Pleiotropy in Coffin-Lowry syndrome: Sensorineural hearing deficit and premature tooth loss as early manifestations

We report on 7 patients (6 M, 1 F) with Coffin-Lowry syndrome who have a sensorineural hearing deficit in addition to developmental delay and characteristic facial changes. One of the patients also had a history of premature exfoliation of primary teeth. These are previously unappreciated clinical signs that may aid in the early diagnosis of Coffin-Lowry syndrome. Early diagnosis and recognition of a hearing deficit in the patient can lead to the use of hearing aids to help the patient achieve his or her full potential. These “;new”; clinical manifestations expand the phenotype of Coffin-Lowry syndrome and constitute an additional indication of pleiotropy. © 1993 Wiley-Liss, Inc.     

Comfort of fenestrated hydrogel lenses

A controlled, double-masked, randomized study was conducted on ten subjects to determine the effect of fenestration size on the initial comfort of hydrogel contact lenses. Four fenestrated lenses were tested, each lens containing four mid-peripheral fenestrations of the same size. The diameter of the fenestrations used in the four lenses ranged from 0.39 to 0.96 mm. An unfenestrated lens was also tested. All lenses were made of HEMA and were ordered with the following specifications: -3.00 D, 14.0 mm diameter, 8.4 mm back central optic radius and 0.06 mm centre thickness. There was a significant negative correlation between comfort and fenestration size, indicating that larger fenestrations are less comfortable. Even the lens with the smallest fenestrations (0.39 mm) was significantly less comfortable than the unfenestrated lens. The implication of this finding is that fenestrations may not be clinically efficacious in view of the poor comfort (and presumably increased mechanical effect of the fenestration edges on the tarsal conjunctiva) of fenestrated lenses.     

Effects of arginine vasopressin (AVP) infusions on circulating concentrations of platelet AVP, factor VIII: C and von Willebrand factor

To study the possible role of arginine vasopressin (AVP) in the control of haemostasis AVP infusions at 3 doses (0.1, 0.2 and 0.3 mU/kg/min) were performed in 6 male volunteers. Both plasma and platelet AVP concentrations rose in a dose-related manner. At doses of 0.2 and 0.3 mU/kg/min there was an increase in the plasma concentrations of both plasma Factor VIII and von Willebrand factor. The data support the hypothesis that AVP, by interacting with platelets and stimulating factor VIII and von Willebrand factor release, plays a role in the control of haemostasis.     

The cost-effectiveness of newer drugs as add-on therapy for children with focal epilepsies.

PURPOSE: Epilepsies in children are complex diseases. Guidelines are needed on the appropriate use of newer versus older anti-epileptic drugs (AEDs). This paper presents an individual patient-sampling model to assess the cost-effectiveness of using newer AEDs as add-on therapy in line with UK prescribing guidance. METHODS: Identification of the relevant parameters and treatment pathways for the model were achieved by a systematic review of the literature and discussions with clinical experts. Data were obtained from the literature and supplemented with data elicited from paediatric neurologists. The model considered paediatric patients over the period of childhood from the age of diagnosis to 18 years. RESULTS: The results suggest that the older and newer AEDs are similar in terms of drug retention rates and the average time in 'good' treatment outcomes. In terms of cost, the results indicate a consistent increase in cost (compared to older AEDs) when all of the newer AEDs are considered. The decision analysis results indicate that there are no important health benefits from the use of newer AEDs when used as add-on therapy. However, the analysis also reveals that the uncertainties in the model are greater than the differences between the drug strategies. CONCLUSIONS: To develop guidelines on the appropriate use of newer AEDs, better information is required from randomised controlled trials as there is insufficient data available in the public domain to accurately estimate the nature of the trade off between older versus newer AEDs.     

Auditory steady-state evoked potentials (ASSEPs): a study of optimal stimulation parameters for frequency-specific threshold measurement in dogs.

OBJECTIVE: To define the optimal stimulation parameters (AM/FM vs AM alone and modulation rate) for frequency-specific threshold measurements using ASSEPs in dogs. Dependent variables were thresholds and recording times needed to obtain a response at threshold. To compare the ASSEP threshold results obtained with the optimal stimulation parameters to those obtained with the Tone-Burst/Auditory Brainstem Response (TB/ABR) combination. METHODS: Thirty-two sedated Beagle puppies were tested at 5 audiometric frequencies (0.5-8 kHz) and 6 ASSEP modulation rates (21-199 Hz). RESULTS: The ASSEP threshold-modulation rate functions had a high-pass profile with corner frequencies of 101 Hz for 0.5, 1 and 2 kHz carriers and of 151 Hz for 4 and 8 kHz carriers. AM stimuli did not yield higher thresholds than the AM/FM ones except at 1 kHz. Modulation type had no effect on testing duration. Audiometric profiles were obtained much more rapidly with ASSEPs than with TB/ABRs (mean: 50 vs 135 min). Both ASSEP and TB/ABR provided thresholds estimates characterized by low intersubject variability. CONCLUSIONS: ASSEPs are a valid and rapid method for audiometric assessment in sedated dogs. SIGNIFICANCE: ASSEPs offer a new, competitive tool for frequency-specific assessment of hearing in the canine species.     

Angiopoietin1/Tie2 and VEGF/Flk1 induced by MSC treatment amplifies angiogenesis and vascular stabilization after stroke.

Bone marrow stromal cells (MSCs) increase vascular endothelial growth factor (VEGF) expression and promote angiogenesis after stroke. Angiopoietin-1 (Ang1) and its receptor Tie2 mediate vascular integrity and angiogenesis as does VEGF and its receptors. In this study, we tested whether MSC treatment of stroke increases Ang1/Tie2 expression, and whether Ang1/Tie2 with VEGF/ vascular endothelial growth factor receptor 2 (VEGFR2) (Flk1), in combination, induced by MSCs enhances angiogenesis and vascular integrity. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAo) and treated with or without MSCs. Marrow stromal cell treatment significantly decreased blood-brain barrier (BBB) leakage and increased Ang1, Tie2, and occludin (a tight junction protein) expression in the ischemic border compared with MCAo control. To further test the mechanisms of MSC-induced angiogenesis and vascular stabilization, cocultures of MSCs with mouse brain endothelial cells (MBECs) or astrocytes were performed. Supernatant derived from MSCs cocultured with MBECs significantly increased MBEC expression of Ang1/Tie2 and Flk1 compared with MBEC alone. Marrow stromal cells cocultured with astrocytes also significantly increased astrocyte VEGF and Ang1/Tie2 expression compared with astrocyte culture alone. Conditioned media from MSCs alone, and media from cocultures of MSCs with astrocytes or MBECs, all significantly increased capillary tube-like formation of MBEC compared with control Dulbecco's modified Eagle's medium media. Inhibition of Flk1 and/or Ang1 significantly decreased MSC-induced MBEC tube formation. Knockdown of Tie2 expression in MBECs significantly inhibited MSC-induced tube formation. Our data indicate MSC treatment of stroke promotes angiogenesis and vascular stabilization, which is at least partially mediated by VEGF/Flk1 and Ang1/Tie2.