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.

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.

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.

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.

A case of subprimary suprarenal tuberculosis.

In spite of the current availability of new and more up-to-date methods of prevention, diagnosis and therapy, specific forms in general and the ability to perform rapid, efficacious and resolutory operations, a number of cases of subprimary or secondary tuberculosis still exist which are most probably the result of delayed diagnosis, contagious episodes or the failure to adhere to recommended treatment protocols and, often, less than optimum medical therapy. A rare case of adrenal tuberculosis diagnosed in a patient hospitalized for left renal calculosis is reported. Routine tests indicated a specific form of diagnosis, and during surgery for left renal calculosis the patient underwent left adrenalectomy. Histological tests confirmed the initial diagnosis. For 180 days after the operation the patient received pharmacological treatment directed specifically against Koch's bacillus.

[Treatment of male hypogonadotropic hypogonadism]. / La terapia dell'ipogonadismo ipogonadotropo maschile.

Males affected by hypogonadotropic hypogonadism can be treated with androgen replacement therapy, if they do not wish fertility. In order to limit or avoid androgen toxicity on the liver, it is possible to use testosterone undecanoate (which is absorbed in the gut by lymphatic system) at the dose of 160-240 mg/die or testosterone esters administered intramuscolarly at the dose of 250 mg/month. Estradiol and DHT derived from testosterone catabolism can be in excess therefore they can be provoke toxic phenomena, even if slight, such as gynecomastia or prostatic diseases. If patients wish fertility, they must be treated with gonadotropins or pulsatile LHRH. Therapeutic effects are very different depending on the different origin of the hypogonadism. In postpubertal onset hypogonadotropic hypogonadism, the response is constant and rapid; sperm count normalization can be reached within 6 months with the only hCG. Prepubertal onset hypogonadotropic hypogonadal men need hu-FSH too and longer treatment (18-24 months); sperm count normalization can be reached in less than half case. Nevertheless fertility can be reached even in oligozoospermic stage. Negative prognostic factors are: pan-hypopituitarism, cryptorchidism, how old are the patients at the beginning of the treatment and small testis volume. It is not yet clear if pulsatile LHRH therapy is profitable in terms of therapeutic results.

[Physiopathological and nutritional changes in hemodialysis patients and in those who have undergone renal transplantation]. / Le alterazioni fisiopatologiche e nutrizionali nei soggetti emodializzati ed in quelli sottoposti a trapianto renale.

The paper examines the complex metabolic behaviour of patients undergoing hemodialysis and renal transplantation. It underlines the importance of the metabolic and nutritional status of these patients since inadequate nutritional therapy may result in the failure of hemodialysis and/or surgery. Given the complexity of the metabolic syndrome and its bronchopulmonary, cardiovascular and septic complications, it is necessary to monitor the various chemical and clinical parameters in these patients in order to guarantee an optimal recovery and satisfactory survival rate. Fortunately today, by replacing the use of Azathioprine, Cyclosporin--irrespective of its collateral and/or secondary effects--has replaced the use of corticosteroids whose immunodepressive action made it obligatory to start simultaneous prophylactic antibiotic treatment and/or chemotherapy in order to avoid the development of other chance disease. The paper also reports the findings of a retrospective study (1976-1986) which evaluated various physiopathological and metabolic parameters and compared them to data reported in the literature.

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.

[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.

[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.

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.

[The role of emotional stress in pathogenesis of gastrointestinal diseases and the importance of psychopharmacologic combinations in their treatment]. / Ruolo dello stress emotivo nella patogenesi di alcune affezioni gastrointestinali ed importanza dell'associazione psicofarmacologica nel loro trattamento.

In view of the importance of the emotional stress in some gastrointestinal diseases pathogenesis among which anxiety and/or depression appear to play an appreciable role, the Authors have analysed a number of sensitive colon and duodenal ulcers whose psychopharmacologic treatment has resulted crucial in the resolution of these diseases.

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.

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.

Stuttering and tics in twins.

A total of 63 twin pairs (22 MZ and 41 DZ), with one or both members affected by not organic stuttering and/or tics, have been drawn out of the Mendel Institute's twin file. Concordance of stuttering was observed in 10:12 MZ, but only in 2:19 DZ twin pairs; concordance of tics in 6:10 MZ and in 2:22 DZ twin pairs. Stuttering did not come out significantly associated either with other disturbances of language or with an IQ under the average; almost always it was possible to find out a precipitating factor. Significant relations between stuttering and tics could not be stated. Sex ratio, obtained regarding any affected subject separately, clearly turned in favour of males both in stuttering (32:12) and in tics (27:12). Stutterers and left-handers incidence in the families of stuttering subjects appeared significant in comparison with families of subjects with tics.