Early indicators of chronic lung disease in preterm infants with respiratory distress syndrome and their inhibition by melatonin

Improved survival from advances in neonatal care has resulted in an increased number of infants at risk for chronic lung disease (CLD). Recently, it was reported that inflammatory mediators such as interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha and IL-8 are present in higher concentrations in lung lavage from babies who develop CLD. Previously, we found that melatonin reduced the rises in proinflammatory cytokines (IL-6, IL-8 and TNF-alpha) and nitrite/nitrate levels in the serum of preterm newborns with respiratory distress syndrome (RDS). The values correlated with gestational age and iatrogenic trauma in the form of oxygen exposure and mechanical ventilation. Increased concentrations of proinflammatory cytokines may, therefore, be the most valuable early indicator of developing CLD and these measurements may assist in selecting infants for interventions such as melatonin treatment or more selective blockage of components of inflammation. In the current study, we extend the original observations and report results in which 120 newborns diagnosed with RDS were either treated with melatonin (60 children) or given placebo (60 children). The cytokine measures were consistent with the previously reported findings and showed that melatonin reduced these values and also lowered nitrite/nitrate levels in serum of newborns with respiratory distress. Furthermore, when nonmelatonin-treated newborns who developed CLD (eight infants) were examined separately, they had levels of IL-6, IL-8, TNF-alpha and nitrite/nitrate values much higher than those in children who did not develop CLD. Two of the nonmelatonin-treated newborns died while no children who received melatonin died. Melatonin was well tolerated by the newborns.     

IL-6 Receptor Blockade by Tocilizumab Has Anti-absence and Anti-epileptogenic Effects in the WAG/Rij Rat Model of Absence Epilepsy

Increased expression of interleukin-6 (IL-6) both in cerebrospinal fluid (CSF) and plasma is closely associated with convulsive epilepsy and symptom severity of depression. By comparison, at present, little is known about the role of this cytokine in childhood (non-convulsive) absence epilepsy. The aim of this work was to investigate the potential effects of acute and chronic treatment with tocilizumab (TCZ, 10 and 30 mg/kg/day), on absence seizures, their development, and related psychiatric comorbidity in WAG/Rij rats. It is known that lipopolysaccharide (LPS)-induced changes in inflammatory processes increase absence epileptic activity. In order to study the central effects of TCZ, we investigated whether administration of this anti-IL-6R antibody could modulate the lipopolysaccharide (LPS) or IL-6-evoked changes in absence epileptic activity in WAG/Rij rats. Our results demonstrate that TCZ, at both doses, significantly reduced the development of absence seizures in adult WAG/Rij rats at 6 months of age (1 month after treatment suspension) compared with untreated controls, thus showing disease-modifying effects. Decreased absence seizure development at 6 months of age was also accompanied by reduced comorbid depressive-like behavior, whereas no effects were observed on anxiety-related behavior. Acute treatment with TCZ, at 30 mg/kg, had anti-absence properties lasting ~25 h. The co-administration TCZ with i.c.v. LPS or IL-6 showed that TCZ inhibited the worsening of absence seizures induced by both proinflammatory agents in the WAG/Rij rats, supporting a central anti-inflammatory-like protective action. These results suggest the possible role of IL-6 and consequent neuroinflammation in the epileptogenic process underlying the development and maintenance of absence seizures in WAG/Rij rats. Accordingly, IL-6 signaling could be a promising pharmacological target in absence epilepsy and depressive-like comorbidity.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00893-8) contains supplementary material, which is available to authorized users.Key Words: Absence epilepsy, epileptogenesis, neuroinflammation, tocilizumab, depressive-like behavior, anxiety.     

Electrophysiologic evaluation of intravenous nicardipine in man

The acute electrophysiological effects of intravenous nicardipine (0.014 mg/kg per min for 5 minutes) were studied in 12 subjects with estimated normal sinus node functions and atrioventricular conduction parameters. The most important effects were sinus cycle length shortening, increase of corrected sinus node recovery time and reduction of effective and functional refractory period of the atrioventricular node. Sinuatrial conduction time, atrial refractory periods, intranodal conduction, bundle branch refractoriness and ventricular refractoriness were unchanged. Systolic and diastolic blood pressure was reduced. The clinical implications of these properties of the drug are discussed and compared with those of verapamil, diltiazem and nifedipine.     

Pediatric Burkitt lymphoma presenting as acute pancreatitis: MRI characteristics

Acute pancreatitis is a rare initial presentation of non-Hodgkin lymphoma with few reported cases described in older adults and even fewer in children. MRI features of Burkitt lymphoma of the pancreas are sparse in the radiologic literature. We present a 6-year-old boy who presented with pancreatitis and obstructive jaundice, which was the result of Burkitt lymphoma of the pancreas. The imaging findings of pancreatic involvement of Burkitt lymphoma on MRI are discussed and the contributory role of the radiologist in guiding the appropriate clinical work-up of this disease is highlighted.     

Defecography and treatment of essential anal pain

INTRODUCTION: Proctalgia is a chronic anal pain in the absence of any organic conditions of the anorectum and excluding such morphofunctional disorders as rectal prolapse, intussusception and solitary rectal ulcer, which are easily shown with defecography but not with other imaging techniques. Proctalgia patients undergo a long workup and many instrumental and radiologic examinations and are finally referred to the proctologist with a condition which is difficult to diagnose and treat. We investigated the defecographic findings and anorectal abnormalities of essential proctalgia, as well as the correlation between radiologic findings, clinical symptoms and efficacy of biofeedback treatment. MATERIALS AND METHODS: We retrospectively examined 31 patients (21 women and 10 men; age range: 25-67 years, mean: 46) with defecography, clinico-proctologic investigations integrated with anoscopy and sigmoidoscopy, anorectal manometry and psychological tests. The women were submitted to gynecologic examination: 8 patients had a history of anorectal and pelvic surgery. We did not perform anal electromyography because it may cause painful sphincterial spasms. All patients underwent 30-minute weekly sessions of biofeedback till regression of symptoms. RESULTS: Anal pain was described as anorectal in 18 cases, anoperineal in 7, anosphincterial in 5 and rectovaginal in 1 case. It radiated to the sacrum in 42% of cases, thighs in 23%, gluteus muscles in 19%, and was related to evacuation in 39% of cases. Pain lasted some hours (58%) to a few minutes (42%). Manometric data showed sphincterial hypertonia in 14 patients. Eleven patients suffered from anxiety and were on drug treatment. Defecography demonstrated rectocele in 15 cases, puborectalis muscle syndrome in 14, external sphincter spasm in 12, perineal descent in 8, rectal muscosal prolapse in 4, intussusception in 3 and fecal incontinence in 2 cases. After 10 weeks of biofeedback training, all patients reported improvement of symptoms, which was confirmed at manometry as reduced sphincterial pressure. CONCLUSIONS: The etiology of essential proctalgia is unknown, but functional disorders of the pelvic floor and sphincterial muscles, as well as altered perineal stasis and pudendal conditions, all play an important role. These data are confirmed in our study where puborectalis syndrome, external sphincterial spasm and perineal descent are involved in over 70% of cases. Defecography is a useful tool because it permits to diagnose abnormal anorectal morphology and to diagnose sphincterial and puborectalis muscle dysfunctions which are missed with other instrumental and imaging techniques.     

An analysis of “long-term” follow-up results in patients with cervical intraepithelial neoplasia treated by cryotherapy

Two thousand eight hundred thirty-nine patients who had been treated by cryotherapy for cervical intraepithelial neoplasia (CIN) in nine different institutions were followed longitudinally after three negative Papanicolaou smears to ascertain the risk of recurrence. The cumulative risk of developing CIN after successful cryotherapeutic management of CIN was 0.41% at year 10, and 0.44% at year 14. There was no significant difference in risk between patients originally treated for CIN 1, CIN 2, or CIN 3.