Clinical manifestations of Pacak‐Zhuang syndrome in a male pediatric patient

We report an index case of a male patient who presented with all clinical manifestations of Pacak‐Zhuang syndrome, including early‐age polycythemia, multiple pheochromocytomas/paragangliomas, duodenal somatostatinoma, and ocular findings. Sequencing analysis detected an EPAS1 mutation in all tumors tested, but not in the germline.     

Research on medication use in the neonatal intensive care unit

Introduction: Research on medication use aims at assessing how much of current pharmacotherapy is rational. In neonates, this is hampered by extensive off-label drug use and limited knowledge.

Areas covered: We report on medication use research and have conducted a systematic review of observational studies on medication use to provide an updated overview on characteristics, objectives, methods, and patterns in hospitalized neonates. Moreover, a review on aspects of medication use for opioids, anti-epileptics, gastric acid-related disorders and respiratory stimulants with emphasis on trends and impact of interventions is presented, illustrating how research on medication use can contribute to improved neonatal pharmacotherapy and more focused research. Medication use reports describe patterns and provide signals on irrational use, benchmarking, or can guide research priorities. Moreover, this may generate information on how neonatal health topics and their pharmacotherapy are handled over time or across regions.

Expert opinion: Research on medicine utilization is relevant, since it will inform us on aspects like trends, variability, or about the impact and pattern of implementation of guidelines in neonates. Further progress necessitates to merge datasets on medication use with clinical characteristics, and perinatal drug use remains an area in need of additional research.     

Emergencies caused by pheochromocytoma, neuroblastoma, or ganglioneuroma.

Pheochromocytoma may lead to important emergency situations, ranging from cardiovascular emergencies to acute abdomen and multiorgan failure. It is vital to think about this disease in any emergency situation when conventional therapy fails to achieve control or symptoms occur that do not fit the initial diagnosis. The importance of keeping this diagnosis in minds is underscored by the fact that, in 50% of pheochromocytoma patients, the diagnosis is initially overlooked. Two other tumors of the sympathetic nervous system, neuroblastoma and ganglioneuroma, are less commonly associated with emergency conditions. If they occur, they are often linked to catecholamine excess, paraneoplastic phenomena, or local tumor mass effect.     

Cytochrome P450 3A4 and P-glycoprotein Activity and Assimilation of Tacrolimus in Transplant Patients with Persistent Diarrhea

Renal transplant recipients suffering from persistent diarrhea have been repeatedly reported to have increased tacrolimus (Tac) trough levels. This study aimed to explore this phenomenon in detail in 15 renal transplant recipients with diarrhea, whose immunosuppression consisted of corticosteroids, mofetil mycophenolate and Tac. Both hepatic and intestinal CYP3A4 and PGP activity, important determinants of Tac bioavailability, were assessed, together with global CYP activity and investigations for gastrointestinal infection, function and morphology. Global CYP, CYP3A4, PGP and trough/dose levels of Tac were compared with diarrhea-free controls. In addition, a pharmacokinetic study of Tac was performed in 11 patients affected by diarrhea versus 9 controls. As expected, diarrhea was associated with increased Tac trough levels. An even stronger, significant increase of dose-normalized Tac levels was observed between 90 and 360 min after Tac intake. Time to peak concentration and drug half-life, however, were not altered. In addition, a concomitant decrease (+/-50%) of intestinal PGP activity was noticed in patients with diarrhea. For global CYP, CYP3A4 and hepatic PGP activity no such differences were noted. This pattern was not influenced by the specific cause of diarrhea. These data strongly suggest that persistent diarrhea is associated with an increased oral bioavailability of Tac.     

The effect of liquid silicone on the corneal endothelium in rabbits

Specular microscopic and histopathologic findings in the corneal endothelium were compared after the injection of liquid silicone into the anterior chamber of both eyes in 15 rabbits. The findings demonstrated serious damage to the endothelium in the area of contact of liquid silicone with the posterior surface of the cornea and disclosed some problems in the interpretation of specular microscopic findings. An abnormal endothelial mosaic can be probably found even in a zone of preserved intercellular borders or in a zone with a relief of the bases of extinct endothelial cells.     

Polymerizable amphiphiles, 2. Micellization of 1-O-3-(4-vinylphenyl)propyl-β-D-glucopyranose

1-O-3-(4-Vinylphenyl)propyl-β-D -glucopyranose ( 1 ) undergoes in water a closed association under formation of N-mers. The unimer/N-mer association is directly visible in the Schlieren pattern of ultracentrifugal synthetic boundary experiments. Association numbers and mass-concentration-based equilibrium constants of association were calculated from the variation of N-mer concentrations with unimer concentrations and from the concentration dependence of inverse apparent average molar masses as measured by both vapor phase osmometry and sedimentation equilibrium. Association numbers were also calculated from the combination of sedimentation coefficients with diffusion coefficients, sedimentation coefficients with intrinsic viscosities, and diffusion coefficients with interinsic viscosities as well as from the dependence of apparent mass-average molar masses on inverse apparent number-average molar masses. All methods gave in general different association numbers and equilibrium constants. The effect, which was not found for other non-ionic amphiphiles, is probably due to the existence of consecutive equilibria between the unimer and a low molar mass P-mer which associates to a higher molar mass R-mer. Viscosity data are in agreement with the picture of a spherical micelle for the dominant P-mers with about 10 water molecules per glucose residue. The micellization of 1 is both enthalpy- and entropy-driven, in contrast to the micellization of 1-O-octyl-β-D -glucopyranose which is a strictly entropy-driven process.     

Influence of a serotonin- and dopamine-rich diet on platelet serotonin content and urinary excretion of biogenic amines and their metabolites.

Using high-performance liquid chromatography and gas chromatography, we reevaluated the 24-h influence of a serotonin- and dopamine-rich diet on platelet serotonin and serotonin, 5-hydroxyindoleacetic acid (5-HIAA), and major catecholamine metabolites in the urine of 15 healthy adults. Although there were significant responses in urinary free serotonin and catecholamine metabolites, their concentrations did not exceed the upper limits of the reference ranges for any of the participants. For urinary 5-HIAA, pronounced effects were observed within 2-4 h. After 6-8 h, results for 11 participants exceeded the upper limit of the reference range. The median recovery of dietary serotonin as urinary 5-HIAA was 20% and subject to a large range (1-50%). There was no significant change in platelet serotonin. We conclude that, using specific analytical methods, no dietary restrictions need be imposed to diagnose catecholamine (metabolite)-producing tumors. For diagnosis of carcinoids on the basis of urinary 5-HIAA it is appropriate to completely abstain from serotonin-containing foods for greater than or equal to 12 h before testing. Platelet serotonin is a more sensitive marker for carcinoids that produce only small amounts of serotonin, and is unaffected by dietary serotonin.     

Treatment of diabetic polyneuropathy with the neurotrophic peptide ORG 2766

The efficacy of the neurotrophic peptide ORG 2766 in diabetic patients with polyneuropathy was evaluated in a double-blind, placebo-controlled, multicentre trial. One hundred and twenty four patients were randomised in five groups to receive 0.1, 0.4, 2 or 5 mg ORG 2766 or placebo, once daily, administered subcutaneously 52 weeks. Thermal discrimination thresholds (TDT) and vibration perception thresholds (VPT), motor and sensory nerve conduction velocity, Hoffmann reflex, heart rate variation during deep breathing and heart rate response after standing up, neurological examination score and neuropathic symptom score were determined at baseline and after 17, 34 and 52 weeks of treatment. Of the nerve function indices studied, at week 52 the TDT_warmth of the hand in the ORG 2766 0.1, 0.4 and 5 mg groups and the TDT_cold of the foot in the ORG 2766 0.1 and 0.4 mg groups significantly improved compared with placebo. Further significant improvement as compared with placebo was observed in the paraesthesia score at week 34 and week 52 in the ORG 2766 2 mg group. Only at week 34 had both the heartbeat variation during deep breathing and the VPT of the foot in the ORG 2766 0.1 mg group improved significantly, compared with placebo. No further statistically significant differences were observed at time for the other measures. No adverse reactions were observed. The only recorded drug-induced side effect was pain at the injection site. Taking all measures of efficacy into account, the statistically significant results observed did not show consistency within each measure. Therefore, it is concluded that ORG 2766, in contrast to earlier reports, is not effective in treating diabetic polyneuropathy.