Approach to seizures in the neonatal period: a European perspective

In the neonatal period, seizures rank among the most common neurological symptoms, often indicating an underlying serious neurological condition. It is remarkable that although new tools have been incorporated into the diagnosis of neonatal seizures, there is no consensus about the therapeutic approach among different doctors and institutions. Hence, although phenobarbital is still considered the initial drug of choice, the protocols reported in the literature show a great variability in the approach to treatment of refractory seizures. We used a questionnaire to gain information regarding the treatment of seizures in the neonatal period in different European institutions. Conclusion: We conclude that phenobarbital is still the initial drug of choice followed by benzodiazepines, except in preterm infants with a birth weight below 1800 g. In refractory seizures, the use of continuous lidocaine infusion is most common. Of note, clinical studies with newer drugs have been mostly performed in the United States but not in Europe.     

Induction of apoptosis by arachidonic acid in human retinoblastoma Y79 cells: involvement of oxidative stress

Arachidonic acid administration caused apoptosis in Y79 cells, as shown by typical morphological changes, phosphatidylserine externalization, chromatin condensation, processing and activation of caspase-3 and cleavage of the endogenous caspase substrate poly-(ADP-ribose)-polymerase. Arachidonic acid also caused lamin B cleavage, suggesting caspase-6 activation. Arachidonic acid treatment was accompanied by increased formation of the lipid peroxidation end products malondialdehyde and 4-hydroxy-2-nonenal, lowering in reduced glutathione content and in mitochondrial membrane potential. Inhibiting glutathione synthesis sensitized Y79 cells to apoptosis-inducing stimuli, whilst replenishing reduced glutathione attenuated arachidonic acid toxicity. Similar findings were obtained using hydroperoxyeicosatetranoic acids (oxygenated metabolites of arachidonic acid which deplete the reduced glutathione pool) and nordihydroguaretic acid, a general inhibitor of lipooxygenase pathway. which may also trigger rapid depletion of reduced glutathione. Melittin, which is known to activate phospholipase A2, also potently induced apoptosis. Arachidonic acid toxicity was inversely related to cell density. This could depend on an increased production of molecules with antiapoptotic effect; insulin-like growth factors could most likely be one of these molecules. These results propose a role for oxidative stress in the cytotoxicity induced by arachidonic acid in Y79 cells and suggest that these cells could be protected from such toxicity as long as sufficient levels of reduced glutathione and survival factors are present.     

Modified technique for safer indocyanine-green-assisted peeling of the internal limiting membrane during vitrectomy for macular hole repair

Background During macular hole surgery, indocyanine green (ICG) has access to the subretinal space and can lead to toxic and phototoxic damage of the retinal pigment epithelium (RPE). To reduce its toxicity and to avoid contact between ICG and the RPE, we have developed a modified technique by using autologous whole blood.Methods Thirty-one eyes underwent vitrectomy for idiopathic macular hole repair. Autologous whole blood (0.1 ml) was injected into the buffered saline solution (BSS)-filled vitreous cavity over the posterior pole and aspirated with a flute cannula. A small clot remained covering the macular hole. The internal limiting membrane (ILM) was stained by using 0.05% ICG solution. The ICG was dissolved in 5% glucose to obtain an iso-osmotic solution. This ICG was injected into the BSS-filled vitreous cavity over the posterior pole and removed after 10 s. The ILM was peeled and a long-acting gas tamponade applied. Pre- and postoperative best-corrected visual acuity and optical coherence tomography (OCT) findings are reported.Results Macular hole closure was achieved in 30 of 31 eyes (97%). The mean preoperative logMAR acuity was 0.99 (range: 0.4 to 2.0). Mean postoperative logMAR acuity was 0.496 (range: 0.0 to 1.0). The average improvement in vision was 0.66 logMAR units (range: 1.5 to 0.0). No postoperative RPE alterations were observed biomicroscopically or on OCT.Conclusion This surgical technique leads to favorable anatomic and functional results. ICG toxicity is reduced by modifying osmolarity, concentration and contact time and by injecting ICG under BSS. Autologous whole blood acts as a mechanical barrier and prevents ICG from entering in the subretinal space.This article is original and has not been published previously.The authors have no financial interest related to this publication and transfer all copyright to the publisher upon acceptance.     

25-gauge, sutureless vitrectomy and standard 20-gauge pars plana vitrectomy in idiopathic epiretinal membrane surgery: a comparative pilot study

Background The aim of the study was to evaluate the safety and functional outcome of a small incision, sutureless vitrectomy in the treatment of idiopathic epiretinal membranes (ERM) compared with a standard 20-gauge vitrectomy system.Methods Forty-six consecutive patients with idiopathic ERM were recruited for this study and prospectively evaluated. In group 1 (n=26) we used a transconjunctival sutureless 25-gauge vitrectomy system (TSV), patients in group 2 (n=20) were operated on using a standard 20-gauge vitrectomy system. The ERM was removed and the internal limiting membrane (ILM) was peeled in all eyes. Surgery-related complications, operating time, intraoperative balanced salt solution (BSS) consumption, postoperative discomfort, postoperative intraocular inflammation, lens opacification, and long-term visual outcome are reported and compared.Results No surgery-related complications were observed in either group. Operating time was shorter in group 1 compared with group 2 (mean 15.6 and 29.6 min respectively). Intraoperative amount of BSS consumption was less in group 1 (mean 28 ml in group 1 and 42 ml in group 2). Postoperative discomfort and intraocular inflammation were significantly reduced in the 25-gauge group. In the 20-gauge group cataract formation requiring surgery was observed in two eyes. Visual acuity improved significantly in both groups. The 25-gauge group improved on average by more lines of vision and the improvement in vision was more rapid.Conclusion The TSV system is a safe and efficient surgical technique for ERM surgery. Operating time is significantly reduced, minimizing surgery-induced trauma, and reducing postoperative intraocular inflammation and the patients’ discomfort. The incidence of cataract formation may be less using TSV. Postoperative recovery is accelerated.The authors have no financial interests related to this publication.     

Benzo[a]pyrene at an environmentally relevant dose is slowly absorbed by, and extensively metabolized in, tracheal epithelium

While tobacco smoke has been conclusively identified as a lung carcinogen, there is much debate over which smoke constituent(s) are primarily responsible for its carcinogenicity. Previous studies in our laboratory suggested that highly lipophilic carcinogens are slowly absorbed in the thicker epithelium of the conducting airways, potentially allowing for substantial local metabolism. The bioactivation of polycyclic aromatic hydrocarbons in airway epithelium may, hence, be important in tobacco smoke-induced carcinogenesis. In the present study, the hypothesis of slow absorption and substantial local metabolic activation of highly lipophilic carcinogen in airway epithelium was tested in dogs. A single dose of tritiated benzo[a]pyrene (BaP) dissolved in a saline/phospholipid suspension was instilled in the trachea, just anterior to the carina. At intervals of a few minutes up to 30 min over a 3-h period, blood samples were drawn from the azygous vein, which drains the area around the point of instillation, and from the systemic circulation. Tissue samples were taken at the end of the experiment. The concentration of BaP with depth into the tracheal mucosa was determined with autoradiography. BaP was slowly absorbed into the trachea with a half-time of approximately 73 min, which is consistent with diffusion-limited passage through the epithelium and lead to local doses in the tracheal epithelium that were more than a 1000-fold those of other tissues. The long retention of BaP in the epithelium provided the local metabolizing enzymes with high substrate levels over a long period, resulting in extensive metabolism. At 3 h after the exposure, 23% of the BaP-equivalent activity remained in the tracheal mucosa. Of this fraction, 13% was parent compound, 28% was organic extractable, 31% was water-soluble, and 28-7% of the instilled dose was bound to tracheal tissues. These results explain the tendency of highly lipophilic carcinogens, such as BaP, to induce tumors at the site of entry and, furthermore, indicate that the highly lipophilic components of tobacco smoke and polluted air may be the most important contributors to lung tumors of the conducting airways.      

Need for follow up in coeliac disease

The use of follow up studies was evaluated in 128 patients with coeliac disease during their first visit to a department for adults. The original diagnosis had been made in childhood in all patients. Fifty eight (45%) of the subjects were following a gluten free diet, 23 (18%) were following a gluten free diet but with occasional gluten consumption, and 47 (37%) had adopted an unrestricted, gluten containing diet for a mean of 11.2 years. There was no correlation in individual subjects between the presence of symptoms, biochemical and immunological abnormalities, severity of histological findings, and the amount of dietary gluten, despite the greater frequency of symptoms in the group following an unrestricted diet than in the other two groups. Short stature and epilepsy with cerebral calcifications only occurred in patients following an unrestricted diet. As only diagnosis based on two or three biopsy samples and regular follow up correlated positively with dietary compliance, it is suggested that a histologically confirmed diagnosis of coeliac disease and regular lifelong follow up are essential in the management of these patients.     

Elderly Patients with Suppressed Serum TSH but Normal Free Thyroid Hormone Levels Usually Have Mild Thyroid Overactivity and are at Increased Risk of Developing Overt Hyperthyroidism

The clinical and biochemical characteristics of 15 elderly patientswith low levels of thyrotrophin (TSH) (<0.1 mU/L) but normalfree tri-iodothyronine, (T3) and free thyroxine (T4) (groupS) were compared with 10 euthyroid subjects (group E) and 10hyperthyroid patients (group T). Free T3 and free T4 were significantlyhigher (p<0.05) in group S(6.3±0.5 and 18.6±1.0pmol/l, respectively) than in group E(4.6±0.3, 12.6+0.6).In common with elderly hyperthyroid patients (group T)patientsin group S had few signs or symptoms of thyrotoxocosis, butthe Wayne score (clinical index of hyperthyroidism) was higherin group S than in euthyroid subjects (p<0.05). Thyroid microsomal,thyrogolobulin or thyrotrophin receptor antibodies were commonin group T (n=9)but not in groups S(n=2) or E(n=1). This suggestsa low prevalence of Graves' disease in group S compared to groupT. Combined thyrotrophin releasing hormone (TRH; 200 µgi.v.) and gonadotrophin releasing hormone GnRH; 100 µgi.v.) tests were performed; no cases of low TSH due to hypopituitarismwere identified in group S. During a mean of 7.9 (4–12)months of observation TSH reverted to the normal range (>0.2mU/L)in 7 of 15 patients in group S; thyroid hormone concentrationsrose above the normal range in four, however, only two patientsrequired treatment for hyperthyroidism. It is unlikely thatthe suppressed TSH of patients in group S was due to mild thyroidhormone excess; although this is often a transitory phenomenon,these patients are at increased risk of developing overt hyperthyroidism.