Prenatal diagnosis and clinical outcome of ovarian cysts.

Technical refinements of ultrasound (US) have greatly affected the antenatal diagnosis and treatment of ovarian cysts. From 1985 to 1990 25 consecutive fetuses with ovarian cysts were followed-up by US both during pregnancy and postnatally. All cases were diagnosed between the 28th and 39th weeks of gestation. Deliveries were all at term; cesarean section was required only for obstetric complications. Eight fetuses (32%) showed US patterns of cyst torsion, a finding confirmed at surgery in all. In five patients US patterns suggested complications postnatally that were also confirmed at operation. In six cases cysts increased or remained unchanged in size after 15 days of life: in 50% of these surgery showed ovarian torsion. In the remaining six cases spontaneous resolution occurred within 1 to 4 months. One patient required intrauterine needle aspiration. There were two cases of intestinal obstruction. To date, more than 60% of newborns with ovarian cysts require oophorectomy; however, different treatments (cystectomy, needle aspiration, uncapping) combined with a close US follow-up are likely to reduce this percentage.     

Conventional vs controlled-release carbamazepine: a multicentre, double-blind, cross-over study

The tolerability and pharmacokinetics of a new controlled-release (CR) formulation of carbamazepine (CBZ), were assessed in a multicentre, double-blind, cross-over trial, carried out in 48 epileptic patients (21 men, 27 women; mean age 34.2 years) on conventional CBZ monotherapy, but without complete seizure control (n = 22) or with intermittent side effects (n = 4), or with both (n = 22). Eligible patients were randomized to conventional CBZ or CR CBZ, each given in sequence at individualized daily doses, subdivided into the lowest number of administrations. Each period of the cross-over consisted of a first phase of optimal dose finding (lasting up to two months) and a second one of maintenance (lasting one month) used for evaluation. At the end of each period, a 10-h plasma CBZ and CBZ-epoxide concentration profile, as well as the tolerability and the efficacy of the drugs, were evaluated. The mean CBZ daily dose increased by 16% during the administration of the CR formulation. Fluctuations of total CBZ and 10, 11-epoxide plasma level daily profiles at steady-state were significantly (p less than 0.001) lower during CR CBZ treatment, leading to a significant (p less than 0.001) decrease in intermittent side effects (6 patients on CR CBZ vs 26 on conventional CBZ). Finally, 38 patients on CR CBZ (vs 15 patients on conventional CBZ) were treated with a b.i.d. regimen.     

Effect of associated antiepileptic treatment on valproate-induced hyperammonemia

It has recently been shown that acute changes of venous blood ammonia (NH3) may predict short-term adverse effects of valproic acid (VPA). In the present study, the time course of NH3 concentration after a single oral dose of VPA (800 mg) was monitored in 68 epileptic patients. Patients were classified into four groups: previously untreated patients (group A, n = 21), patients under treatment with either phenobarbital (group B, n = 14) or phenytoin (group C, n = 13) or both (group D, n = 20). In each patient, venous blood for the NH3 assay was taken before the VPA dose (predose level) and at 1, 2, 3, and 4 h after the dose (postdose levels). While in patients receiving only VPA the postdose NH3 concentrations did not differ from the predose level, in each of groups B, C, and D the postdose concentrations appeared to be significantly higher than the predose concentration. The greatest increase was observed in group D. In the light of the data reported in the literature, those patients whose NH3 concentration after the VPA dose exceeds 100 micrograms/dl should be considered at higher risk for short-term, VPA-induced adverse effects during long-term therapy. Thus, our data suggest that caution should be exercised in adding VPA to anticonvulsant treatments including phenobarbital or phenytoin or both.     

Colonoscopic control of uretero-enteric anastomoses in internal urinary diversion

Twenty-four patients with internal urinary diversion following total bladder ablation underwent colonoscopic control of the uretero-enteric anastomoses. The techniques performed were: rectal bladder with colostomy according to Mauclaire (11 patients); rectal bladder with abdomino-perineal pull-through according to Heitz-Boyer/Hovelacque (6); ureterosigmoidostomy (7). The uretero-enteric anastomoses were divided into 3 categories according to the colonoscopic appearance: "nipple-like", nearly flat and flat anastomosis. Urographic examinations were carried out in all patients and the results demonstrated that the "nipple-like" anastomosis was the most successful for the preservation of upper urinary tract integrity.     

Neurological adverse events of new generation sodium blocker antiepileptic drugs. Meta-analysis of randomized,double-blinded studies with eslicarbazepine acetate,lacosamide and oxcarbazepine

PurposeAnalysis of overall tolerability and neurological adverse effects (AEs) of eslicarbazepine acetate (ESL), lacosamide (LCM) and oxcarbazepine (OXC) from double-blind, placebo-controlled trials. Indirect comparisons of patients withdrawing because of AEs, and the incidence of some vestibulocerebellar AEs between these three antiepileptic dugs (AEDs).MethodsWe searched MEDLINE for all randomized, double-blind, placebo-controlled trials investigating therapeutic effects of fixed oral doses of ESL, LCM and OXC in patients with drug resistant epilepsy.Withdrawal rate due to AEs, percentages of patients with serious AEs, and the proportion of patients experiencing any neurological AE, nausea and vomiting were assessed for their association with the experimental drug.Analyses were performed between recommended daily doses of each AED according to the approved summary of product characteristics (SPC). Risk differences were used to evaluate the association of any AE [99% confidence intervals (CIs)] or study withdrawals because of AEs (95% CIs) with the experimental drug. Indirect comparisons between withdrawal rate and AEs dizziness, coordination abnormal/ataxia and diplopia were estimated according to network meta-analysis (Net-MA).ResultsEight randomized, placebo-controlled, double-blind trials (4 with ESL, 3 with LCM, and 1 with OXC) were included in our analysis.At high doses (OXC 1200 mg, ESL 1200 mg and LCM 400 mg) there was an increased risk of AE-related study withdrawals compared to placebo for all drugs. Several AEs were associated with the experimental drug. Both number and frequency of AEs were dose-related.At high recommended doses, patients treated with OXC withdrew from the experimental treatment significantly more frequently than patients treated with ESL and LCM. Furthermore, the AEs coordination abnormal/ataxia and diplopia were significantly more frequently observed in patients treated with OXC compared to patients treated with LCM and ESL.ConclusionsThe overall tolerability of AEDs and the incidence of several neurological AEs were clearly dose-dependent. Indirect comparisons between these AEDs, taking into account dose-effect, showed that OXC may be associated with more frequent neurological AEs than LCM and ESL.     

Involvement of the human dorsal premotor cortex in unimanual motor control: an interference approach using transcranial magnetic stimulation

Unilateral movements are enabled through a distributed network of motor cortical areas but the relative contribution from the parts of this network is largely unknown. Failure of this network potentially results in mirror activation of the primary motor cortex (M1) ipsilateral to the intended movement. Here we tested the role of the right dorsal premotor cortex (dPMC) in 11 healthy subjects by disrupting its activity with 20 Hz repetitive transcranial magnetic stimulation (rTMS) whilst the subjects exerted a unilateral contraction of the left first dorsal interosseous (FDI). We found that disruption of right dPMC enhanced mirror activation of the ipsilateral left M1, as probed by motor evoked potential (MEP) amplitude to the right FDI. This was not the case with sham rTMS, when rTMS was directed to the right M1, or with rTMS of the right dPMC but without contraction of the left FDI. Findings suggest that activity in the dPMC contributes to the suppression of mirror movements during intended unilateral movements.     

Vigabatrin-induced decrease in serum phenytoin concentration does not involve a change in phenytoin bioavailability

The possibility that vigabatrin (VGB) decreases serum phenytoin (PHT) concentration by lowering the oral bioavailability of PHT was investigated in 21 patients with epilepsy. Each patient was switched from oral to intravenous PHT for 5 days before and after combined treatment with VGB. After VGB (2-3.5 g day(-1) for at least 5 weeks), serum PHT concentrations decreased slightly from 87 +/- 25 to 76 +/- 31 micromol l(-1) (means +/- s.d., P < 0.05), but in a subgroup of seven patients the decrease was more prominent (from 72 +/- 22 to 49 +/- 17 micromol l(-1), P < 0.005). At baseline (before VGB), serum PHT remained unaffected (85 +/- 30 micromol l(-1)) after switching PHT dosage to the intravenous route, indicating that the oral availability of the drug was virtually complete. During VGB treatment, serum PHT was also unchanged (74 +/- 34 micromol l(-1)) after switching from oral to intravenous therapy, and this was also true for the subgroup of patients showing a prominent interaction (48 +/- 18 micromol l(-1)). The urinary recoveries of PHT and its metabolites pHPPH and mHPPH remained constant throughout the study. It is concluded that the oral availability of PHT is unaffected by VGB and that the VBG-induced decrease in serum PHT is mediated by alternative mechanisms.     

Lacosamide in patients with pharmacoresistant epilepsy

Introduction: Lacosamide is a novel antiepileptic drug licensed in the US and Europe as adjunctive therapy for partial-onset seizures in adults. The efficacy, safety, tolerability and favorable pharmacokinetic profile in the adult population suggest that lacosamide could be of benefit for patients with partial-onset seizures. Areas covered: This paper reviews the available evidence and most recent data concerning the efficacy, safety, tolerability and pharmacokinetics of lacosamide in adults, as well as in the pediatric population. Expert opinion: Lacosamide is one of the newest drugs of the antiepileptic armamentarium, and it is expected to compete directly with compounds that are currently used for adjunctive therapy in adults with refractory partial epilepsy. The intravenous formulation may be used for replacement therapy in patients temporarily unable to take oral medication. An apparent lack of sedative or cognitive effects might render this drug preferable in patients with mental insufficiency and/or epileptic encephalopathy.     

Circulating cell-free DNA in plasma of melanoma patients: qualitative and quantitative considerations

DNA integrity in blood is an emerging biomarker in cancer. Here we report a real time PCR approach for the absolute quantification of four amplicons of 67, 180, 306 and 476 bp in cutaneous melanoma. Three different integrity indexes (180/67, 306/67 and 476/67 ratios) were tested for their ability to reflect differences in plasma cell-free DNA (cfDNA) fragmentation in 79 patients affected by cutaneous melanoma and 34 healthy subjects. All the three integrity indexes showed higher values in melanoma patients in comparison with healthy subjects. According to ROC curve analysis, the ratio 180/67 is the most suitable index to be used in cancer patient selection, even if the combination of the 3 indexes gives the best performance in terms of clinical sensitivity. The most represented fragments in plasma of melanoma patients are those comprised between 181 and 307 bp, while in healthy subjects there is a prevalence of shorter fragments (67-180 bp). In conclusion, DNA integrity indexes can be considered suitable parameters for monitoring cfDNA fragmentation in melanoma patients.     

The adverse event profile of pregabalin across different disorders: a meta-analysis

Purpose

In a recent meta-analysis of 38 double-blind randomized controlled trials (RCTs) comparing pregabalin (PGB) to placebo, we found 20 adverse events (AEs) to be significantly associated with PGB treatment. In the present study, we evaluated whether the incidence of these 20 AEs differs across distinct disorders in which PGB was investigated.

Methods

Among the 38 previously identified RCTs of PGB, we selected only those including a PGB 600?mg/day arm and subsequently classified them into four distinct groups according to the disorder in which PGB was investigated: (1) drug-resistant partial epilepsy, (2) psychiatric disorders, (3) fibromyalgia, and (4) neuropathic pain. We used risk differences (RDs) to quantify the placebo-corrected proportion of subjects discontinuing PGB due to intolerable AEs and to determine the placebo-corrected incidence of each of the 20 PGB AEs across the four disorders.

Results

Twenty-two RCTs were included in this study. Neither the proportion of subjects discontinuing PGB due to intolerable AEs nor the incidence of PGB AEs (with the exception of ataxia) differed significantly across the four disorders. Ataxia was more common in drug-resistant partial epilepsy compared to fibromyalgia. When limiting analyses to subjects on placebo, most vestibulo-cerebellar AEs (ataxia, diplopia, and blurred vision) were found to be more common in drug-resistant partial epilepsy compared to all other disorders. Diplopia and blurred vision were more common in epilepsy than in neuropathic pain; and ataxia had a higher incidence in epilepsy than in anxiety disorder and fibromyalgia. Among other CNS AEs, somnolence was more common in epilepsy compared to neuropathic pain and in anxiety disorders alone compared to neuropathic pain and fibromyalgia. Asthenia was also more common in epilepsy than in neuropathic pain and fibromyalgia.

Conclusions

Although drug-resistant partial epilepsy is associated with a higher probability of developing vestibulo-cerebellar AEs, the risk for PGB toxicity does not differ across distinct disorders.