cardiovascular, and muscular changes in the body. The trace elements (TE) zinc and copper are directly involved, as enzymatic cofactors, in many of these processes, especially those related to nutrients metabolism, oxygen transport, and formation of usable energy. The effects of high-intensity physical exercise on plasma levels of CU2+ and Zn2+ in 19 subjects are investigated (9 males and 10 females). Plasma copper concentration decreases, and plasma zinc concentration increases, after exercise, in both sexes. After 30 min recovery, both TE concentration values shifts toward rest values in both sexes. These results only partially agree with literature data, probably because we used the treadmill exercise, which makes many muscles work, whereas other authors made their subjects perform a cycloergometer exercise. Physical exercise causes a marked redistribution of TE (copper and zinc) between body stores, bloodstream, and tissues. The condition of high metabolism may lead to a deficiency of TE, requiring supplementation in order to maintain high level performance.

As regards to the immunosuppressive treatment in kidney transplant. Possibilities and limits.

The Authors deal with the immunosuppressive drugs administered to kidney-transplant receiving. The point out the complexity of the utilized pharmacological schemes, underlining the metabolic and immunologic iatrogenic effects brought about by this therapeutic iter, which should not neglect the clinical conditions of the patient.

Achievement of spermatogenesis and genital tract maturation in hypogonadotropic hypogonadic subjects during long term treatment with gonadotropins or LHRH.

15 subjects with Hypogonadotropic Hypogonadism (HH) were treated with either gonadotropins (13 cases) or pulsatile subcutaneous Luteinizing Hormone Releasing Hormone (LHRH) (2 cases) for up to 42 months, to study the effects of therapy step by step. The following results were obtained: (A) In postpubertal HH (5 cases = Group A), therapy brought about onset of spermatogenesis within 3 months and its normalization within 6 months. In HH of prepubertal onset (10 cases = Group B), spermatogenesis started within 9 to 21 months and became normal in only 3 cases after at least 18 months. The best sperm counts were obtained in Group A in the third month of treatment (41.75 +/- 43.68 mil./ml) and in Group B in the 36th month (14.87 +/- 17.06 mil./ml). Sperm motility was normal in the majority of the cases in Group A from the beginning but did not become normal in Group B. (B) Seminal fructose and zinc were normal from the beginning of therapy in 66% of the cases in both groups. Zinc became normal in 100% within 3 months in Group A, in Group B within 18. Carnitine was normal in 50% of cases in both groups, contemporaneous with sperm appearance. Transferrin was normal in Group A after appearance of spermatozoa, but in Group B never became normal. (C) We hypothesize that the recovery of fertility passes through the following stages: (1) Functional recovery of Leydig cells, followed by seminal vesicles and prostate. (2) Recovery of epididymal function, which probably implies beginning of the tubular function. Recovery of Sertoli cell function occurs with more difficulty.