Binge eating in Parkinson's disease: prevalence, correlates and the contribution of deep brain stimulation

Of 96 Parkinson's disease patients surveyed at the University of Florida Movement Disorders Center, one (1%) met diagnostic criteria for binge-eating disorder. Eight (8.3%) exhibited subthreshold binge eating. Psychometric criteria classified problem gambling in 17.8%, hoarding in 8.3%, compulsive buying in 11.5%, hypersexuality in 1.0%, and mania in 1.0% of patients. More overeaters met psychometric criteria for at least one additional impulse-control disorder (67% versus 29%). No more overeaters than non-overeaters were taking a dopamine agonist (44% versus 41%). More overeaters had a history of subthalamic deep brain stimulation (DBS; 44% versus 14%). History of DBS was the only independent predictor of overeating.     

Substance P and vasoactive intestinal peptide are reduced in right transverse colon in pediatric slow‐transit constipation

Background Slow‐transit constipation (STC) is recognized in children but the etiology is unknown. Abnormalities in substance P (SP), vasoactive intestinal peptide (VIP) and nitric oxide (NO) have been implicated. The density of nerve fibers in circular muscle containing these transmitters was examined in colon from children with STC and compared to other pediatric and adult samples. Methods Fluorescence immunohistochemistry using antibodies to NO synthase (NOS), VIP and SP was performed on colonic biopsies (transverse and sigmoid colon) from 33 adults with colorectal cancer, 11 children with normal colonic transit and anorectal retention (NAR) and 51 with chronic constipation and slow motility in the proximal colon (STC). The percentage area of nerve fibers in circular muscle containing each transmitter was quantified in confocal images. Key Results In colon circular muscle, the percentage area of nerve fibers containing NOS > VIP > SP (6 : 2 : 1). Pediatric groups had a higher density of nerve fibers than adults. In pediatric samples, there were no regional differences in NOS and VIP, while SP nerve fiber density was higher in sigmoid than proximal colon. STC children had lower SP and VIP nerve fiber density in the proximal colon than NAR children. Twenty‐three percent of STC children had low SP nerve fiber density. Conclusions & Inferences There are age‐related reductions in nerve fiber density in human colon circular muscle. NOS and VIP do not show regional variations, while SP nerve fiber density is higher in distal colon. 1/3 of pediatric STC patients have low SP or VIP nerve fiber density in proximal colon.     

Pacritinib (SB1518), a JAK2/FLT3 inhibitor for the treatment of acute myeloid leukemia

FMS-like tyrosine kinase 3 (FLT3) is the most commonly mutated gene found in acute myeloid leukemia (AML) patients and its activating mutations have been proven to be a negative prognostic marker for clinical outcome. Pacritinib (SB1518) is a tyrosine kinase inhibitor (TKI) with equipotent activity against FLT3 (IC₅₀=22 n) and Janus kinase 2 (JAK2, IC₅₀=23 n). Pacritinib inhibits FLT3 phosphorylation and downstream STAT, MAPK and PI3 K signaling in FLT3-internal-tandem duplication (ITD), FLT3-wt cells and primary AML blast cells. Oral administration of pacritinib in murine models of FLT3-ITD-driven AML led to significant inhibition of primary tumor growth and lung metastasis. Upregulation of JAK2 in FLT3-TKI-resistant AML cells was identified as a potential mechanism of resistance to selective FLT3 inhibition. This resistance could be overcome by the combined FLT3 and JAK2 activities of pacritinib in this cellular model. Our findings provide a rationale for the clinical evaluation of pacritinib in AML including patients resistant to FLT3-TKI therapy.     

Postnatal weight gain modifies severity and functional outcome of oxygen-induced proliferative retinopathy

In clinical studies, postnatal weight gain is strongly associated with retinopathy of prematurity (ROP). However, animal studies are needed to investigate the pathophysiological mechanisms of how postnatal weight gain affects the severity of ROP. In the present study, we identify nutritional supply as one potent parameter that affects the extent of retinopathy in mice with identical birth weights and the same genetic background. Wild-type pups with poor postnatal nutrition and poor weight gain (PWG) exhibit a remarkably prolonged phase of retinopathy compared to medium weight gain or extensive weight gain pups. A high (r(2) = 0.83) parabolic association between postnatal weight gain and oxygen-induced retinopathy severity is observed, as is a significantly prolonged phase of proliferative retinopathy in PWG pups (20 days) compared with extensive weight gain pups (6 days). The extended retinopathy is concomitant with prolonged overexpression of retinal vascular endothelial growth factor in PWG pups. Importantly, PWG pups show low serum levels of nonfasting glucose, insulin, and insulin-like growth factor-1 as well as high levels of ghrelin in the early postoxygen-induced retinopathy phase, a combination indicative of poor metabolic supply. These differences translate into visual deficits in adult PWG mice, as demonstrated by impaired bipolar and proximal neuronal function. Together, these results provide evidence for a pathophysiological correlation between poor postnatal nutritional supply, slow weight gain, prolonged retinal vascular endothelial growth factor overexpression, protracted retinopathy, and reduced final visual outcome.     

Laser ablation of foetal microcystic lung lesion: successful outcome and rationale for its use

OBJECTIVE: A foetus with an echodense, microcystic lung lesion complicated by non-immune hydrops has a high mortality rate. Because of the limited treatment options available, laser ablation was offered in an attempt to reduce the size of the lesion and reduce hydrops fetalis. METHODS AND RESULTS: A 25-year-old nulliparous woman presented at 21 weeks gestation. Ultrasound revealed a male foetus with a large microcystic right sided lung lesion that completely occupied the right hemithorax causing marked mediastinal deviation. The foetus was hydropic with polyhydramnios. Percutaneous laser ablation of the large microcystic lung lesion was performed under direct ultrasound control. At a power setting of 45 W, and using a 400 microm Nd:YAG laser fibre, the core of the lesion was photocoagulated in pulses lasting 5 s at 5 s intervals. The total target dose was 1683 J. This led to a marked but temporary reduction in amniotic fluid volume. The patient was commenced on sulindac and amniodrainage was performed at 27 weeks as reaccumulation of the polyhydramnios occurred. Pre-eclampsia complicated the pregnancy at 38 weeks gestation and an emergency caesarean section was performed. The baby underwent a thoracotomy and lobectomy at 48 h of age, made a good recovery, and is currently well 8 weeks post-delivery. CONCLUSIONS: In cases of cystic lung lesion complicated by hydrops, laser ablation should be considered as a treatment option.