Germline mutations in the neurofibromatosis type 2 tumour suppressor gene

The recent identification of the NF2 tumour suppressor genehas enabled large scale screening for pathological mutationsin the gene. We have sought germline mutations In the NF2 geneby SSCP and heteroduplex analysis of cDNA and genomic DNA samplesfollowed by cloning and sequencing of mutant alleles. In thepresent report we describe 11 putative pathological mutations,including five nonsense mutations, three short insertions ordeletions cauing frameshifts and three missense mutations. Moststop mutations and frameshift mutations were found In Individualsexpressing a severe phenotype while one of the three missensemutations was associated with a mild phenotype. Four unrelatedNF2 patients of the 93 tested were found to have identical nonsensemutations caused by a C to T transition (C169) in a CpG dinucleotide,which is a potential mutational hotspot in the NF2 tumour suppressorgene.     

Effects of preparation techniques on the porosity of acrylic cements

We investigated four acrylic cement preparation techniques for their effects on cement porosity: hand mixing, pressurization in a pneumatic pistol, centrifugation, and vacuum mixing. All the techniques were tested on three types of cement with different viscosity characteristics. The best results were obtained with vacuum mixing using a newly designed experimental system, yielding porosity reductions of 60-80 percent relative to hand mixing. Vacuum mixing with a commercial system was also effective, but to a somewhat lesser extent.

Pressurization and centrifugation had no substantial effect on the overall porosity. Centrifugation led to considerable nonuniformity in the distribution of pores and additives.     

Short utterance recognition using a network with minimum training

A feedforward network is used to recognize short, digitized, isolated utterances. A high, multispeaker recognition rate is achieved with a small vocabulary with a single training utterance. This approach makes use of the pattern recognition property of the network architecture to classify different temporal patterns in the multidimensional feature space. The network recognizes the utterances without the need of segmentation, phoneme identification, or time alignment. We train the network with four words spoken by one single speaker. The network is then able to recognize 20 tokens spoken by 5 other speakers. We repeat the above training and testing procedure using a different speaker's utterances for training each time. The overall accuracy is 97.5%. We compare this approach to the traditional dynamic programming (DP) approach, and find that DP with slope constraints of 0 and 1 achieve 98.5% and 85% accuracies respectively. Finally we validate out statistics by training and testing the network of a four-word subset of the Texas Instruments (Tl) isolated word database. The accuracy with this vocabulary exceeds 96%. By doubling the size of the training set, the accuracy is raised to 98%. Using a suitable threshold, we are able to raise the accuracy of one network from 87% to 98.5%. Thresholding applied to all networks would then raise the overall accuracy to well over 99%.

This technique is especially promising because of the low overhead and computational requirements, which make it suitable for a low cost, portable, command recognition type of application.     

Raman and UV–vis spectroscopic study of polyaniline membranes containing a bulky cationic additive

Electrically conducting soluble polyaniline (PANI), containing different amounts of a bulky lipophilic cationic additive, tridodecylmethylammonium chloride (TDMACl), was studied by Raman (λ_exc=780 nm) and UV–vis spectroscopy. PANI was made simultaneously electrically conducting and soluble with bis[4-(1,1,3,3-tetramethylbutyl)phenyl]phosphoric acid in dichloromethane. The PANI membranes were prepared by drop casting on glassy carbon or ITO substrates. Raman and UV–vis measurements were carried out in a 0.1 M CaCl₂ solution at potentials between 400 and ?600 mV (vs. SCE) at pH 6, or alternatively at the open circuit potential at pH 10. The results of Raman, UV–vis and cyclic voltammetric measurements confirm that the incorporation of TDMACl into the PANI membrane facilitates the oxidation and reduction of PANI.     

Intracapsular tonsillar reduction (partial tonsillectomy): reviving a historical procedure for obstructive sleep disordered breathing in children.

OBJECTIVE: We sought to reintroduce a historical procedure-intracapsular tonsillar reduction (partial tonsillectomy or tonsillotomy)-for tonsillar hypertrophy causing obstructive sleep disordered breathing (OSDB) in children, as well as to determine whether partial tonsillectomy, compared with conventional (total) tonsillectomy when performed by more than one surgeon, is equally effective for the relief of OSDB while resulting in less pain and more rapid recovery. STUDY DESIGN: We conducted a retrospective case series at a tertiary children's hospital. The charts of children who underwent partial tonsillectomy and total tonsillectomy (1998 through 2002) for postoperative complications were reviewed. The caregivers were surveyed to assess postoperative pain, rapidity of recovery, and effectiveness of surgery for relieving symptoms of OSDB. RESULTS: Two hundred forty-three children underwent partial tonsillectomy and 107 children underwent total tonsillectomy. There were no significant differences in immediate and delayed complications between the groups. Both operations were equally effective in relieving OSDB. Children who had partial tonsillectomy had significantly less postoperative pain and significantly more rapid recovery. CONCLUSION: Intracapsular tonsillar reduction with an endoscopic microdebrider relieves OSDB as effectively as conventional tonsillectomy, but results in less postoperative pain and a more rapid recovery.     

Postprandial acid reflux is reduced by delayed gastric emptying.

The aim of this study was to investigate influence of delayed gastric emptying on postprandial reflux in esophageal pH. Sixty-nine consecutive patients underwent 24 hour (h) esophageal pH monitoring and gastric emptying. In 24 h esophageal pH monitoring, % postprandial reflux pH<4 for 2 h after each meal (% PRT) was extracted from the 24 h pH profile. After solid test meal (1 mCi, Tc99m) was given, gastric emptying was measured with a gamma detector placed transnasally 5 cm below lower esophageal sphincter. % PRT was similar among the 34 normal, 26 delayed and 9 rapid gastric emptying rate patients. Thirty-five with a positive pH study and 34 with a negative had a similar prevalence of gastric emptying disorder. In the positive pH study group, patients with normal gastric emptying had significantly higher % PRT than those with delayed gastric emptying (22.0 vs 12.1%, P<0.05). In the same population, patients with a normal %PRT had a significantly higher prevalence of delayed gastric emptying compared with those with a positive % PRT (6/8 vs 9/27, P<0.05). In patient with abnormal acid exposure but normal % PRT on 24 h esophageal pH monitoring, gastric emptying may be delayed.     

Novel pore mutation in SCN5A manifests as a spectrum of phenotypes ranging from atrial flutter, conduction disease, and Brugada syndrome to sudden cardiac death

OBJECTIVES: The purpose of this study was to determine the clinical and biophysical characteristics of a novel SCN5A mutation. BACKGROUND: Brugada syndrome and isolated cardiac conduction defect have been linked to SCN5A mutations. METHODS: Eleven members of a western European family underwent electrophysiologic investigations and mutation analysis of the SCN5A gene. Wild-type and mutant SCN5A channels were expressed in HEK293 cells, and whole cell currents were studied using patch clamp procedures. RESULTS: A novel mutation, R376H, in the first pore segment of SCN5A variably causes Brugada syndrome and/or conduction disease in a single family. Biophysical analysis demonstrated a significant current reduction for the mutant, a pathophysiologic profile consistent with Brugada syndrome and isolated cardiac conduction defect. Among 11 family members, 9 were carriers of the mutation. The proband's initial presentation was a saddleback Brugada ECG, atrial flutter, and diffuse conduction disturbances. He had no inducible ventricular arrhythmias but experienced sudden cardiac death. His brother was affected by atrial flutter and had a clear conduction disorder, but he did not display baseline or evocable ECG signs of Brugada syndrome. He received an implantable cardioverter-defibrillator that delivered one appropriate shock after 1 year of follow-up. The phenotype in the family members was highly variable and ranged from noninducible and inducible asymptomatic carriers of the mutations to isolated conduction disease and to symptomatic Brugada syndrome. CONCLUSIONS: We describe the functional characterization of a novel SCN5A pore mutation, R376H, with variable clinical expression in the same family. Differentiating between electrophysiologic entities (Brugada syndrome-isolated cardiac conduction defect) is more challenging. Recognition of factors modifying the clinical presentation may be important for clinical decision making.     

Giving patients an audiotape of their GP consultation: a randomised controlled trial.

BACKGROUND: Providing patients with an audiotape of their medical consultation has been a relatively common practice in oncology clinics for some years. However, broader generalisability of the technique has yet to be examined. AIMS: To investigate the efficacy of providing patients with an audiotape of their consultation in a general practice setting. DESIGN OF STUDY: Randomised controlled trial: 95 experimental participants, 85 controls. SETTING: Routine surgeries run by two general practitioners (GPs) in two different health centres. METHOD: All patients attending GP appointments were eligible for inclusion. Patients were followed up by telephone 7-10 days later. RESULTS: More than half (61%) of the patients who received a tape listened to it. Among listeners, 64% rated the tape useful or very useful; 24% noticed information not heard in the consultation. Half of listeners (46%) said that their understanding of the consultation improved after listening to the tape. Half of the listeners (48%) shared the tape with others, of whom 71% found sharing helpful or very helpful. However, 21% of those who shared the information with others found this unhelpful or very unhelpful, suggesting that patients may need to be briefed on the potential risks of sharing. At follow-up a week later, it emerged that being given a tape had no effect on adherence with GPs' advice, nor on anxiety about conditions. CONCLUSION: Providing patients with an audiotape of their GP consultation was positively rated by many patients. Although there were no detectable clinical effects at follow-up, the technique merits further evaluation in general practice.