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S Valenti

Publications and source records attributed to S Valenti.

At least 37 records · Page 2Linked to original sources

Decreased steroidogenesis and cAMP production in vitro by leydig cells isolated from rats made hypothyroid during adulthood.

UNLABELLED: The Leydig cell function of adult male rats made hypothyroid with 6-propyl-2-thiouracil (6-PT, 0.1% w/v in drinking water for 1 month) was studied and compared with that of age-matched controls. After 6-PT treatment, a slight, non-significant decrease in serum testosterone was observed, but no changes in testis weight or number of Leydig cells were noted. The in vitro function of Leydig cells was therefore investigated during incubation for 3 h in the presence or absence of several stimuli: LH (30 mIU/mL), forskolin (FK 1 microM), isobutylmethylxanthine (IBMX, 100 microM), GnRH (100 nM) or FK 1 microM + IBMX 100 microM. Irrespective of the stimulus, cells from hypothyroid rats secreted less cyclic AMP, 17-hydroxyprogesterone, androstenedione and testosterone. No differences in LH receptors were noted between the groups. Prolonged incubation with triiodothyronine (5-250 ng/mL) or thyroxine (5-250 ng/mL) for 3, 16, 24 or 48 h did not affect testosterone secretion in either group; however, administration of IGF-I (8 ng/mL for 24 h) resulted in increased spontaneous and stimulated testosterone production in both groups. However, when hypothyroid animals were supplemented in vivo with thyroxine a full recovery of Leydig cell function in vitro was noted. IN CONCLUSION: (1) Leydig cells from rats made hypothyroid during adulthood produce less testosterone in vitro, both spontaneously and in response to cAMP and non-cAMP-mediated stimuli; (2) this is due to a reduction in cAMP production and in the activity of the enzymes in the androgen biosynthetic pathway, and not to changes in LH receptors; (3) direct administration of thyroid hormones did not improve testosterone secretion in either group, while incubation with IGF-I did.

Animals↗

Nitric oxide modulates in vivo and in vitro growth hormone release in acromegaly.

Nitric oxide (NO) has recently been shown to modulate pituitary secretion both in vivo and in vitro. The aim of this study was to investigate the effects of this chemical transmitter on spontaneous and growth-hormone-releasing hormone (GHRH)-induced growth hormone (GH) secretion in acromegalic patients, as well as from GH-secreting tumors maintained in vitro. The study was carried out in 7 acromegalic patients (46.2 +/- 2 years) and in 5 normal subjects (40.1 +/- 1.5 years). GH and prolactin (PRL) secretion were assayed during the administration of isosorbide dinitrate (ID, 5 mg, orally), an NO donor, GHRH, and ID plus GHRH. During ID, a significant (p < 0.05) increase (37%) over basal GH levels was only observed in acromegalics. There was no change in GH levels in response to GHRH or ID plus GHRH in either group. No significant change in PRL levels was observed in either group during ID, while GHRH, with or without ID, induced a slight increase in PRL levels in acromegalics only. Tumor specimens were obtained by selective transsphenoidal adenomectomy, and the cells were plated and incubated for 1, 2 and 24 h in the presence of sodium nitroprusside, a releaser of NO (SNP, 0.3 or 0.6 mM), of GHRH (10-8 M) or of both. SNP significantly (p < 0.001) increased GH levels in a dose-dependent manner (R = 0.99, p = 0.02), but was unable to modify the GH response to GHRH. In acromegalics, a significant correlation (R = 0.822, p < 0.045) and a correlation near the limit of significance (R = 0.73, NS) were observed respectively between the in vivo GH response to ID and the in vitro response to SNP at 24 h. No significant effect was observed on PRL secretion during SNP incubations, while GHRH produced a significant increase in PRL after 2 and 24 h incubation in acromegalics. These observations indicate that NO plays a stimulatory role in vivo and in vitro on GH secretion in acromegalic patients.

Acromegaly↗

Melatonin receptors are present in adult rat Leydig cells and are coupled through a pertussis toxin-sensitive G-protein.

Previous studies have suggested that melatonin (MLT) acts directly on rat Leydig cells by modulating androgen production. In the present study, the site of action of MLT was investigated. The binding of 2-[125I]iodomelatonin (125I-MLT; 7-240 pmol/l) to Leydig cell membrane fragments was tested in the presence or absence of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S; 50 mumol/l). Saturation studies and Scatchard analysis revealed the existence of a high-affinity binding site with a Bmax of 46.70 +/- 3.50 fmol/mg protein and a Kd of 88.70 +/- 6.20 pmol/l; treatment with GTP-gamma-S reduced the concentration of 125I-MLT binding sites (Bmax 34.03 +/- 4.50), while increasing the Kd to 106.5 +/- 2.61 pmol/l. Pretreatment of the cells with pertussis toxin (PTX; 10 ng/ml for 16 h) resulted in a decreased binding of 125I-MLT and a lack of effect of GTP-gamma-S. Moreover, the effect of MLT on testosterone secretion induced by LH (30 mIU/ml), forskolin (1 mumol/l) and LHRH (100 nmol/l) was studied after 3-h incubation of cells which had been precultured with or without PTX. The inhibition of testosterone secretion due to MLT administration was eliminated by PTX pretreatment during forskolin and LH, but not during LHRH administration. However, 17-hydroxyprogesterone levels were higher in all groups incubated in the presence of MLT, irrespective of PTX pretreatment. Our data suggest that: (a) MLT receptors are present on the membranes of adult rat Leydig cells; (b) they couple through PTX-sensitive G-protein-coupled binding sites; (c) the mechanism by which MLT blocks 17-20 desmolase enzymatic activity (thus leading to increased 17-hydroxyprogesterone levels), and testosterone secretion during LHRH stimulation is likely to depend on one or more different mechanism(s) of action.

Animals↗

Effects of sumatriptan on growth hormone releasing hormone-stimulated growth hormone secretion in acromegaly.

Sumatriptan (SU), a specific 5-HT1D receptor agonist, was recently shown to be able to increase growth hormone (GH) levels in normals, but not in acromegalics, while no effect was seen on prolactine (PRL). SU is also able to produce an increase in GH response to growth hormone releasing hormone (GHRH) in prepubertal children. In this study we investigated whether SU administration influences GHRH-induced GH secretion in 8 acromegalics, and 6 age-matched normal volunteers, as a control group. We evaluated the effects of SU (6 mg s.c.) or placebo (PL) administration on GHRH (1 microgram/kg bw i.v.)-induced GH and PRL secretion. After SU priming the GH response to GHRH did not changed in acromegalics, but significantly decreased in controls, in comparison with that observed after PL plus GHRH. In acromegalics, no difference in GH peak was seen after SU plus GHRH and PL plus GHRH, nor was any difference seen in AUC between tests. In controls, no difference was seen in GH peaks, while SU priming significantly (P < 0.03) decreased the AUC 90-120 min of GH after GHRH administration. In acromegalics, SU did not change the slight GHRH-induced increase in PRL levels. Our study documents that 5-HT1 D receptors do not interfere with GHRH-stimulated GH secretion in acromegalic subjects. In normals, SU is able to decrease GH response to GHRH, thus confirming that 5-HT1D receptors are able to modulate GH secretion in normals.

Acromegaly↗

Lack of effect of desmopressin on ACTH and cortisol responses to ovine corticotropin-releasing hormone in anorexia nervosa.

Both arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH) are involved in the release of ACTH in man. Desmopressin (DDAVP), a synthetic analogue of AVP, has been shown to have a CRH-like action (able to promote ACTH and cortisol release) in animals but not in normal man. Nevertheless, DDAVP is able to release ACTH and cortisol in ACTH-dependent Cushing's disease. We studied eight anorexia nervosa (AN) patients [as AN is a condition in which chronic activation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly reported] in a refeeding phase of the disease, to evaluate whether, after weight gain, ACTH and cortisol response to ovine corticotropin-releasing hormone (oCRH) [1 microgram i.v. DDAVP alone and as pretreatment to oCRH (1 microgram kg-1 BW i.v.)-induced secretion of ACTH and cortisol. We studied six normal women as control subjects. No significant differences in ACTH and cortisol responses to oCRH were found between AN patients and control subjects. DDAVP was not able to stimulate ACTH or cortisol release in AN patients or in control subjects, but in the latter it was able to significantly enhance (P < 0.05) ACTH [area under curve (AUC): 590.0 +/- 104.4 pmol L-1 120 min-1] and cortisol (AUC: 28899.0 +/- 6935.2 nmol L-1 120 min-1) responses to oCRH (ACTH AUC: 325.7 +/- 101.7 pmol L-1 120 min-1, cortisol AUC: 14197.4 +/- 2930.0 nmol L-1 120 min-1). The present data show that DDAVP does not stimulate ACTH and cortisol in AN patients or, as previously reported, in normal subjects. However, DDAVP is able to enhance ACTH and cortisol release after oCRH administration in normal subjects but not in AN patients. This finding could be due to a down-regulation of hypophyseal DDAVP V3 receptors in AN as a direct consequence of the hypercortisolaemic status usually present.

Adolescent↗

Mixed infection by Staphylococcus and Candida, and Wegener's granulomatosis.

We describe the case of a patient who initially presented with pneumonia from Staphylococcus aureus and Candida parapsilosis, which was resolved with antibiotic treatment, but reappeared 6 months later as full-blown Wegener's granulomatosis. The possible pathogenetic correlations between infective agents, in particular Staphylococcus aureus and Candida, and Wegener's granulomatosis are discussed.

Adult↗

[Sudden and unusual onset of penile plastic induration in 2 patients neurosurgically treated for pituitary macroadenoma].

Induratio penis plastica (IPP) or Peyronie disease is characterized by the developing of fibrotic plaques in the tunica albuginea of penis, that in the latter stages can lead to impotence. The etiology of this disease is still unknown even if various factors such as inflammation, autoimmunity or traumas are involved. Usually it occurs after 40 years of age, even if cases in young patients have been described. The onset of IPP can be acute in about 50% of the patients, while in the others it is characterized by a chronic but progressive progress. In this work, we describe the cases of two patients 52 and 66 years old, who arrived to our department for a decrease of libido and sexual potency in the last months. The patients were not smokers and took no drugs and they had never complain symptoms and signs of IPP. In both subjects an endocrine pattern compatible with partial hypopituitarism was present and in the first patient it was associated with an ACTH-dependent hypercortisolism. Pituitary imaging with MRI showed in both patients the presence of a mass compatible with macroadenoma, that in the first patient showed characteristic of invasiveness. Both subjects underwent transphenoidal neurosurgery with the exeresis of the neoplasia, with resolution of the secondary hypogonadism and reappearance of the sexual potency. With the resume of sexual activity the patients complained the appearance of painful penis bending during erection. Dynamic echographic evaluation of the penis with 7.5 Mhz linear probe, after the intracavernous injection of prostaglandin E1 10 micrograms, showed in both patients the presence of a hyperechogenic plaque in the tunica albuginea compatible with IPP. Both patients underwent successfully surgery for the excision of the plaque and the apposition of a patch of dura mater. The authors want to underlie as the onset of IPP can be sudden, promoted by the resolution of the hypogonadism secondary to pituitary neoplasia, and contemporary to the normalization of testosterone levels.

Adenoma↗

P0.1 is a useful parameter in setting the level of pressure support ventilation.

OBJECTIVE: The purpose of this study was to investigate whether changes in breathing pattern, neuromuscular drive (P0.1), and the work involved in breathing might help to set the individual appropriate level of pressure support ventilation (PSV) in patients with acute respiratory failure (ARF) requiring ventilatory assistance. DESIGN: A prospective, interventional study. SETTING: An 8-bed multidisciplinary intensive care unit (ICU). PATIENTS: Ten patients with ARF due to adult respiratory distress syndrome (ARDS), sepsis or airway infection were included in the study. Chronic obstructive pulmonary disease (COPD) patients with acute exacerbation were excluded. None of these patients was in the weaning process. INTERVENTIONS: We found a level of pressure support able to generate a condition of near-relaxation in each patient, as evidenced by work of breathing (WOB) values close to 0 J/1. This level was called PS 100 and baseline physiological measurements, namely, breathing pattern, P0.1 and WOB were obtained. Pressure support was then reduced to 85%, 70%, and 50% of the initial value and the same set of measurements was obtained. MEASUREMENTS AND RESULTS: Flow (V) was measured by a flow sensor (Varflex) positioned between the Y-piece of the breathing circuit and the endotracheal tube. Tidal volume was obtained by numerical integration of the flow signal. Airway pressure (P(aw)) was sampled through a catheter attached to the flow sensor. Esophageal pressure (Pes) was measured with a nasogastric tube incorporating an esophageal balloon. The esophageal balloon and flow and pressure sensors were connected to a portable monitor (CP 100 Bicore) that provided real-time display of flow, volume, P(aw) and Pes tracings and loops of Pes/V, P(aw)/V and V/V relationships. The breathing pattern was analyzed from the flow signal. Patient work of breathing (WOB) was calculated by integration of the area of the Pes/V loop. Respiratory drive (P0.1) was measured at the esophageal pressure change during the first 100 ms of a breath, by the quasi-occlusion technique. When pressure support was reduced, we found that the respiration rate significantly increased from PS 100 to PS 85, but varied negligibly with lower pressure support levels. Tidal volume behaved in a similar way, decreasing significantly from PS 100 to PS 85, but hardly changing at PS 70 and PS 50. In contrast, WOB and P0.1 increased progressively with decreasing pressure support levels. The changes in WOB were significant at each stage in the trial, whereas P0.1 increased significantly from PS 100 at other stages. Linear regression analysis revealed a highly positive, significant correlation between WOB and P0.1 at decreasing PSV levels (r = 0.87), whereas the correlation between WOB and ventilatory frequency was less significant (r = 0.53). No other correlation was found. CONCLUSIONS: During pressure support ventilation, P0.1 may be a more sensitive parameter than the assessment of breathing pattern in setting the optimal level of pressure support in individual patients. Although P0.1 was measured with an esophageal balloon in the present study, non-invasive techniques can also be used.

Adolescent↗

The effect of non-steroidal antiandrogen flutamide on luteinizing hormone pulsatile secretion in male-to-female transsexual subjects.

We evaluated LH pulsatile patterns before and 4 weeks after the oral administration of flutamide (750 mg/day) in 9 male-to-female transsexuals (age range 17-28 yr) requesting gender reassignment. Flutamide was given to explore the feedback role of androgens on the LHRH-LH unit in LH pulsatility in transsexuals. Seven normal age-matched men served as a control group, without receiving flutamide, due to ethical considerations. LH pulsatility was evaluated on samples collected every 15 min for 360 min. FSH, PRL, cortisol, SHBG and sex steroids were evaluated on pooled samples. LH pulses were analyzed by the Santen and Bardin algorithm, slightly modified. No differences in FSH, PRL, total- or free-testosterone, estradiol and SHBG levels were noted between transsexuals and controls. Normal circadian cortisol decline was observed in all subjects. Mean LH levels (p < 0.05) and LH pulses (p < 0.01) were significantly lower in transsexuals. Flutamide induced an increase in mean LH and testosterone levels (p < 0.01). After flutamide administration there was an increase in LH pulse frequency (P < 0.01) and the frequency and amplitude of LH pulses in transsexuals were restored to levels observed in controls. No differences in FSH, PRL or estradiol levels were found after flutamide. These data suggest that a decrease in LH pulse frequency could be an endocrine marker in male-to-female transsexuals. An increase in endogenous androgen negative feed-back could be speculated in these subjects. However, normal testosterone levels indirectly suggest that a normal that a normal qualitative LH secretion is maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A technique for sorting rat gonadotropes using anti-LH or anti-FSH antibodies covalently attached to magnetic beads.

A technique for sorting live LH- and FSH-secreting cells was developed. After enzymatic dispersion, a suspension of pituitary cells from male rats castrated 7 days earlier was incubated in potassium chloride (KCI 50 mmol/l) for 30 min and gonadotropin outflow was provoked. Then, considering either LH or FSH as temporary surface markers, we positively selected the secreting cells by means of antibodies toward either LH (anti-LH beads) or FSH (anti-FSH beads) covalently attached to magnetic beads. The spontaneous secretion of LH and FSH overnight and the release induced by KCI the following morning were calculated. A population enriched in gonadotropes (16% of the total) able to secrete both gonadotropins was selected by means of anti-LH beads; this released 7 times as much LH as non-selected cells. A similar population (14% of the total) was selected by means of anti-FSH-coated beads; this produced 3.3 times as much LH as non-selected cells. In some experiments, the cells not previously sorted with anti-LH-coated beads were further incubated in the presence of anti-FSH beads, in an attempt to isolate a population secreting only FSH. A limited number of cells were sorted (6% of the total cells), able to produce both gonadotropins, but with a lower LH/FSH ratio. Similarly, those cells excluded by the selection with anti-FSH beads were further incubated with anti-LH beads, with a view to obtaining only-LH-secreting cells. However, both gonadotropins were still secreted by these cells (8% of the total), which had the highest LH/FSH ratio. In conclusion, fractions from castrated male rats that are enriched in gonadotropes contain cells that secrete both gonadotropins in vitro. The secretion of LH is prevalent. However, differences in the LH/FSH ratio between the populations sorted and changes from spontaneous to stimulated release are observed. This suggests that some gonadotropes might 'specialize' in releasing LH and others in releasing both LH and FSH.

Animals↗

In vitro acute and prolonged effects of melatonin on purified rat Leydig cell steroidogenesis and adenosine 3',5'-monophosphate production.

The effects of melatonin (MLT; 4.3 pM to 4.3 microM) on rat Leydig cell steroidogenesis and cAMP production were investigated during 3-h LH (30 mIU/ml) stimulation. Having noted a dose-dependent inhibition of testosterone (T) release, we also tested MLT in the presence of the cAMP activator forskolin (1 microM), the phosphodiesterase inhibitor isobutylmethylxanthine (100 microM), a combination of these two, and LHRH (100 nM), a non-cAMP-mediated stimulus. Regardless of the stimulus, levels of T, androstenedione, and cAMP were reduced, whereas that of 17-hydroxyprogesterone was enhanced. Cells were also tested after prolonged exposure to MLT (215 nM for 16 h). When compared with data from cells not preincubated with MLT, cAMP and T levels were 30% higher during LH stimulation (30 mIU/ml); comparable during treatment with forskolin (1 microM), isobutylmethylxanthine (100 microM), or their combination; and reduced during LHRH (100 nM). Scatchard analysis did not reveal changes in LH receptors during prolonged MLT exposure. Our data show that MLT acutely reduces cAMP- and non-cAMP-stimulated T. This effect is linked in part to reduced cAMP production and in part to reduced 17-20-desmolase enzymatic activity, which, however, can occur even with non-cAMP-mediated stimulation. On the other hand, prolonged exposure to MLT results in sensitization of the LH-dependent adenylate cyclase activity.

Androgens↗

Delayed puberty in males with beta-thalassemia major: pulsatile gonadotropin-releasing hormone administration induces changes in gonadotropin isoform profiles and an increase in sex steroids.

Patients with beta-thalassemia major often have pubertal delay, the etiology of which has not been fully elucidated. We investigated the pituitary-gonadal response to short-term subcutaneous pulsatile gonadotropin-releasing hormone (GnRH) administration (150 ng/kg body weight every 120 min for 7 days) in five young males (aged 13.6-19.0 years) affected by beta-thalassemia major and presenting signs of delayed puberty. Immunoreactive and bioactive gonadotropin levels were determined and their isoform profiles were examined, before and after GnRH treatment, in a pool of samples collected every 15 min for 240 min. Testosterone, androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone and 17 beta-estradiol were measured as markers of gonadal function on days 0, 1, 3, 5 and 7 of treatment. Five patients (aged 16.9-26.8 years) with confirmed diagnosis of idiopathic hypogonadotropic hypogonadism who were starting pulsatile GnRH therapy were also studied in the same protocol. Increased sex steroid levels were observed in both groups as a result of treatment. On day 7, the thalassemic patients had increased bioactive luteinizing hormone (LH) and follide-stimulating hormone (FSH), although immunoreactive LH and FSH were comparable to day 0. Moreover, fewer acidic and more basic immunoreactive and bioactive isoforms were noted in LH profiles on day 7. Similar results were observed in hypogonadal patients, who also had increased immunoreactive LH and FSH values. We suggest that the early stage of delayed puberty in thalassemia might be characterized by a neuroendocrine dysfunction resulting in an impaired hypothalamic GnRH release, which is inadequate for a proper pituitary stimulation. Pulsatile GnRH treatment seems to re-establish partially the correct pituitary-gonadal function.

17-alpha-Hydroxyprogesterone↗

Treatment of acromegaly with octreotide: effectiveness and tolerability of its pulsatile administration by portable pump.

This study was undertaken to evaluate effectiveness and tolerability of octreotide administered in active acromegaly by pulsatile means and compare these data with intermittent three-times-a-day therapy. We studied 13 acromegalics with active disease. All patients received octreotide subcutaneously administered in a pulsatile way using a portable pump delivering 25 micrograms every 120 minutes and in an intermittent way (100 micrograms three times daily) (TID). From pretreatment values (56.5 +/- 13.4 micrograms/L) the 24-h integrated mean GH levels (IC-GH) were significantly reduced both during pulsatile and TID octreotide administration (P < 0.01). IC-GH was significantly lower during pulsatile therapy (17.0 +/- 5.2 micrograms/L) than during TID (22.0 +/- 11.5 micrograms/L; P < 0.05). Before octreotide, IGF-I levels were 669.8 +/- 85.7 micrograms/L; during octreotide therapy they were reduced in 12/13 patients (TID 340.2 +/- 41.5 micrograms/L, pulsatile 338.1 +/- 55.3 micrograms/L; P < 0.01). A correlation between IC-GH and IGF-I levels was observed only during TID administration of octreotide (R = 0.652; P < 0.05). The 24-hour GH pattern fluctuated widely before the start of octreotide therapy. During TID administration, GH levels tended to rise again before the following octreotide injection; this did not occur during pulsatile therapy. Side effects were fewer during pulsatile (15%) than TID (31%) octreotide administration (NS). Asymptomatic gallstones appeared in 1 patient. In conclusion subcutaneous pulsatile octreotide administration in acromegalic patients by means of a small portable pump seems able to produce, a steadier control of GH-IGF-I hypersecretion and fewer side effects than TID administration at same dosage.

Acromegaly↗

[Tracheal intubation in a case of Still's disease].

The authors report the case of a patient with juvenile rheumatoid arthritis (Still's disease) who underwent laparotomic hysterectomy under general anesthesia. Tracheal intubation was performed with the aid of a fibroscope, as recommended in the literature, given that impairment of the cervical spine and the temporo-mandibular joint made it extremely unlikely that direct laryngoscopy could be performed. The authors also report the methods recommended by other authors in order to guarantee a sufficiently deep anesthetic plane together with patency of the airways in patients suffering from Still's disease.

Adult↗

Sumatriptan does not stimulate PRL and GH secretion in acromegaly.

OBJECTIVE: Serotoninergic receptors are involved in the regulation of PRL and GH secretion. We studied the effects of sumatriptan, a new 5-HT1D receptor agonist, on PRL and GH secretion in active acromegaly. EXPERIMENTAL DESIGN: After their informed consent, all subjects were submitted to sumatriptan or placebo administration in single blind and in a random order. The time interval between the tests was of 7 days. ENVIRONMENT: We examined all patients in the morning, after 12 hours of fasting. All subjects were in recumbent position during the tests. Pulse rate and blood pressure were monitored during the test. SUBJECTS: Eight acromegalics (42-65 years) and 10 age-matched (33-63 years) normal subjects. PROTOCOL: Blood samples were taken after needle insertion kept patent by slow saline solution infusion. PRL and GH secretion were evaluated after sumatriptan (6 mg sc) and placebo. Blood samples were taken before (45, 15 and 0 minutes) and every 15 minutes for 2 hours after sumatriptan or placebo administration. RESULTS: No significant changes in PRL secretion were observed after sumatriptan in both groups of subjects. A significant increase in GH levels after sumatriptan was observed in controls but not in acromegalics. An age-related negative trend in GH response to sumatriptan was observed in controls. CONCLUSIONS: Our study indicated that 5-HT1D receptors are not involved in PRL and GH secretion in middle-aged acromegalics.

Acromegaly↗

[Anorexia nervosa: a follow-up of nutritional, hormonal and psychiatric parameters].

Well known is the need to treat "acute onset" Anorexia Nervosa in care units. Nevertheless even the "successfully treated" patients show a very high percentage of relapse. The aim of our study has been to revalue different clinical, nutritional (hemoglobin, transferrin, IGF1), hormonal (thyroid function, gonadotropins) and psychiatric (EDI: Eating Disorder Inventory Test) parameters in a group of nineteen women aged 20-34 years (median 27 years) admitted to our department 1-11 years (median 6 years) before for anorexia nervosa treatment. On admission their weight loss was -33% +/- 10% according to Ideal Body Weight (IBW); a "low T3 syndrome" was present and all the patients not treated with estro-progestins were amenorrhoic. After a long hospitalization (median 51 days) the patients showed a significant decrease in weight loss (25% +/- 6%; p < 0.01). At follow-up seventeen patients had a weight better than at discharge (13% +/- 12%; p < 0.01) and 9/17 patients non treated with estro-progestins had spontaneous menses. Nutritional (hemoglobin*: 13 +/- 0.2 g%, transferrin*: 313 +/- 57 mg%, IGF-1: 187 +/- 15 ng/ml) and hormonal (LH*: 9.4 +/- 1 mUI/ml, FSH*: 15 +/- 1.3 mUI/ml, T3: 1 +/- 1 ng/ml) parameters were significantly improved (*p < 0.01, p < 0.05) compared to those at admission (hemoglobin: 12 +/- 0.2 g%, transferrin: 218 +/- 58 mg%, IGF-1: 154 +/- 21 ng/ml, LH: 5.6 +/- 0.8 mUI/ml, FSH: 9.5 +/- 1 mUI/ml, T3: 0.8 +/- 1 ng/ml). The EDI test has shown a persistence of anorexic condition ("overt" or latent) in 2/3 of patients. This study confirms the endocrine and nutritional modifications of anorexia nervosa and underlines the persistence of psychiatric ones in a great number of patients including the "clinically cured", justifying long-term follow-up and the high percentage of disease relapse.

Acute Disease↗

Opioid tonus and luteinizing hormone secretion in anorexia nervosa: priming effect with serotonin precursor L-5-hydroxytryptophan during pulsatile gonadotropin-releasing hormone administration.

In anorexia nervosa (AN) luteinizing hormone (LH) release is often impaired during opioid blockade. We investigated whether a restoration of the endogenous sex steroid milieu, together with a rise in central serotonergic tone, could increase LH responsiveness to Naloxone (NAL) in seven young women affected by AN. The spontaneous pulsatility of gonadotropins and their response to gonadotropin-releasing hormone (GnRH) and NAL challenges were tested before and after 13 days of pulsatile GnRH treatment and oral administration of L-5-hydroxytryptophan. Low and unpulsatile gonadotropin levels, responsive to GnRH, but not to NAL, were found before treatment. Pulsatile GnRH brought about a quasi-normal secretory pattern and 17 beta-estradiol increased to preovulatory levels in six of seven patients. On day 13 the lack of response to NAL administration was still present, however. A neuroendocrine disorder seems to be present in AN, which appears more complex than in other forms of hypothalamic amenorrhea.

5-Hydroxytryptophan↗

Acute buflomedil intoxication: a life-threatening condition.

A 15-year-old girl was admitted to ICU in a comatose state. She presented with mydriasis, areflexia, hypoxemia and seizures. She was immediately intubated and connected to a ventilator. The seizures were reversed with intravenous diazepam. CT scan was negative. EEG showed a diffuse fast activity and theta waves with spikes in the anterior and temporal regions, bilaterally. The gastric lavage was suggestive of drug ingestion. The patient completely recovered after 6 h of mechanical ventilation and supportive management. Mydriasis was still present after the resolution of neurological symptoms. The girl told us she had ingested 10 tablets (3 g-55 mg/kg) of Loftyl (buflomedil) for suicidal intention. The buflomedil concentrations at 2-3 h from ingestion were 24.8 mg/l in the blood, 324.4 mg/l in the urine and 6.9 mg/l in the gastric content. The p-desmethyl metabolite was also identified in the urine. Buflomedil is a rheological agent largely used as a vasodilator in some European countries. Some recent reports have emphasized the risk of acute intoxication with this drug. Relatively low doses (50-60 mg/kg) have been associated with an important neurological toxicity and a high mortality. We suggest that the clinical picture we observed might be related to a neuroleptic-type action of buflomedil. We bring to attention the risk of a large, uncontrolled diffusion of a drug capable to cause serious consequences at relatively low doses.

Acute Disease↗