Effectiveness of a low support, remotely accessible, cognitive remediation training programme for chronic psychosis: cognitive, functional and cortical outcomes from a single blind randomised controlled trial.

BACKGROUND: Cognitive remediation (CR) training has emerged as a promising approach to improving cognitive deficits in schizophrenia and related psychosis. The limited availability of psychological services for psychosis is a major barrier to accessing this intervention however. This study investigated the effectiveness of a low support, remotely accessible, computerised working memory (WM) training programme in patients with psychosis. METHODS: Ninety patients were enrolled into a single blind randomised controlled trial of CR. Effectiveness of the intervention was assessed in terms of neuropsychological performance, social and occupational function, and functional MRI 2 weeks post-intervention, with neuropsychological and social function again assessed 3-6 months post-treatment. RESULTS: Patients who completed the intervention showed significant gains in both neuropsychological function (measured using both untrained WM and episodic task performance, and a measure of performance IQ), and social function at both 2-week follow-up and 3-6-month follow-up timepoints. Furthermore, patients who completed MRI scanning showed improved resting state functional connectivity relative to patients in the placebo condition. CONCLUSIONS: CR training has already been shown to improve cognitive and social function in patient with psychosis. This study demonstrates that, at least for some chronic but stable outpatients, a low support treatment was associated with gains that were comparable with those reported for CR delivered entirely on a 1:1 basis. We conclude that CR has potential to be delivered even in services in which psychological supports for patients with psychosis are limited.

Successful pregnancy and breastfeeding in a woman with mucopolysaccharidosis type I while receiving laronidase enzyme replacement. therapy.

The authors describe the first mother-infant pair to complete an on-going, prospective, open-label, Phase 4 trial (ALIU) UU3, NCT00418821) determining the safety of laronidase enzyme replacement therapy (ERT) in pregnant women with mucopolysaccharidosis type I (MPS I) and their breastfed infants. The mother, a 32-year-old with attenuated MPS I (Scheie syndrome), received laronidase for three years and continued treatment throughout her second pregnancy and while lactating. A healthy 2.5 kg male was delivered by elective cesarean section at 37 weeks. He was breastfed for three months. No laronidase was detected in breast milk. The infant never developed anti-laronidase IgM antibodies, never had inhibitory antibody activity in a cellular uptake assay, and always had normal urinary glycosaminoglycan (GAG) levels. No drug-related adverse events were reported. At 2.5 years of age, the boy is healthy with normal growth and development. In this first prospectively monitored mother-infant pair, laronidase during pregnancy and breastfeeding was uneventful.

Computerised working-memory focused cognitive remediation therapy for psychosis--A preliminary study.

BACKGROUND: Cognitive deficits are a core feature of schizophrenia and related psychotic disorders and are associated with decreased levels of functioning. Behavioural interventions have shown success in remediating these deficits; determining how best to maximise this benefit while minimising the cost is an important next step in optimising this intervention for clinical use. AIMS: To examine the effects of a novel working-memory focused cognitive remediation (CR) training on cognitive difficulties based on internet delivery of training and weekly telephone support. METHOD: Participants with a diagnosis of psychosis (n=56) underwent either 8 weeks of CR (approximately 20 h) or 8 weeks of treatment as usual (TAU). General cognitive ability, working memory and episodic memory were measured both pre and post intervention for all participants. RESULTS: In addition to improvements on trained working memory tasks, CR training was associated with significant improvements in two tests of verbal episodic memory. No association between CR and changes in general cognitive ability was observed. Effect sizes for statistically significant changes in memory were comparable to those reported in the literature based primarily on 1:1 training. CONCLUSIONS: The cognitive benefits observed in this non-randomised preliminary study indicate that internet-based working memory training can be an effective cognitive remediation therapy. The successes and challenges of an internet-based treatment are discussed.

Neuropsychiatric effects and type of IFN-alpha in chronic hepatitis C.

Chronic hepatitis is often associated with neuropsychiatric disorders. Interferon (IFN) is the drug most widely used to treat this disease, and its side effects, such as depression, often involve the central nervous system (CNS). Symptoms include a slowing down of psychomotor functions, loss of interest, frontal lobe dysfunction, parkinsonism, and delirium. The occurrence of these complications calls for dropping out of IFN treatment or for a significant dose reduction and administration of antidepressants. Efficacy and side effects vary on the basis of the IFN type employed. The aim of our study was to evaluate if the frequency, form, and degree of depression induced are related to the type of IFN employed. We studied 96 patients with chronic hepatitis C. Our study series was divided into four groups according to the type of IFN-alpha administered. Depression degree was clinically evaluated using the Hamilton Depression Rating Scale (HAM-D). All patients were tested before treatment and 1, 3, and 6 months (15 days after the end of treatment) later. Our results showed that the type of IFN used seemed to influence the depression onset rate, with the leukocyte type inducing the lowest level of depression. However, when a number of symptoms associated with the depression were considered, the results of other types of IFN-alpha were found to be better. Use of the most suitable type of IFN-alpha could thus lead to more personalized treatment, with fewer side effects. The type of IFN used seems to influence the psychological side effects and the adaptation rate to therapy. It would be appropriate to choose the type of IFN on the basis of a neuropsychiatric assessment carried out before treatment.

A cluster analysis study of acetyl-L-carnitine effect on NMDA receptors in aging.

Aging is associated with a reduction in the maximum density of n-methyl-d-aspartate (NMDA)-sensitive glutamate binding sites in the hippocampus of Fischer 344 rats. This study was designed to investigate the effect of acetyl-l-carnitine (ALCAR) on NMDA receptors in the old rat (24 months) after chronic or single-dose treatments. The number of NMDA receptors was significantly decreased in the old rat hippocampus by 19.5% compared with the young rat. A six-month treatment with ALCAR in the old rat attenuated the loss of NMDA binding sites in the hippocampus. A single-dose treatment with ALCAR in the old rat increased the Bmax value by 35%, while no change was observed in the young group. We conclude that ALCAR can exert two actions: a trophic/neuro-preserving one when chronically administered during aging, and a stimulatory one when given at a single dose in the aged rat.

Potent integrin antagonists from a small library of RGD-including cyclic pseudopeptides.

[structure: see text]. A small library of cyclic RGD pseudopentapeptides incorporating stereoisomeric 6,5- and 7,5-fused bicyclic lactams was synthesized with the aim of developing active and selective integrin antagonists. The solid-phase synthesis and activity of these RGD derivatives is described. The approach led to two of the most active known inhibitors of alpha(V)beta3 receptor.

MPTP and convulsive responses in rodents.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg s.c. for 5 days) to mice resulted in complete abolishment of strychnine seizure and of the tonic phase of the maximal electroshock response. Bicuculline and picrotoxin convulsions were not significantly affected by MPTP treatment. The severity of the pentylenetetrazole seizures was mildly, but significantly affected in the protective way. MPTP depleted neostriatal dopamine and its metabolites, together with hippocampal norepinephrine. No nigral neuronal loss was detected histologically. Strychnine seizures and the tonic phase of the maximal electroshock response are thought to depend mostly on hindbrain (bulbo-spinal) structures. Thus, these experiments suggest that a caudally projecting system originates from the substantia nigra, pars compacta, and/or locus coeruleus, controlling seizures that involve bulbo-spinal centers. While neostriatal dopamine depletion offers a good index of seizure resistance, its role in the protection from seizures remains to be established.

Behavioral and neurochemical effects of dopaminergic drugs in models of brain injury.

The dopaminergic drugs, ropinirole and dihydroergocryptine (DHECP) were injected subcutaneously (s.c.) at doses of 0.5 and 1 mg/kg/day for 7 days into male rats of the Sprague-Dawley strain. The drug pretreatment reverted amnesia induced in rats by hypobaric hypopxia and tested in active and passive avoidance tasks. Furthermore, a partial restoration of memory retention was found in animals with a 2-month brain occlusive ischemia induced by manipulation of the four major arteries of the brain. No major changes were found in spontaneous motor activity, but drug treatment increased ambulation of animals subjected to acute or chronic experimental manipulation. In a model of kainate-induced epilepsy, ropinirole or DHECP did not affect seizure parameters, but reduced mortality rate. At the end of behavioral procedures, in all animals subjected to hypobaric hypoxia or to brain occlusive ischemia glutathione redox index (glutathione reduced/glutathione oxidized ratio) was measured in the frontal cortex, striatum and hippocampus. It was found that experimental models of brain injury were followed by a decrease of reduced glutathione content in all brain areas. The glutathione redox index was augmented by ropinirole or DHECP treatment in all brain areas. These behavioral and neurochemical findings suggest that ropinirole and DHECP may exert either protective activity (as found in animals pretreated with these drugs and exposed to hypobaric hypoxia) or reversal of brain injury (as found in animals treated after two-month occlusive brain ischemia). Thus, both drugs may be studied as therapeutic agents in brain injuries of various origin.

Acetyl-L-carnitine affects aged brain receptorial system in rodents.

Acetyl-L-carnitine (ALCAR), the acetyl ester of carnitine, is regarded as a compound of considerable interest because of its capacity to counteract several physiological and pathological modifications typical of brain ageing processes. In particular, it has been demonstrated that ALCAR can counteract the age-dependent reduction of several receptors in the central nervous system of rodents, such as the NMDA receptorial system, the Nerve Growth Factor (NGF) receptors, those of glucocorticoids, neurotransmitters and others, thereby enhancing the efficiency of synaptic transmission, which is considerably slowed down by ageing. The present review thus postulates the importance of ALCAR administration in preserving and/or facilitating the functionality of carnitines, the concentrations of which are diminished in the brain of old animals.

Comparative bioavailability of a new formulation of fluoxetine drops.

Fluoxetine drops and marketed fluoxetine capsules had quite the same Cmax (50.25 +/- 4.43 vs 47.55 +/- 5.29 ng/ml), but significantly different AUC0-t (717.27 +/- 71.29 vs 644.91 +/- 78.91 ng/ml/h). Furthermore the drops were characterised by a very early Tmax (4.61 +/- 0.85 hours) with a highly significant difference in comparison to the capsules reference compound (6.72 +/- 1.23 hours). After log transformation 90% C.I. for Cmax, AUC 0-t and AUC0-. were 1.05, 1.11, 0.82 respectively. The two products, therefore, cannot be considered bioequivalent. Our results demonstrate that fluoxetine drops and capsules significantly differ for their pharmacokinetics, with an earlier Tmax and a higher AUC0-t after the administration of the drops preparation.

[Potential cost reductions for the National Health Service through a telecardiology service dedicated to general practice physicians]. / Riduzione potenziale dei costi per il Servizio Sanitario Nazionale mediante un servizio di telecardiologia dedicato ai medici di medicina generale.

BACKGROUND: Rising health care costs resulted in increasing pressure on the health care system and stimulated new strategies for improving the efficiency of care. A telecardiology service provides a useful support to general practitioners in the management of cardiac patients and contributes to the optimization of health care costs in terms of appropriateness of hospital admission and diagnostic testing. The aim of our study was to evaluate the reduction in the number of referrals to the Emergency Department and to cardiological evaluation resulting from the employment of a telecardiology service by general practitioners. METHODS: Eight hundred and ninety-one consecutive calls arrived to the receiving station of the telecardiology service were analyzed. One hundred and fifty general practitioners received a portable electrocardiographer (Card-Guard 7100, Rehovot, Israel) transferring, by a mobile or fixed telephone, a 12-lead ECG to a receiving station, where a cardiologist was available for reporting and for interactive teleconsultation. At the onset of the phone call, a question was asked to the general practitioner: "What would you have done without the telecardiology service?". The possible answers were: "No actions"; "Referral to the Emergency Department"; "Cardiological consultancy"; "Further investigations". Then we collected the history, risk factors, symptoms and therapy of the patients; the general practitioner sent the ECG tracing by phone. RESULTS: Eight hundred and ninety-one patients were enrolled (402 males, 489 females, mean age 59 +/- 19 years); 465 (52%) patients were symptomatic; 36.4% had no evidence of previous cardiac disease, 35.1% had systemic hypertension, 10.6% had ischemic cardiac disease, 3.7% had atrial fibrillation, and 11.9% other diseases. ECG was normal in 55%. The general practitioners would have sent to the Emergency Department 106 patients (11.9%), and requested further investigations in 717 patients (80.5%). The cardiologist of the telecardiology service solved the problems of the general practitioners in 657 cases (73.7%), sent 56 patients (6.3%) to the Emergency Department, and asked for further investigations in 178 patients (20%), with a reduction of 47% of Emergency Department admission (p < 0.001) and of 95% of further investigations (p < 0.0001) respectively. The cost analysis showed a reduction, between the two modalities, varying from Itl 22,760,000 and Itl 140,060,000 for 891 calls. CONCLUSIONS: Telemedicine is a useful tool for the support of general practitioners' daily activity, with a possible cost reduction due to increased appropriateness of hospital admission and of diagnostic testing.

[Acute psychosis and vigabatrin in childhood]. / Psicosi acuta e vigabatrin in età pediatrica.

Vigabatrin is an irreversible inhibitor of gamma-aminobutyrate (Gaba) aminotransferase, producing an increase in Gaba concentrations in the brain. It may prove to be an important drug in the treatment of refractory epilepsy, but would be payed attention to behavioural changes noted in association with vigabatrin treatment. Behaviour disturbances, as psychosis, associated to vigabatrin are ben described in adult patients, while are uncommon in childhood. We report a case of acute psychosis occurred in a child in treatment with vigabatrin.

[Congenital dysplasia of the hip. Preliminary results of a longitudinal study in the first 6 months of life]. / La displasia congenita dell'anca (DCA). Risultati preliminari di uno studio longitudinale nei primi 6 mesi di vita.

The authors report their experience of a serial follow-up for congenital dysplasia of the hip (CDH). 699 babies born during a three-months period were examined on their first day of life, on the forth and at the age of 1 and 6 months. 2 dislocated hips, 222 clicking hips were discovered in the neonatal period. At the first month 1 dislocated hip and only 6 clicking hips were detected. At the sixth month all babies were normal with the exception of two clicking hips. X-ray examination confirmed clinical dislocation diagnosis and showed pathological signs (subluxation and acetabular dysplasia) also in normal and clicking hips. According to their results the authors suggest that clinical examination during the first 6 months of life and X-ray can decrease the incidence of late diagnosis of CDH.

[Intracranial hemorrhage in Schoenlein-Henoch syndrome]. / Emorragia endocranica nella sindrome di Schoenlein-Henoch.

Henoch-Schoenlein syndrome (HSS) is one of the most common vasculitis in childhood. It is characterized by non-thrombocytopenic purpura, arthritis, abdominal pain, and sometimes intestinal haemorrhage and renal involvement. It may be complicated by haemorrhages in uncommon sites, such as lungs, testicles, bladder, and central nervous system. Neurological involvement in HSS is often underestimated, usually occurring with headache, irritability, and behavioural alterations, whereas endocranial haemorrhage is quite rare. We report a case of endocranial haemorrhage in a child with HSS.

[Clinical-instrumental dissociation in a case of Reye's syndrome]. / Dissociazione clinico-strumentale in un caso di sindrome di Reye.

We report the case of a boy 5 years old we admitted to our PICU with signs of impending hepatic failure (hypertransaminasemia, hyperammonemia, prolonged PT) following mild upper respiratory infection and irrepressible vomiting. We observed no neurological abnormalities excepting slight lethargy; on the contrary, EEG findings showed severe diffuse slowing and high-voltage Delta activity. Our diagnosis of Reye's syndrome was later confirmed by liver biopsy. Clinical and electrophysiological signs recovered after 48-72 hours and no explication was found for this anomalous Reye's syndrome presentation. Further studies are needed for understanding the basis of neurological involvement of stage I Reye's syndrome.

[Parity and the quantity of suckled maternal milk produced in the 1st 4 days of the puerperium]. / Parità e quantità di latte materno da suzione prodotta nei primi quattro giorni del puerperio.

In 120 nursing mothers, the quantity of milk suckled was evaluated during the first days of the puerperium. Measurements of the milk intake were based on the difference between the weights of the neonate before and after each feeding. It was noted that, as the parity of the mother increased, the mean quantity of breast milk suckled/24 hours increased on the 1st, 2nd and 3rd day of the puerperium, as well as during the last 24 hours prior to discharge from the hospital (3rd or 4th post-partum day). Given the importance of a satisfactory flow of breast milk during the first days of the puerperium in the successful initiation of the breast-feeding experience, the authors would like to emphasize the increased risk of failure in the primipara and to suggest that greater attention be given to the effect of maternal parity in programs which promote breast-feeding.

[Type of diet and "ambulatory" pathology in the first 6 months of life]. / Tipo di alimentazione e patologia "ambulatoriale" nei primi sei mesi di vita.

This work is a contribution to the investigation that mainly in the last year have been widely performed to evaluate the protecting action of breast feeding against some typical pathological occurrences in the first months of life. Authors studied, for six months, 117 babies. The respiratory and intestinal illness have been found (in progress or anamnestically) during pediatric monthly or occasionally visits. 33% of the babies were fed with milk formula since the first life months; the remainder 67% were breastfed during one month at least. By statistic correlation of type of feeding and disease frequency, there is evidence of the following: 1) Babies, breastfed during 6 months, have lower frequency of respiratory pathology, when compared (p 0.05) with 6 months bottle fed ones. 2) Babies, breastfed during 2 months have lower frequency of intestinal pathology when compared (p 0.05) with bottle fed ones. Therefore, it seems that the most interesting results coming out from this study is that the protective action of breast feeding concerns not only the intestinal disease, but the respiratory ones too, when, however, the breast feeding period is enough extended.

Age-dependent loss of NMDA receptors in hippocampus, striatum, and frontal cortex of the rat: prevention by acetyl-L-carnitine.

Acute i.p. administration of Acetyl-L-Carnitine (ALCAR), a component of several biological systems, has been found to modify spontaneous and evoked electrocortical activity in young rats, and, in the old rats, to improve learning ability and to increase the number of NMDA receptors in the whole brain. The present study was aimed at ascertaining the effect of chronic treatment with ALCAR added to drinking water on age-related changes in the different brain areas of rats. In twenty-four-month-old rats, ALCAR treatment for six months significantly impeded the decline in the number of NMDA receptors within the hippocampus, the frontal cortex and the striatum compared to the adult animal. This finding thus confirms the previously reported positive effect of ALCAR on the brain NMDA receptor system.

Risk factors for atherogenesis in children with spina bifida.

INTRODUCTION: Several literature reports have demonstrated that cardiovascular disease is one of the most frequent pathologies in patients with spinal cord injury. AIM: The aim of this study is to reveal changes in the lipid profile in non-obese children with spina bifida/myelomeningocele (MMC). DISCUSSION: The original results demonstrate the necessity of metabolic surveillance in these patients. Daily physical activity must be ensured early on frequency in non-able-bodied children in order to prevent changes in seric lipoproteins.

Acute hydrocephalus as a consequence of mumps meningoencephalitis.

Aqueductal stenosis can result from mumps meningoencephalitis. We report a case of acute hydrocephalus from an aqueductal stenosis developed immediately after a clinically evident mumps infection. The patient, aged two years, was treated with an antiedema therapy, and a ventriculoperitoneal shunt was placed. His clinical conditions rapidly improved. Only mumps virus was found in his cerebrospinal fluid culture. This case probably represents the earliest hydrocephalus from mumps, among those reported in the literature.