Second-line chemotherapy and new drugs for ovarian carcinoma

Epithelial ovarian carcinoma represents a prototypic example of neoplastic disease sharing at the same time good chemosensitivity as well as marked propensity to relapse. If in one hand the definition of almost clear-cut guidelines has been reached in the setting of first-line therapy (i.e., cytoreductive surgery followed by first-line chemotherapy), more difficult to discern for the oncologist remains the choice of treatment in the occasion(s) of relapse(s). This article focuses on this particular setting of disease, analyzing the specific criteria of choice of drug or their combinations; the definite criteria followed for the use of platinum compounds in the second line of treatment, even if already utilized in the front line therapy, are also analyzed. Specific attention has also been paid in the definition of the role of single parameter as a "prognosticator" and/or as "predictor" of response. The Authors emphasize how clinical definitions remain the more reliable, simple, reproducible tools in therapeutical decision making.     

Disease-Specific Quality of Life in Young Patients With Tourette Syndrome

Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and is often associated with comorbid behavioral problems. Research with generic instruments in child populations showed that comorbid disorders can have a greater impact on health-related quality of life than tic severity. This study investigated the usefulness of a newly developed disease-specific instrument, the Gilles de la Tourette Syndrome–Quality of Life Scale for Children and Adolescents (GTS-QOL-C&A), in assessing health-related quality of life in young patients with Tourette syndrome with and without behavioral comorbidity. We recruited 75 patients with Tourette syndrome (60 males; age 12.4 ± 3.2 years). All participants were evaluated by a neuropsychiatrist and completed a standardized psychometric battery, including the GTS-QOL-C&A, Child Depression Inventory, and Multidimensional Anxiety Scale for Children. Forty-two patients (56%) fulfilled diagnostic criteria for at least one comorbidity: obsessive-compulsive disorder (n = 25 patients [33.3%]); attention deficit/hyperactivity disorder (n = 6 patients [8%]); both (n = 11 patients [14.7%]). The GTS-QOL-C&A demonstrated usefulness in differentiating “pure” Tourette syndrome from Tourette syndrome “plus” behavioral problems with regard to health-related quality of life scores for the obsessive-compulsive subscale. In addition to focusing on core tic symptoms, the GTS-QOL-C&A showed sensitivity to the impact of behavioral comorbidities on health-related quality of life and can usefully complement existing nonspecific instruments.     

Modelling the Spatial and Temporal Dynamics of Paralytic Shellfish Toxins (PST) at Different Scales: Implications for Research and Management

Harmful algal blooms, in particular recurrent blooms of the dinoflagellate Alexandrium catenella, associated with paralytic shellfish poisoning (PSP), frequently limit commercial shellfish harvests, resulting in serious socio-economic consequences. Although the PSP-inducing species that threaten the most vulnerable commercial species of shellfish are very patchy and spatially heterogeneous in their distribution, the spatial and temporal scales of their effects have largely been ignored in monitoring programs and by researchers. In this study, we examined the spatial and temporal dynamics of PSP toxicity in the clam (Ameghinomya antiqua) in two fishing grounds in southern Chile (Ovalada Island and Low Bay). During the summer of 2009, both were affected by an intense toxic bloom of A. catenella (up to 1.1 × 10⁶ cells L⁻¹). Generalized linear models were used to assess the potential influence of different environmental variables on the field detoxification rates of PSP toxins over a period of 12 months. This was achieved using a four parameter exponential decay model to fit and compare field detoxification rates per sampling site. The results show differences in the spatial variability and temporal dynamics of PSP toxicity, given that greater toxicities (+10-fold) and faster detoxification (20% faster) are observed at the Ovalada Island site, the less oceanic zone, and where higher amounts of clam are annually produced. Our observations support the relevance of considering different spatial and temporal scales to obtain more accurate assessments of PSP accumulation and detoxification dynamics and to improve the efficacy of fisheries management after toxic events.     

Beitrag zur wachstumserregenden und wachstumsfördernden Wirkung von Nekrohormonen aus Kulturen normaler und neoplastischer Gewebe

Ohne Zusammenfassung     

Effects of intrathecal nocistatin on the flexor reflex and its interaction with orphanin FQ nociceptin

We studied the effects of intrathecal (i.t.) nocistatin, a peptide identified from the precursor of orphanin FQ/nociceptin (OFQ) on the spinal nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats and its interaction with i.t. OFQ. Nocistatin induced a moderate, non-dose-dependent facilitation of the flexor reflex without producing reflex depression whereas i.t. OFQ induced a biphasic dose-dependent facilitatory and inhibitory effect. The facilitatory effect of low dose (0.55 pmol) OFQ was significantly increased by nocistatin. On the other hand, the duration, but not magnitude, of reflex depression induced by a high (550 pmol) dose of OFQ was significantly shortened by 5.5 nmol nocistatin. Thus, nocistatin interacts with OFQ in a complex fashion, increasing excitation and reducing inhibition. No evidence was obtained for an antinociceptive effect of nocistatin in rat spinal cord.     

Endogenous nociceptin signaling and stress-induced analgesia

Nociceptin/orphanin FQ (NC) and its receptor (OP4) have been implicated in pain transmission. The aim of the present study was to investigate the role of the NC/OP4 system in stress-induced analgesia (SIA). The tail-withdrawal assay was performed in mice stressed by forced swimming in water at 15 degrees C (high severity swims) or 32 degrees C (low severity swims). High severity swims produced a naloxone-insensitive antinociceptive effect which was blocked by supraspinal NC (1 nmol). The selective OP4 receptor antagonist, [Nphe1]NC(-13)NH2 (30 nmol), was inactive by itself, but prevented the effect of NC. Low severity swims produced a milder analgesic effect that was partially antagonized by naloxone, completely blocked by NC and potentiated by [Nphe1]NC(-13)NH2. These findings confirm the anti-analgesic role of supraspinal NC and suggest that endogenous NC signaling counteracts the opioid component of SIA.     

Evaluation of etiologic and prognostic factors in neonatal convulsions

This study evaluated etiologic and risk factors affecting long-term prognoses of neurologic outcomes in newborns with neonatal seizures. We enrolled patients at chronologic ages of 23-44 months, referred to the Department of Pediatric Neurology, Istanbul Medical Faculty, from January 1, 2007-December 31, 2009, after manifesting seizures in their first postnatal 28 days. Of 112 newborns, 41 were female, 71 were male, 33 were preterm, and 79 were full-term. Perinatal asphyxia (28.6%) and intracranial hemorrhage (17%) were the most common causes of neonatal seizures. Cerebral palsy developed in 27.6% of patients during follow-up. The incidence of epilepsy was 35.7%. Almost 50% of patients manifested developmental delay in one or more areas. Global developmental delay was the most common (50.8%) neurologic disorder. The correlation between gestational age or birth weight and adverse outcomes was nonsignificant. Etiology, Apgar score, need for resuscitation at birth, background electroencephalogram, neonatal status epilepticus, cranial imaging findings, type/duration of antiepileptic treatment, and response to acute treatment were all strong prognostic factors in neurologic outcomes. Neonatal seizures pose a threat of neurologic sequelae for preterm and full-term infants. Although the number of recognized etiologic factors in neonatal seizures has increased because of improvements in neonatology and diagnostic methods, perinatal asphyxia remains the most common factor.