IGF1 as a Potential Treatment for Rett Syndrome: Safety Assessment in Six Rett Patients.

Rett syndrome (RTT) is a devastating neurodevelopmental disorder that affects one in ten thousand girls and has no cure. The majority of RTT patients display mutations in the gene that codes for the methyl-CpG-binding protein 2 (MeCP2). Clinical observations and neurobiological analysis of mouse models suggest that defects in the expression of MeCP2 protein compromise the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function, such as insulin-like growth factor 1 (IGF1), are good candidates for ameliorating the symptoms of RTT. IGF1 and its active peptide, (1-3) IGF1, cross the blood brain barrier, and (1-3) IGF1 ameliorates the symptoms of RTT in a mouse model of the disease; therefore they are ideal treatments for neurodevelopmental disorders, including RTT. We performed a pilot study to establish whether there are major risks associated with IGF1 administration in RTT patients. Six young girls with classic RTT received IGF1 subcutaneous injections twice a day for six months, and they were regularly monitored by their primary care physicians and by the unit for RTT in Versilia Hospital (Italy). This study shows that there are no risks associated with IGF1 administration.

Variant of Rett syndrome and CDKL5 gene: clinical and autonomic description of 10 cases.

UNLABELLED: Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively females. The Hanefeld variant, or early-onset seizure variant, has been associated with mutations in CDKL5 gene. AIMS: In recent years more than 60 patients with mutations in the CDKL5 gene have been described in the literature, but the cardiorespiratory phenotype has not been reported. Our aim is to describe clinical and autonomic features of these girls. METHODS: 10 girls with CDKL5 mutations and a diagnosis of Hanefeld variant have been evaluated on axiological and clinical aspects. In all subjects an evaluation of the autonomic system was performed using the Neuroscope. RESULTS: Common features were gaze avoidance, repetitive head movements and hand stereotypies. The autonomic evaluation disclosed eight cases with the Forceful breather cardiorespiratory phenotype and two cases with the Apneustic breather phenotype. CONCLUSIONS: The clinical picture remains within the RTT spectrum but some symptoms are more pronounced in addition to the very early onset of seizures. The cardiorespiratory phenotype was dominated by Forceful breathers, while Feeble breathers were not found, differently from the general Rett population, suggesting a specific behavioral and cardiorespiratory phenotype of the RTT the Hanefeld variant.

A comparison of proximal and distal radial nerve motor responses in axillary block using triple stimulation.

BACKGROUND AND OBJECTIVES: Stimulation of the radial nerve at the axilla may cause either a proximal movement (forearm extension) or distal movements (supination, wrist or finger extension). In the most recent studies on axillary block, only a distal twitch was accepted as valid. However, this approach was based only on clinical experience. The aim of this study was to verify if a proximal motor response can be considered a satisfactory endpoint. METHODS: This was a prospective, randomized, double-blinded study. One hundred fifty patients received a triple-injection axillary brachial plexus block in which the radial nerve was located by a proximal (group PROX) or a distal motor response (group DIST). Patients were assessed for sensory and motor block of the branches of the radial nerve by a blinded investigator at 5-minute intervals over 30 minutes. RESULTS: An 81% success rate for anesthetizing the sensory distal branches of the radial nerve was seen in group PROX; a significantly higher success rate was recorded in group DIST (95%). The onset time of sensory block for the distal branches of the radial nerve was significantly shorter in group DIST (9.9 +/- 6 v 15.4 +/- 7 minutes). The time to perform the block was slightly shorter and the localization of the nerve simpler in group PROX. The overall block success rate was not significantly different in the 2 groups. CONCLUSIONS: Local anesthetic injection at the proximal radial twitch significantly reduces the efficacy and prolongs the onset time of the radial nerve block. Searching for distal response is significantly more difficult and time consuming than searching for proximal response. However, it does not significantly increase patient discomfort or adverse effects.

Systemic chemotherapy in elderly patients with locally advanced and/or inoperable squamous cell carcinoma of the head and neck: impact of anemia and role of recombinant human erythropoietin.

A review of the incidence and management of anemia in elderly patients with head and neck carcinoma treated with systemic chemotherapy. The role of recombinant human erythropoietin in preventing or correcting chemotherapy-related anemia has been focused. Data concerning the prospective use of recombinant human erythropoietin (rhEpo) in a series of unfit elderly patients (EPs) treated with carboplatin plus 5-fluorouracil. Patients were randomly assigned to receive subcutaneous rhEpo 10,000U three times per week (TIW) (23 elderly patients) or no treatment (22 control patients). Recombinant hEpo was able to prevent anemia and to reduce transfusional requirements in treated patients as compared to untreated controls with a statistically significant difference. rhEpo also caused a positive effect on quality of life (QoL) parameters.

Escalating doses of paclitaxel and epirubicin in combination with cisplatin in advanced ovarian epithelial carcinoma: a phase I-II study.

Our objective was to identify a new active three-drug combination regimen consisting of paclitaxel (PTX), epirubicin (EPI) and cisplatin as first-line line chemotherapy for advanced ovarian carcinoma. A phase I study was carried out to evaluate the dose-limiting toxicity (DLT) and the maximally tolerated dose (MTD) of PXT and EPI in combination with a fixed dose of cisplatin every 4 weeks. Side-effects were recorded according to the NCI Common Toxicity Criteria. Patients were treated in cohorts of three with fixed-dose cisplatin 80 mg/m2 and EPI 80-->100 mg/m2 and PXT 100-->160 mg/m2 until DLT was reached. Once MTD was identified, a single-step phase II study was therefore carried out to test the clinical activity and panel of toxicity of such regimen. Objective responses were recorded according to the WHO criteria. Time to progression and overall survival (OS) were secondary endpoints. The DLT was myelosuppression and, in more detail, febrile neutropenia, which occurred at the fifth dose level (PTX 140 mg/m2, EPI 100 mg/m2 and cisplatin 80 mg/m2) in two out of three patients. Other side-effects were grade 3 mucositis in two out of three patients and grade 3 anemia in one case. The combination of cisplatin 80 mg/m2 plus EPI 80 mg/m2 and PCT 140 mg/m2 every 4 weeks was considered as the MTD. In the phase II study a complete response was observed in six patients (33%) and a partial response in nine cases (50%) for an overall response rate of 83% [95% confidence limits (CL) 59-96%]. Median time to progression of patients with measurable disease was 16.4 months. Median OS was not reached after a follow-up of 42 months. This study demonstrated that PTX and EPI can be safely administered in combination with cisplatin to fit patients with advanced epithelial ovarian carcinoma. The three-drug regimen of cisplatin 80 mg/m2, EPI 80 mg/m2 and PTX 140 mg/m2 every 4 weeks is very active, at least in terms of objective response rate. This level of activity overlaps with the 95% CL of the activity of cisplatin alone; however, it does encourage future trials of the combination.