PET of Brain Prion Protein Amyloid in Gerstmann–Sträussler–Scheinker Disease

In vivo amyloid PET imaging was carried out on six symptomatic and asymptomatic carriers of PRNP mutations associated with the Gerstmann–Sträussler–Scheinker (GSS) disease, a rare familial neurodegenerative brain disorder demonstrating prion amyloid neuropathology, using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP). 2-Deoxy-2-[F-18]fluoro-d -glucose PET ([F-18]FDG) and magnetic resonance imaging (MRI) scans were also performed in each subject. Increased [F-18]FDDNP binding was detectable in cerebellum, neocortex and subcortical areas of all symptomatic gene carriers in close association with the experienced clinical symptoms. Parallel glucose metabolism ([F-18]FDG) reduction was observed in neocortex, basal ganglia and/or thalamus, which supports the close relationship between [F-18]FDDNP binding and neuronal dysfunction. Two asymptomatic gene carriers displayed no cortical [F-18]FDDNP binding, yet progressive [F-18]FDDNP retention in caudate nucleus and thalamus was seen at 1- and 2-year follow-up in the older asymptomatic subject. In vitro FDDNP labeling experiments on brain tissue specimens from deceased GSS subjects not participating in the in vivo studies indicated that in vivo accumulation of [F-18]FDDNP in subcortical structures, neocortices and cerebellum closely related to the distribution of prion protein pathology. These results demonstrate the feasibility of detecting prion protein accumulation in living patients with [F-18]FDDNP PET, and suggest an opportunity for its application to follow disease progression and monitor therapeutic interventions.     

Resuscitation of depressed newborn infants with ambient air or pure oxygen: a meta-analysis

BACKGROUND: It is discussed whether depressed newborn infants should be resuscitated with room air or 100% O2. OBJECTIVE: To perform a systematic review and meta-analysis including studies that report resuscitation of depressed newly born infants with 21 or 100% O2. METHODS: Inclusion criterion was randomized or pseudo-randomized, blinded or not, studies of depressed newborn infants resuscitated with either 21 or 100% O2. The literature was searched in Medline/Pubmed/EMBASE and The Cochrane library databases. All identified studies were included. RESULTS: Five studies fulfilled the inclusion criterion in which 881 infants were resuscitated with 21% O2 and 856 with 100% O2. Neonatal mortality was 8.0 vs. 13.0% in the 21 and 100% O2 groups respectively, OR 0.57, 95% CI 0.42-0.78. In term infants neonatal mortality was 5.9% in the 21% O2 group and 9.8% in the 100% O2 group, OR 0.59, 95% CI 0.40-0.87. The figures for the premature infants were very similar. In infants with 1-min Apgar score <4, OR for neonatal mortality was 0.81 (95% CI 0.54-1.21). Apgar score at 5 min and heart rate at 90 s were significantly higher, and time to first breath significantly earlier in infants given 21% O2 compared with 100% O2. CONCLUSIONS: A systematic review and meta-analysis demonstrated that neonatal mortality is significantly reduced when depressed newly born infants are resuscitated with ambient air instead of pure oxygen. For infants with low 1-min Apgar score (<4), no significant difference in neonatal mortality was found. Recovery was faster in infants resuscitated with 21% O2 than 100% O2.     

Pre and post eradication gastric inflammation in Helicobacter pylori-associated duodenal ulcer.

BACKGROUND: Distribution and nature of gastritis are major determinants of clinical outcome of H. pylori infection. The gastric inflammatory changes associated with this infection in developing countries have not been systematically studied. AIMS: To evaluate the inflammatory changes in gastric antrum and corpus in patients with duodenal ulcer and H. pylori infection, before and after H. pylori eradication therapy. METHODS: Histology and H. pylori density were studied in gastric biopsies obtained from 53 consecutive patients with active duodenal ulcer and H. pylori infection. Biopsies were obtained before and 4 weeks after H. pylori eradication therapy, from the anterior and posterior walls of the antrum and corpus, and were evaluated according to the Sydney system. RESULTS: In the pre-H. py/ori eradication antral biopsies, chronic gastritis, active gastritis, atrophy, intestinal metaplasia (IM) and lymphoid follicles / aggregates were seen in 53 (100%), 49 (92%), 11 (21%), 7 (13%) and 28 (53%) patients, respectively. In the corresponding biopsies from gastric corpus, these changes were seen in 49 (92%), 23 (43%), 2 (4%), 2 (4%) and 8 (15%), respectively. All changes except IM were significantly more frequent and of higher grade in the antrum. The grade of chronic gastritis was significantly higher in antrum than corpus; the frequency of gastritis in the antrum and corpus was similar (100% vs. 92%). H. pylori density was also higher in the antrum and correlated well with the grades of chronic gastritis and activity at both sites. Eradication of H. pylori was achieved in 39 patients (74%), and led to significant decrease in gastritis; no change was seen in patients who did not eradicate the organism. CONCLUSIONS: Antral-predominant chronic gastritis and activity are present in more than 90% of patients with H. pylori infection associated with duodenal ulcer, and the grade of gastritis correlates with the density of the organism. Eradication therapy results in improvement of both chronic gastritis and activity.     

Preclinical activity of the novel B‐cell‐specific Moloney murine leukemia virus integration site 1 inhibitor PTC‐209 in acute myeloid leukemia: Implications for leukemia therapy

Curing patients with acute myeloid leukemia (AML) remains a therapeutic challenge. The polycomb complex protein B‐cell‐specific Moloney murine leukemia virus integration site 1 (BMI‐1) is required for the self‐renewal and maintenance of leukemia stem cells. We investigated the prognostic significance of BMI‐1 in AML and the effects of a novel small molecule selective inhibitor of BMI‐1, PTC‐209. BMI‐1 protein expression was determined in 511 newly diagnosed AML patients together with 207 other proteins using reverse‐phase protein array technology. Patients with unfavorable cytogenetics according to Southwest Oncology Group criteria had higher levels of BMI‐1 compared to those with favorable (P = 0.0006) or intermediate cytogenetics (P = 0.0061), and patients with higher levels of BMI‐1 had worse overall survival (55.3 weeks vs. 42.8 weeks, P = 0.046). Treatment with PTC‐209 reduced protein level of BMI‐1 and its downstream target mono‐ubiquitinated histone H2A and triggered several molecular events consistent with the induction of apoptosis, this is, loss of mitochondrial membrane potential, caspase‐3 cleavage, BAX activation, and phosphatidylserine externalization. PTC‐209 induced apoptosis in patient‐derived CD34⁺ CD38^low/− AML cells and, less prominently, in CD34⁻ differentiated AML cells. BMI‐1 reduction by PTC‐209 directly correlated with apoptosis induction in CD34⁺ primary AML cells (r = 0.71, P = 0.022). However, basal BMI‐1 expression was not a determinant of AML sensitivity. BMI‐1 inhibition, which targets a primitive AML cell population, might offer a novel therapeutic strategy for AML.     

Anterior spinal artery syndrome in a 16-year-old male

Spinal cord infarction is a relatively uncommon condition in young children and adolescents, however, it should be included in the differential diagnosis of acute cord compression. Depending on the vessel involved, the clinical presentation may differ. The degree of recovery in spinal cord infarcts varies from one individual to another. Recovery of motor function is progressive in most of the patients, with the deficit being maximal at the onset. For successful outcome, it is imperative that these patients get access to approriate rehabilitation very early in the course of the disease. Prevention and early treatment of specific complications, especially chronic pain, is of vital importance in young patients. This article describes our experiences diagnosing and treating a 16-year-old boy with anterior spinal artery syndrome.