Controlling catheter-related bloodstream infections through a multi-centre educational programme for intensive care units.

BACKGROUND: Bloodstream infections (BSIs) associated with insertion and maintenance of central venous catheters (CRBSIs) are the most frequent causes of healthcare-associated infections in intensive care units (ICUs). They are responsible for increased length of hospital stay and additional healthcare costs. AIM: To investigate whether an educational programme aimed at healthcare workers resulted in a significant change in the level and trend of infections. METHODS: The research was conducted in five Italian ICUs from July 2012 to August 2014. Surveillance and educational interventions to control infections were applied. Compliance with hand hygiene procedures was assessed via relative risk and 95% confidence interval. Interrupted time-series analysis was used to investigate the change in level and trend of infection during the intervention. FINDINGS: Compliance with hand hygiene procedures improved during the intervention for all staff groups, but physicians showed the lowest compliance rates (nurses from 52.4% to 92.1%; nurse aides from 71.0% to 92%; physicians from 71.0% to 92%; P < 0.001). Significant reductions of 21-55% in CRBSI were observed during the intervention. Small improvements in the monthly infection trend were also observed, but these were not statistically significant. CONCLUSION: An educational programme focusing on general good infection control practice, rather than CVC care bundles, led to a decreased CRBSI rate, even if the improvement was not sustained over time. Continuous performance feedback should be provided to promote long-term adherence to guidelines among all health workers.

Soy isoflavones, lactobacilli, Magnolia bark extract, vitamin D3 and calcium. Controlled clinical study in menopause.

AIM: Affective and behavioural disorders possibly concomitant to the vasomotor menopausal symptoms worsen quality of life. A rational formulation containing soy isoflavones (60 mg), lactobacilli (500 millions spores), calcium (141 mg) and vitamin D3 (5 microg) was added of Magnolia bark extract (60 mg) and magnesium (50 mg) (Estromineral serena, ES). The Magnolia extract active principles interact with GABA system and exhibit a sedative central action. Magnesium intervenes in enzymatic reactions of the energetic metabolism and protects the bone integrity. Aim of this controlled study was to compare the clinical activity and safety of ES versus calcium+vitamin D3 (Ca+D) in menopause. METHODS: A controlled, randomised, multicentre study was carried out in symptomatic menopausal women with sleep or mood alterations. Women received 1 tablet/day of ES or Ca+D for 24 weeks. Symptoms during the treatment and final judgements on efficacy and acceptability were evaluated. RESULTS: Eighty-nine women (44 ES and 45 Ca+D, mean age 53.8 years, in menopause since 56.6 months) participated to the study. Flushing, nocturnal sweating, palpitations, insomnia, asthenia, anxiety, mood depression, irritability, vaginal dryness, dyspareunia, and libido loss, significantly decreased in severity and frequency during ES versus Ca+D treatment even since the fourth week. Woman wellbeing (good/very good 66.7% vs 20%) judgement on efficacy (72.7% vs 17.1%) and acceptability (93.9% vs 31.4%) were significantly better for ES. CONCLUSIONS: The controlled study showed the efficacy of Magnolia extract and magnesium on psycho-affective and sleep disturbances in menopause, in addition to the effects of isoflavones on vasomotor symptoms. A global natural approach to menopause with ES evidenced its therapeutic usefulness and safety.

Verticillium Wilt of Xanthium italicum Caused by Verticillium dahliae in Italy.

During the late summer of 2003, a wilt disease of the weed Italian cockleburr (Xanthium italicum Mor.) was observed in the Basilicata Region of southern Italy. Diseased plants were growing near an apricot orchard in which some trees were severely affected by Verticillium wilt. The most characteristic symptoms of the wilt disease affecting Italian cockleburr were yellowing, stunting, and gradual wilting. Also, diagonal and cross sections of stems revealed brown discoloration of their vascular tissues. To elucidate the etiology of the disease, we attempted detection and identification of the causal agents using traditional and polymerase chain reaction (PCR)-based methods. Small pieces of petiole and stem tissues from diseased and asymptomatic plants were surface disinfested in NaOCl solution, rinsed in sterile distilled water, blotted dry, and plated onto water agar (WA) medium. Following incubation at 22°C, the emerging colonies were transferred to potato dextrose agar (PDA). Verticillium dahliae (one isolate) was consistently identified on the basis of its morphological features according to the description of Smith (2). Using PCR assays with the primer pair ITS5/ITS4 (3), which are directed to fungal nuclear ribosomal DNA (rDNA) repeat sequences, an amplification product of approximately 560 bp was obtained by using total DNA extracted from wilt-affected Italian cockleburr plant tissues (five plants examined) as well as fresh mycelium from the V. dahliae-infected Italian cockleburr pure culture-maintained isolate mentioned above. No visible PCR products were obtained with total DNA from asymptomatic Italian cockleburr plants. Sequence analysis of the ITS5/ITS4 amplicons revealed no differences in their nucleotide positions. The obtained sequence of the V. dahliae-infected Italian cockleburr isolate (GenBank Accession No. AJ865691) was then used as query sequences in a BLAST 2.0 search (1). Sequence of the southern Italian isolate proved to be identical to that of the Greek strain "76 Greece" of V. dahliae (GenBank Accession no. AF104926). To prove Koch's postulates, 10 healthy Italian cockleburr seedlings were experimentally inoculated by dipping trimmed roots in a single-conidial suspension (1.5 × 106 CFU/ml) obtained from 10-day-old colonies of the V. dahliae-infected Italian cockleburr pure culture-maintained isolate. After 4 weeks, all inoculated Italian cockleburr plants showed symptoms identical to those of naturally infected field-grown plants. V. dahliae was consistently reisolated from inoculated plants. Additional inoculation experiments revealed that pepper and eggplant were also susceptible to the V. dahliae-infected Italian cockleburr isolate showing typical Verticillium wilt symptoms. To our knowledge, this is the first report of the occurrence of Verticillium wilt of X. italicum. References: (1) S. F. Altschul et al. Nucleic Acids Res. 25:3389, 1997. (2) H. C. Smith. N.Z. J. Agric. Res. 8:450, 1965. (3) T. J. White et al. Pages 315-322 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990.

Intranasal administration of neostigmine potentiates both intravenous and intranasal growth hormone (GH)-releasing hormone-induced GH release in short children.

Administration of cholinergic agonists increases both basal and GH-releasing hormone (GHRH)-induced GH secretion, probably acting via inhibition of endogenous somatostatin release. The aim of our study was to verify in two groups of children with idiopathic short stature the effect of intranasal administration of neostigmine (inNS; 3 mg), a cholinesterase inhibitor, on basal GH levels as well as on the somatotroph response to GHRH when the peptide was administered either iv (ivGHRH; 1 microgram/kg) or intranasally (inGHRH; 10 micrograms/kg). In group A (n = 6; age, 10.6-16.0 yr) inNS induced a significant GH increase [inNS vs. saline, area under the curve (AUC; mean +/- SEM), 263.7 +/- 60.2 vs. 73.8 +/- 3.1 micrograms/L.h; P less than 0.03] and potentiated the somatotroph response to ivGHRH (inNS with ivGHRH vs. ivGHRH, 1316 +/- 183.0 vs. 644.9 +/- 154.5 micrograms/L.h; P less than 0.03). In group B (n = 6; age, 11.5-15.9 yr) ivGHRH induced a GH rise clearly higher than that induced by inGHRH (604.2 +/- 154.3 vs. 137.1 +/- 28.2 micrograms/L.h; P less than 0.03). Administration of inNS induced a GH rise similar to that occurring after inGHRH (AUC, 239.2 +/- 69.5 micrograms/L.h) and markedly increased the inGHRH-induced GH response (482.4 +/- 103.6 micrograms/L.h; P less than 0.05 and 0.03 vs. inNS and inGHRH, respectively), so that it overlapped with that induced by ivGHRH alone. In conclusion, cholinergic agonists such as neostigmine are able to increase both basal and GHRH-induced GH secretion in short children even when given intranasally. Combined intranasal administration of neostigmine and GHRH (10 micrograms/kg) is able to induce a GH rise similar to that induced by ivGHRH alone (1 microgram/kg), suggesting the potential usefulness of this combination cocktail and route of administration for the treatment of short stature.

Long-lasting prolactin-lowering effect of cabergoline, a new dopamine agonist, in hyperprolactinemic patients.

The new long-acting ergoline derivative cabergoline was given orally in a single dose of 300 micrograms to 15 hyperprolactinemic patients (including 4 acromegalic patients, 2 of whom were dopamine responsive). Serum PRL and GH levels were determined before and 3, 4, and 6 h and 1, 2, 3, 4, 5, 6, and 7 days after treatment. A control test with a single oral dose of 2.5 mg bromocriptine was also performed; serum PRL and GH levels were measured at the same time intervals for 2 days. Cabergoline induced a marked fall in serum PRL which began within 3 h and continued for 7 days. The maximal decrease ranged between -49.2% and -55.2% and occurred after 2-5 days. This maximal effect was only slightly less than that 6 h after bromocriptine treatment (-63.8%). After cabergoline treatment, serum GH levels did not change significantly in either nonacromegalic or acromegalic patients, whereas the two dopamine-responsive acromegalic patients had a marked GH fall after bromocriptine. A moderate blood pressure decrease, more evident in the standing position, occurred after both cabergoline and bromocriptine treatments. The only symptomatic side-effect was orthostatic hypotension after cabergoline in an elderly woman. These data indicate that cabergoline has potent and prolonged dopaminergic activity and may prove suitable for once weekly treatment of hyperprolactinemic patients.

Somatotropic function in short stature: evaluation by integrated auxological and hormonal indices in 214 children. The Italian Collaborative Group of Neuroendocrinology.

GH secretion was evaluated in 214 children and adolescents (age, 5-16 yr; 160 males and 54 females) with short stature (height, < or = 5th percentile) by assessing mean spontaneous overnight GH concentration (normal values, > or = 3 and 3.9 micrograms/L for prepubertal and pubertal subjects, respectively) and responsiveness to stimulation with GH-releasing hormone combined with pyridostigmine (normal peak values, > or = 20 micrograms/L). Plasma insulin-like growth factor-I (IGF-I) was also measured. According to their GH secretory status, children were grouped as follows: group I, 154 subjects with normal spontaneous and stimulated GH (43 slow-growing and 111 normally growing); group II, 39 subjects with low spontaneous, but normal stimulated, GH (27 slow-growing and 12 normally growing); group III, 18 slow-growing subjects with low spontaneous and stimulated GH; and group IV, 3 subjects with normal spontaneous, but low stimulated, GH. The following conclusions were drawn. 1) Forty-five slow-growing subjects (21% of the total sample) had GH deficiency; 27 (12.6%) belonged to group II (with a preserved GH pituitary reserve, denoting a hypothalamic dysfunction) and 18 (8.4%) to group III (with a reduced GH pituitary reserve). 2) Forty-three slow-growing children in group I had normal GH secretion but low mean IGF-I, which may indicate nutritional problems or a biologically hypoactive GH molecule. 3) The remaining 111 subjects in group I (52%), with normal growth rate, but low mean parental height, were considered as having familial and/or constitutional short stature. GH responses after pyridostigmine plus GH-releasing hormone were normal in all children with a normal growth rate. These findings show that besides clinical evaluation, the assessment of spontaneous GH secretion, GH pituitary reserve, and IGF-I concentration allows proper pathophysiological characterization of short stature. By this approach, the frequency of GH deficiency in our sample was higher than commonly thought.

Effect of 15-day treatment with growth-hormone-releasing hormone alone or combined with different doses of arginine on the reduced somatotrope responsiveness to the neurohormone in normal aging.

It is well known that both spontaneous and growth hormone-releasing hormone (GHRH)-stimulated GH secretion undergo an age-related decrease; in addition, there is supportive evidence that the GH hyposecretory state of aging is of hypothalamic origin. The aims of the study in 35 normal elderly subjects (20 males and 15 females aged 65-89 years) were to verify whether the low somatotrope responsiveness to GHRH (1 microgram/kg) can be primed by a daily GHRH treatment and whether the potentiating effect of both high intravenous (0.5 g/kg) and low oral (8 g) doses of arginine (ARG) on GH response to GHRH is maintained with time. In group A (N = 14) the GH response to GHRH on day 1 (AUC: 373.5 +/- 78.5 micrograms.l-1.h-1) was unchanged after 7 (3720 +/- 38 micrograms.l-1.h-1) and 15 days (377.9 +/- 63.8 micrograms.l-1.h-1) of daily GHRH administration. In group B (N = 6) the GH response to GHRH co-administered with iv ARG on day 1 (1614.2 +/- 146.2 micrograms.l-1.h-1) was higher (p < 0.05) than that of GHRH alone (group A) and persisted unchanged after 7 (1514.7 +/- 366.5 micrograms.l-1.h-1) and 15 days (1631.7 +/- 379.1 micrograms.l-1.h-1) of treatment. In group C (N = 15) the GH response to GHRH co-administered with oral ARG on day 1 (950.6 +/- 219.4 micrograms.l-1.h-1) was higher (p < 0.03) than that of GHRH alone (group A) but lower (p < 0.05) than that to GHRH plus iv ARG (group B).(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone-releasing activity of growth hormone-releasing peptide-6 is maintained after short-term oral pretreatment with the hexapeptide in normal aging.

The reduced activity of the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis in aging may contribute to changes in body composition. As this GH insufficiency is due to hypothalamic pathogenesis, the availability of GH-releasing peptides (GHRPs), such as GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) which is active even after oral administration, might be useful to restore it. The aim of our study was to verify the effectiveness of oral administration of GHRP-6 in normal elderly subjects and to investigate whether its GH-releasing activity is maintained or vanishes after short-term oral treatment. Seven normal elderly women (aged 65-82 years) were studied. The effect of oral administration of 300 micrograms/kg GHRP-6 on GH secretion was investigated before and after 4 days of treatment with the hexapeptide given twice daily. The GH response to the maximal effective dose of GHRH (1 microgram/kg i.v.) also was studied. Before treatment, oral administration of 300 micrograms/kg GHRP-6 elicited a clear GH rise (peak 10.7 +/- 3.3 micrograms/l; AUC 353.1 +/- 90.6 micrograms.l-1.h-1), which was significantly higher (p < 0.01) than that induced by intravenous GHRH (peak 5.1 +/- 1.5 micrograms/l; AUC 106.5 +/- 43.9 micrograms.l-1.h-1). After 4 days of treatment with GHRP-6, the GH response to the hexapeptide was maintained, with a trend towards an increase (peak 16.8 +/- 2.9 micrograms/l; AUC 499.8 +/- 107.2 micrograms.l-1.h-1). The IGF-I levels were not increased significantly after treatment (77.1 +/- 8.4 vs 84.1 +/- 12.2 micrograms/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Separation anxiety disorder in children and adolescents: epidemiology, diagnosis and management.

This paper provides an overview of the phenomenology, longitudinal outcome data, assessment and management of separation anxiety disorder (SAD) in children and adolescents. SAD is qualitatively different from early worries, and is characterised by an abnormal reactivity to real or imagined separation from attachment figures, which significantly interferes with daily activities and developmental tasks. Different epidemiological studies indicate a prevalence of 4 to 5% in children and adolescents. In contrast to other anxiety disorders, 50 to 75% of children with SAD come from homes of low socioeconomic status. The severity of symptomatology ranges from anticipatory uneasiness to full-blown anxiety about separation, but children are usually brought to the clinician when SAD results in school refusal or somatic symptoms. School refusal is reported in about 75% of children with SAD, and SAD is reported to occur in up to 80% of children with school refusal. Longitudinal studies have suggested that childhood SAD may be a risk factor for other anxiety disorders, but whether this link is specific to, for example, panic disorder and agoraphobia, or whether SAD represents a general factor of vulnerability for a broad range of anxiety disorders is still debated. Most relevant data are reported on nonpharmacological treatments (psychoeducational, behavioural, cognitive-behavioural, family and psychodynamic), and these are the first choice approach in SAD. Controlled studies show efficacy of cognitive-behavioural therapy in children with anxiety disorders and specifically in SAD-school phobia, supporting this approach as the best proven treatment. Pharmacotherapy should be used in addition to behavioural or psychotherapeutic intervention when the child's symptoms have failed to respond to those treatments, and he/she is significantly impaired by the symptoms. Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRI) have a good adverse effect profile and may be considered as first choice drugs in SAD. When different SSRIs fail to improve symptomatology, a trial with a tricyclic antidepressant (TCA) is indicated, with careful monitoring of cardiac functioning. Because of the adverse effect profile and the potential for abuse and dependence, benzodiazepines should be used only when a rapid reduction of symptomatology is needed, until the SSRI or the TCA have begun to be effective (few weeks). Buspirone should be considered in children who have not responded to other treatments. Further research is needed to confirm efficacy of newer antidepressants (venlafaxine, mirtazapine, nefazodone) in childhood anxiety disorders.

Open trial of risperidone in 24 young children with pervasive developmental disorders.

OBJECTIVE: To describe tolerability and efficacy of risperidone in very young children with pervasive developmental disorders. METHOD: Twenty-four children aged 3.6 to 6.6 years (mean 4.6 years +/- 8 months) enrolled during 1999 and 2000 participated in a 16-week open-label trial with risperidone monotherapy. Outcome measures included the Children's Psychiatric Rating Scale (CPRS), Childhood Autism Rating Scale (CARS), Clinical Global Impression-Improvement (CGI-I), and Children's Global Assessment Scale (C-GAS). RESULTS: Two subjects did not complete the trial because of side effects. The optimal dose was 0.5 mg/day. After the treatment a 21% improvement in CPRS and a 14% improvement in CARS total scores was found. Items related to behavioral control (hyperactivity, fidgetiness, rhythmic motions) and affect regulation (lability of affect, angry affect) improved more than 25%. Based on improvement of at least 25% on the CPRS and a score of 1 or 2 on the CGI-I, eight subjects were considered responders. Functional impairment (C-GAS) improved more than 25%. Thirteen subjects (54%) were free of any side effects; in the other participants risperidone was well tolerated. Only three subjects had a weight gain greater than 10%. CONCLUSIONS: Low-dose risperidone may positively affect symptoms in young autistic children, improving disruptive/hyperactive behavior and affective dysregulation. Further controlled studies in this age group are warranted.

Adriamycin-induced histamine release from heart tissue in vitro.

It has been proven that the anthracyclines induce an important, noncytotoxic histamine release from rat peritoneal mast cells. As mast cells derived from different tissues exhibit marked heterogeneity, the effect of Adriamycin in comparison with other antineoplastic agents was tested on fragments of the right heart auricle, which contain a great number of mast cells. In this experimental model, Adriamycin induced a dose-dependent histamine release that was significantly limited by the antiexocytotic drug sodium cromoglycate. The antineoplastic agents cisplatin and 5-fluorouracil, in contrast, did not provoke any comparable histamine release. In the formulation employed in clinical settings, paclitaxel was also capable of inducing a histamine release comparable with that of Adriamycin; the exocytotic activity, however, was also evident when the tissue fragments were treated with Cremophor EL alone, without the addition of paclitaxel, whereas treatment of samples with paclitaxel dissolved in ethanol did not induce any releasing action. These data thus suggest that the secretory activity should be ascribed to the solvent Cremophor EL and not to paclitaxel. The release of histamine induced by paclitaxel in Cremophor EL/ethanol was also limited by sodium cromoglycate. These results again indicate that histamine release from mast cells derived not only from the peritoneal cavity but also from the cardiac tissue could play a role in the cardiotoxicity of anthracyclines and of paclitaxel in the clinically employed formulation.

Factors influencing hospital infection control policies in Italian hospitals.

A study was undertaken to determine the resources available in Italian hospitals for the control of nosocomial infections and the factors favouring a successful approach. During January-May 2000 a questionnaire about infection control was sent to the hospital health director of all Italian National Health System hospitals treating acute patients and with more than 3500 admissions in 1999. An active programme was defined as a hospital infection control committee (HICC) meeting at least four times in 1999, the presence of a doctor with infection control responsibilities, a nurse employed in infection control and at least one surveillance activity and one infection control guideline issued or updated in the past two years. There was a response rate of 87.5% (463/529). Almost fifteen percent (69/463) of hospitals had an active programme for Infection Control and 76.2% (353/463) had a HICC. Seventy-one percent (330/463) of the hospitals had a hospital infection control physician and 53% (250/463) had infection control nurses. Fifty-two percent (242/463) reported at least one surveillance activity and 70.8% (328/463) had issued or updated at least one guidance document in the last two years. The presence of regional policies [odds ratio (OR) 8.7], operative groups (OR 4.2), at least one full-time nurse (OR 4.6) and a hospital annual plan which specified infection control (OR 2.1) were statistically associated with an active programme in the multivariate analysis.

Depressive disorder in children and adolescents.

Depression is a relatively common health issue in children and adolescents. Different pathogenetic factors are implied: genetic, biological, psychological and environmental. The core symptoms of depression are the same for children, adolescents and adults but the prominence of characteristic symptoms changes with age. The clinical picture of depression according to age level is described in different types of mood disorders (major depressive disorder, dysthymia, bipolar disorder) and in mental retardation. Over half of the youths with depression have comorbid conditions: anxiety disorders, other mood disorders, attention deficit/hyperactivity disorder, and conduct disorders. Different factors affect the natural course and risk of suicide. Assessment procedures of depression and comorbid conditions include a psychiatric evaluation of the depressed subject and his family, structured interviews and specific rating scales. A comprehensive treatment strategy, psychoeducational, psychotherapeutic and psychopharmacological, is proposed.

Reboxetine: a review of antidepressant tolerability.

The tolerability of reboxetine was evaluated in 2613 adult (aged 18-65 years) or elderly (aged > 65 years) patients with depressive illness treated with reboxetine, comparator agents or placebo, who entered both short- and long-term, controlled and uncontrolled clinical trials. The reboxetine adverse-event profile in acute depression was established by comparison with placebo in 746 patients. Overall, 69% of 373 patients treated with reboxetine experienced adverse events compared with 57% of 373 patients in the placebo group. The majority of adverse events were moderate in severity, and discontinuation because of adverse events was low and comparable in both the reboxetine (8%) and the placebo (7.5%) group. When compared with imipramine, reboxetine was better tolerated. Most side-effects were less common in the reboxetine than the imipramine cohort, and fewer patients receiving reboxetine (10% in adult patients; 11% in elderly patients) discontinued treatment because of adverse events than those receiving imipramine (14% in adult patients; 16% in elderly patients). Compared with fluoxetine, the total frequency of adverse events was similar in reboxetine-treated patients (67%) and fluoxetine-treated patients (65%). In the fluoxetine group, 7% discontinued because of adverse events compared to 12% in the reboxetine group and 12% in the corresponding placebo group. In a 12-month placebo-controlled study, discontinuation because of adverse events in both groups was low (reboxetine 4%; placebo 1%), and the total frequency of adverse events was only marginally higher with reboxetine (28%) than with placebo (23%). Overall, no consistent changes were found in laboratory tests or electrocardiogram recordings and there was no indication of withdrawal symptoms upon abrupt reboxetine discontinuation. Reboxetine, a novel selective noradrenaline reuptake inhibitor, is well tolerated by adults and the elderly during short- and long-term treatment for depression.

Degradation of complex carbohydrates by Bifidobacterium spp.

Two hundred and ninety strains of 29 species of bifidobacteria from human and animal origin were surveyed for their ability to ferment complex carbohydrates. The substrates fermented by the largest number of species were D-galactosamine, D-glucosamine, amylose and amylopectin. Many of the species isolated from animal habitats showed reduced fermentation activity. Bifidobacterium dentium strains fermented gum guar and gum locust bean; porcine gastric mucin was fermented only by B. bifidum, B. infantis was the only species to ferment D-glucuronic acid; strains of B. longum fermented arabinogalactan and the gums arabic, ghatti and tragacanth; alpha-L-fucose was fermented by strains of B. breve, B. infantis and B. pseudocatenulatum. A key to the differentiation of Bifidobacterium species of human origin is provided.

Prolactin levels in young children with pervasive developmental disorders during risperidone treatment.

Although hyperprolactinemia is a common side effect during risperidone treatment in adult patients, no information is available on young children. The aim of this study is to report on serum prolactin levels in 25 young autistic children (22 males and 3 females, age range 3.9-7 years, mean age 4.10 years) during treatment with risperidone (dosage range 0.25-0.90 mg/day, mean dosage 0.52 mg/day). Prolactin levels were measured at baseline and after 10 weeks of treatment. The clinical outcome measure used was the Clinical Global Impression-Improvement. Serum prolactin was 9.77 +/- 3.94 ng/mL at baseline and 25.92 +/- 13.9 ng/mL during the 10th week of treatment (p < 0.001). Six children (24%) showed prolactin levels lower than 15 ng/mL, which is the upper normal level; eight children (28%) had prolactin levels higher than two times the upper limit (30 ng/mL). Hyperprolactinemia did not show significant correlations with age, weight, or risperidone dosage. There was no relation with clinical outcome. Dose reduction of risperidone resulted in a decrease of prolactin levels. None of the children showed clinical signs of hyperprolactinemia. Given the paucity of available data on potential effects of long-term hyperprolactinemia, a monitoring of prolactin during treatment with risperidone and other typical and atypical antipsychotics may be warranted.

Paroxetine in child and adolescent outpatients with panic disorder.

Paroxetine has repeatedly been shown to be effective in the treatment of panic disorder (PD) in adults, and, according to previous case observations, it may be useful in treating children and adolescents with PD as well. This preliminary naturalistic study examines effectiveness and safety of paroxetine in the treatment of children and adolescents with PD. A chart review was conducted on 18 patients with Diagnostic and Statistical Manual of Mental Disorders PD admitted to the Division of Child Neurology and Psychiatry and to the Department of Psychiatry at the University of Pisa. Paroxetine was given at an initial mean dosage of 8.9 +/- 2.1 mg/day and was gradually increased up to 40 mg/day, depending on clinical response and side effects. Clinical status was assessed with the Clinical Global Impression (CGI) and adverse effects were assessed retrospectively at each visit. Patients with final CGI-Improvement scores of 1 or 2 were considered responders. Mean paroxetine treatment duration was 11.7 +/- 8.3 months, with a mean final dosage of 23.9 +/- 9.8 mg/day (range, 10-40 mg/day). No patient had to interrupt the treatment because of side effects. Fifteen patients (83.3%) were considered responders. The mean change on the CGI-Severity scale was statistically significant (p < 0.0001). Paroxetine was well tolerated and effective in the treatment of PD in these children and adolescents.

Risperidone monotherapy in preschool children with pervasive developmental disorders.

The aim of this preliminary study was to examine the short-term efficacy and safety of the atypical antipsychotic risperidone in preschool autistic children. The sample consisted of 10 subjects (7 males and 3 females) aged 3 9/12 to 6 6/12 years (mean age 4.7 years). A 16-week open-label trial with risperidone monotherapy was initiated at a starting dose of 0.25 mg daily and was increased to a maximum dose of 0.50 mg (0.027 mg/kg daily). Outcome measures were the Childhood Autism Rating Scale, the Children's Psychiatric Rating Scale, Clinical Global Impression (improvement score), and the Children's Global Assessment of Functioning. Two subjects did not complete the trial because of side effects (tachycardia and flushes, fever and hyporexia). After the 16-week treatment, data from the eight children who completed the trial indicated a modest improvement in the Childhood Autism Rating Scale total score, Children's Psychiatric Rating Scale total score, and Children's Global Assessment of Functioning. According to the Clinical Global Impression, the global improvement score for four subjects was much improved or very much improved; the score for the other four children was minimally improved. None of the children exhibited behavioral deterioration. The side effects in the eight children were not severe.

Effects of phenylalanine, histidine, and leucine on basal and GHRH-stimulated GH secretion and on PRL, insulin, and glucose levels in short children. Comparison with the effects of arginine.

Of the amino acids arginine is the most potent GH secretagogue in man. It potentiates the GH response to GHRH, exerts a weaker PRL-releasing effect, stimulates insulin and glucagon and induces a biphasic glucose variation. The potency and effects of other amino acids on pituitary and pancreatic hormones need to be clarified. In 43 children with normal short stature (5.3-14.0 yr; 30 M and 13 F) the effects of the infusion of phenylalanine (Phe, 0.08 g/kg), histidine (His, 0.1 g/kg), and leucine (Leu, 0.08 g/kg) on basal and GHRH-stimulated GH secretion and on PRL, insulin and glucose levels were studied and compared with those of arginine at high (hArg, 0.5 g/kg) or low dose (lArg, 0.2 g/kg). Phe increased basal (p < 0.05) but not GHRH-stimulated GH levels, induced PRL and insulin rises (p < 0.03 and p < 0.03), and did not change glycemia. Though a trend toward an increase in basal GH levels was found after His, His and Leu did not significantly modify either basal or GHRH-induced GH secretion nor basal PRL, insulin and glucose levels. Both hArg and lArg increased basal (p < 0.0001 and p < 0.05, respectively) and GHRH-stimulated GH levels (p < 0.006 and p < 0.006). hArg increased both PRL (p < 0.002) and insulin levels (p < 0.005) more (p < 0.0005 and p < 0.004) than lArg (p < 0.005 and p < 0.005), while glucose levels showed a similar increase followed by a similar decrease. We conclude that in childhood: a) Phe significantly increases GH secretion but, differently from Arg, does not potentiate the response to GHRH, suggesting different mechanisms of action of these amino acids; b) differently from His and Leu, Phe is a PRL and insulin secretagogue but is less potent than Arg; c) Arg has the highest stimulatory effect on pituitary and pancreatic hormones.

Generalized anxiety disorder in adolescents and young adults with mild mental retardation.

This report examines clinical features of generalized anxiety disorder in adolescents and young adults with mild mental retardation (MR), compared with children and adolescents with normal IQ. Frequency of symptoms, comorbidity, agreement between reports of subjects and parents, correlation between IQ and severity of disorder, and comparison between frequency of symptoms in the experimental and control groups are described. Twenty-two subjects with MR (12 males and 10 females aged 11-25 years; mean age = 16.3), 30 children (19 males and 11 females aged 7-11.11; mean age = 10), and 30 adolescents (18 males and 12 females aged 12.1-18; mean age = 15.2) participated in the study. All the subjects were comprehensively diagnosed with diagnostic interviews (K-SADS or DICA-R). According to our data, generalized anxiety disorder can be diagnosed in adolescents with mild MR, with high agreement between self-reports and parent reports. Phenomenology of GAD in mildly developmentally delayed persons grossly paralleled that of normal IQ people, except for brooding, somatic complaints, and sleep disorders. Number and severity of symptoms did not correlate with Full Scale and Verbal IQs. High rates of comorbidity with depression were evident both in normal IQ and in developmentally delayed subjects.