Co-localization of choline acetyltransferase and tyrosine hydroxylase within neurons of the dorsal motor nucleus of the vagus

In the present study, we employed a dual-immunofluorescent labeling procedure to determine if the biosynthetic enzymes tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) are co-localized within neurons in the dorsal medulla of rat. Within this region TH-labeled neurons are distributed within the nuclei of the solitary tracts and medial aspect of the dorsal motor nucleus of the vagus. The absence of dopamine-beta-hydroxylase immunoreactivity within TH-labeled cells in the medial portion of the dorsal motor nucleus of the vagus suggests that these neurons are dopaminergic. Cholinergic perikarya also are present in the dorsal medulla and are distributed throughout the dorsal motor nucleus of the vagus and hypoglossal nucleus. Of these ChAT-positive perikarya, a small percentage limited to the medial aspect of the dorsal motor nucleus of the vagus (i.e., corresponding to the location of dopamine neurons) also contain TH. The existence of TH within ChAT-positive neurons in the dorsal motor nucleus of the vagus provides an anatomical substrate with which to suggest that catecholaminergic and cholinergic fibers contribute to the vagus nerve and may serve to explain some of the cardiac and gastric effects resulting from systemic administration of catecholamine agents.     

Early treatment benefits of ropinirole prolonged release in Parkinson's disease patients with motor fluctuations

We performed a retrospective analysis of the Efficacy And Safety Evaluation in Parkinson's Disease (EASE‐PD) Adjunct Study, assessing the minimum time to symptom improvement after initiation of ropinirole prolonged release (2–24 mg/day) versus placebo in patients with moderate‐to‐advanced PD not optimally controlled with levodopa. Ropinirole prolonged release was superior to placebo at Week 2 for change from baseline in “off” time (adjusted mean treatment difference [AMTD] – 0.7 hours; 95% confidence interval [CI], –1.1, –0.2; P = 0.0029), and “on” time without troublesome dyskinesia (0.4 hours; 95%CI, 0.01, 0.88; P = 0.0444). At Week 4, improvements were seen in change from baseline in Unified Parkinson's Disease Rating Scale total motor score (AMTD, –3.1; 95%CI, –4.4, –1.8; P < 0.0001), activities of daily living score (AMTD, –1.1; 95%CI, –1.7, –0.5; P = 0.0004), and the cardinal symptoms of PD compared with placebo. These analyses indicate that once‐daily, adjunctive ropinirole prolonged release can offer PD symptom control 2 weeks after treatment initiation. © 2010 Movement Disorder Society     

Teflon radiolysis as the major source of carrier in fluorine‐18

The practical upper limit of fluorine‐18 specific activity has remained constant for many years among cyclotron facilities internationally. Although there have been isolated reports of very high specific activity and hints concerning the sources of carrier, experiments designed to identify carrier sources have been inconclusive and largely ineffective. This report describes experiments to test the hypothesis that radiolysis of fluorinated components is a source of carrier fluoride. Controlled experiments were performed in which contributions of irradiated fluorinated components to the mass of synthesized [¹⁸F]fluorobenzaldehyde (FBA) were measured. There was clear correlation between irradiation of Teflon and carrier mass. There was an additive effect of carrier due to different fluoropolymer components. It was concluded that in typical target and radiosynthesis systems it is radiolysis of fluorinated material and not the material itself that generates a large majority of the carrier typically reported. All Teflon and other fluorinated materials in contact with the [¹⁸F]fluoride solution were removed. With no further efforts to reduce carrier fluoride, FBA produced from a modest irradiation attained a reduction in mass from over 500 nmol to 30 nmol, and an increase in specific activity from 0.1 TBq (3 Ci) to 1.9 TBq (51 Ci) per micromole. Copyright © 2009 John Wiley & Sons, Ltd.     

Segmental basal cell naevus syndrome caused by an activating mutation in smoothened

Aberrant sonic hedgehog signalling, mostly due to PTCH1 mutations, has been shown to play a central role in the pathogenesis of basal cell carcinoma (BCC), as well as in basal cell naevus syndrome (BCNS). Mutations in smoothened (SMO) encoding a receptor for sonic hedgehog have been reported in sporadic BCCs but not in BCNS. We report a case with multiple BCCs, pits and comedones in a segmental distribution over the upper part of the body, along with other findings compatible with BCNS. Histopathologically, there were different types of BCC. A heterozygous mutation (c.1234C>T, p.L412F) in SMO was detected in three BCCs but not in peripheral blood lymphocytes or the uninvolved skin. These were compatible with the type 1 mosaic form of BCNS. The p.L412F mutation was found experimentally to result in increased SMO transactivating activity, and the patient responded to vismodegib therapy. Activating mutations in SMO may cause BCNS. The identification of a gain‐of‐function mutation in SMO causing a type 1 mosaic form of BCNS further expands our understanding of the pathogenesis of BCC, with implications for the treatment of these tumours, whether sporadic or inherited.     

Computed tomography of the head in the evaluation of microcephaly

Eighty-five infants and children found to have microcephaly had computed tomographic (CT) brain scans performed. A greater degree of microcephaly correlated with the finding of atrophy or ventricular dilation on CT scan. Patients who had known preceding destructive brain insults had the highest incidence of abnormal findings on scans (20/22). Patients who had CNS dysfunction of unknown etiology had the lowest frequency of abnormal findings (12/33); however, in three of these patients, a previously unsuspected brain malformation was found on CT scan. Patients who had other congenital anomalies had an intermediate proportion of abnormal findings on CT scans (20/30), and in 11 of these scans, a previously unsuspected or only partly suspected brain malformation was diagnosed. Discovering previously unsuspected information or finding supportive data regarding the basis for the underlying disease process, being able to provide a more specific developmental prognosis and accurate genetic counseling, justifies the inclusion of a CT scan of the head in the evaluation of the microcephalic child.