A pilot study to explore the experiences of congenitally or early profoundly deafened candidates who receive cochlear implants as adults.

OBJECTIVES: To explore the experiences of congenitally or early profoundly deafened candidates who receive cochlear implants as adults. METHODS: Eight congenitally or early profoundly deafened implantees who had received their implants as adults were interviewed using a semi-structured interview technique. Interviews were conducted in the participant's preferred communication mode (oral/aural, Sign Supported English, or British Sign Language). RESULTS: All participants reported benefit from implantation. Areas of benefit identified correspond with results from similar studies conducted with post-lingually deafened adult implantees. DISCUSSION: Congenitally or early profoundly deafened adults implanted as adults report benefit from cochlear implantation in the following areas: identity, hearing the world, and emotional wellbeing. They also commented on their motivation for wanting an implant and the advice they would give to others considering implantation.

Psychotic features in chronic posttraumatic stress disorder and schizophrenia: comparative severity.

Psychotic features are frequent in combat veterans with chronic posttraumatic stress disorder (PTSD), may correlate with severity of PTSD symptoms, and may reflect a distinct subtype of the disorder. These psychotic features include auditory and visual hallucinations and delusional thinking that is usually paranoid in nature. Psychotic features may be under-recognized in chronic PTSD because patients are reluctant to report these symptoms and because they may not have overt changes in affect or bizarre delusions characteristic of other psychoses, e.g., schizophrenia. To further assess these phenomena, we compared clinical ratings on the Positive and Negative Syndrome Scale (PANSS) and other assessments, including the Clinical Global Impression Scale and the Structured Clinical Interview with Psychotic Screen, in veterans meeting DSM-IV criteria for chronic PTSD with well-defined comorbid psychotic features (N = 40) or chronic schizophrenia (N = 40). The patients with schizophrenia had modestly higher composite PANSS scores and positive symptom scores although average scores in both groups were moderate to severe in intensity. Negative symptom and general psychopathology subscale scores were comparable in both groups. Regarding specific positive symptoms, hallucinations were comparable between groups in severity; however, schizophrenia patients had slightly more intense delusions and conceptual disorganization. These data further validate the occurrence of positive as well as negative symptoms of psychosis in chronic PTSD in a range of severity that may approach that of patients with schizophrenia. Although meeting DSM-IV criteria for two different major psychiatric disorders, these two patient populations were remarkably similar with respect to not only positive but also negative symptoms.

Immunity induced by DNA immunization with herpes simplex virus type 2 glycoproteins B and C.

The complete sequence of herpes simplex virus type 2 (HSV-2) glycoproteins B and C (gB & gC) were cloned into plasmid expression vectors and evaluated in murine and guinea pig genital HSV-2 models. Balb/c mice were immunized with either pgB-2 or pgC-2 plasmids intramuscularly (IM) or intradermally (ID). The vaccines induced HSV-2-specific neutralizing and ELISA IgG antibody, but little or no enhancement of viral clearance from the vagina was detected following intravaginal challenge. Immunization of guinea pigs with pgB-2 or pgC-2 induced ELISA IgG antibody; however, antibody titers were approximately one log(10) unit lower than that seen in HSV-2 convalescent sera. IM immunization of guinea pigs with either plasmid also did not decrease vaginal viral shedding following vaginal challenge, but the severity of the acute disease and the subsequent number of recurrent lesion days were reduced in animals immunized with pgB-2. Lastly, IM immunization of latently infected guinea pigs with a combined gB-2 and gC-2 plasmid vaccine significantly reduced the number of subsequent HSV-2 recurrences. DNA vectors expressing gB-2 or gC-2 were both immunogenic, although the gB-2 plasmid induced higher titers of antibody and significantly reduced primary and recurrent herpetic disease in the guinea pig model. These results also suggest that immunotherapy with plasmid expression vectors may be effective against recurrent genital HSV-2 disease.

Electrode and device problems: manifestation and management.

A total of 119 children were implanted with the Nucleus 22 implant on the Nottingham program by March 1996. Twenty-five (i.e. 21%) of these had an electrophysiologically confirmed fault on at least 1 channel and 6 (i.e. 5%) had experienced total device failure. How these problems were first manifested and what the subsequent effects were on the child and family were determined by means of questionnaires and detailed examination of clinical notes. Our findings indicated that 76% of all internal device faults were initially detected in tuning or electrophysiological measurement. All parents expressed deep anxiety about the threat of device failure; cases of total failure occurring over a long period of time resulted in the greatest distress and effect on the family. Recommendations are made for companies to assist clinics in minimizing such effects.

Intraoperative electrophysiological and objective tests after cochlear re-implantation in a young child.

The electrically evoked auditory brainstem response (EABR) and stapedius reflex threshold (ESRT) are routinely recorded during implant surgery with the Nucleus 22 channel cochlear implant in the Nottingham Paediatric Cochlear Implant Programme and are extremely valuable in the management of young implanted children. These intraoperative tests were carried out in a young child on the occasion of the first implantation and then after re-implantation 17 months later following malfunction of the first device. The surgical experiences of the first implantation and the re-implantation were both straightforward. Recordings of the intraoperative EABR and ESRT were typical of the expected pattern of responses on both occasions and there was only a small reduction in threshold sensitivity after re-implantation. These investigations provide valuable objective information to support and assist with the management of re-implantation in a young child.

Structure and immunogenicity of experimental foot-and-mouth disease and poliomyelitis vaccines.

The physico-chemical properties and immunogenicity of experimental vaccines against foot-and-mouth disease (FMD) and poliomyelitis, prepared by treatment of the viruses with N-acetylethyleneimine (AEI), formaldehyde or neutral red, have been studied. None of these reagents affects the rate of sedimentation of the particles or their reaction with antibody against the major immunogenic sites. FMD vaccines prepared by inactivation with AEI or neutral red, behaved like the untreated virus, in that they were disrupted on lowering the pH below 7. The RNA of the AEI-inactivated virus was degraded into slowly sedimenting molecules. Unlike AEI-inactivated virus, from which all the RNA could be extracted with phenol-SDS, the recovery from the neutral red inactivated virus was variable and was sometimes as low as 40%; this RNA gave a heterogenous profile in sucrose gradients. The capsid proteins in the AEI preparation migrated in SDS-PAGE to the same positions as those of untreated virus, but in the neutral red preparation there was evidence of cross-linking. In contrast, the formaldehyde-inactivated vaccine was stable below pH 7 and the RNA could not be released by extraction with phenol-SDS at pH 5, because the capsid proteins had become cross-linked and/or linked to the RNA. As with foot-and-mouth disease virus (FMDV), poliovirus which had been inactivated with formaldehyde did not release its RNA on extraction with phenol-SDS and the capsid proteins were also cross-linked. Surprisingly, although AEI cleaved the viral RNA slowly in situ, the virus was no longer infectious after 6 h. Neutral red did not reduce the infectivity of the virus. All of the preparations gave similar levels of neutralizing antibody after a single inoculation. The high levels obtained with the formaldehyde-inactivated vaccines have implications for the processing of fixed particles by the antigen-presenting cells.

The cellular C1 factor of the herpes simplex virus enhancer complex is a family of polypeptides.

The alpha/immediate early genes of herpes simplex virus are regulated by the specific assembly of a multiprotein enhancer complex containing the Oct-1 POU domain protein, the viral alpha-transinduction factor alpha TIF, (VP16, ICP25), and the C1 cellular factor. The C1 factor from mammalian cells is a heterogeneous but related set of polypeptides that interact directly with the alpha-transinduction factor to form a heteromeric protein complex. The isolation of cDNAs encoding the polypeptides of the C1 factor suggests that these proteins are proteolytic products of a novel precursor. The sequence of the amino termini of these polypeptide products indicate that the proteins are generated by site-specific cleavages within a reiterated 20-amino acid sequence. Although the C1 factor appears to be ubiquitously expressed, it is localized to subnuclear structures in specific cell types.

Characterization of an acid-resistant mutant of foot-and-mouth disease virus.

A foot-and-mouth disease virus mutant which is stable at pH 6.4 has been isolated from a virus of serotype A. In contrast to the parent (P) virus, which gave a mixture of large and small plaques in BHK21 cells and in a bovine kidney cell line, the acid-resistant (AR) virus gave small plaques which did not increase markedly in size after 24 hr. The infectivity titer of the acid-resistant virus was about 100-fold lower in suckling mice than in BHK21 cells, whether the inoculation was made intraperitoneally or intracerebrally, whereas the parent virus gave similar titers in both systems. Furthermore, in mice the AR virus reached its end point two to three times more slowly. The diameter of the AR virus was almost 20% less than that of the P virus and it had a more distinct topography, but the two viruses cosedimented in sucrose gradients. However, the buoyant density in CsCl of the AR virus was slightly lower (1.42 compared with 1.43 g/cc) in coruns. The RNAs and capsid proteins of the two viruses gave similar profiles in sucrose gradients and by SDS-PAGE, respectively. However, isoelectric focusing of the capsid proteins revealed considerable differences between the two viruses. Whereas the P virus gave four protein bands, corresponding to VP1-VP4, the AR virus gave one band for VP4, two for VP3, two for VP2, and four for VP1. Sequence analysis of the genes coding for the capsid protein regions of the two viruses showed four changes (one silent), resulting in an Ala-3-->Ser substitution in VP1 and Glu-131-->Lys and Asp-133-->Ser substitutions in VP2.

Clinical evaluation and test-retest reliability of the IHR-McCormick Automated Toy Discrimination Test.

The IHR-McCormick Automated Toy Discrimination Test (ATT) measures the minimum sound level at which a child can identify words presented in quiet in the sound field. This 'word-discrimination threshold' provides a direct measure of the ease with which a child can identify speech and a surrogate measure of auditory sensitivity. This paper describes steps taken to maximize the test-retest reliability of the ATT and to enable it to measure word-discrimination thresholds in noise as well as in quiet. It then describes the results of a clinical evaluation of the ATT in which paediatric audiologists measured word-discrimination thresholds in quiet from 215 successive attendees (in the age range 2 to 13 years) at a paediatric audiology clinic presenting over a 2-month period. When children with atypical cognition or delayed development of language were excluded, 72% of the children provided two word-discrimination thresholds and 83% provided at least one word-discrimination threshold. Children who failed to provide word-discrimination thresholds were generally younger than four years of age. Although a few children who could not perform pure-tone or warble-tone audiometry managed to provide word-discrimination thresholds, most children who could perform the ATT could also perform pure-tone audiometry. The average pure-tone threshold in the better-hearing ear could be predicted from the word-discrimination threshold with a 95% confidence interval of +/- 13 dB. The test-retest reliability of the ATT was measured in two ways. First, to enable comparison with published results, the within-subjects standard deviation of word-discrimination thresholds was calculated. It varied as a function of age and degree of impairment, but was never worse than 3.3 dB. Children of four years of age and older displayed the adult reliability of 2.3 dB. Second, the variability of absolute differences between word-discrimination thresholds was calculated. It was such that a change of 7 dB between two runs of the test (e.g. aided and unaided) would be expected to occur by change less than one time in 20. These results extend previous evaluations of the ATT to a clinically representative population and confirm that word-discrimination thresholds provide a useful complement to warble-tone and pure-tone audiometry.

Ampiroxicam, an anti-inflammatory agent which is a prodrug of piroxicam.

Ampiroxicam is a nonacidic ether carbonate prodrug of piroxicam. Our results demonstrate that, in contrast to piroxicam, ampiroxicam does not possess detectable prostaglandin synthesis inhibitory activity in vitro. Ampiroxicam, however, has similar in vivo potency to piroxicam in suppressing paw swelling in rat adjuvant arthritis. In an acute model of paw inflammation in rats, ampiroxicam is less potent than piroxicam itself: the ED50's of ampiroxicam are 9- and 3.5-fold higher than those of piroxicam following a single or multiple (5) daily oral doses, respectively. Using the phenylbenzoquinone stretching test as a method of evaluating acute analgetic activity, the ED50 for ampiroxicam is about 3-fold higher than that of piroxicam. These tests of activity share the property of being partially prostaglandin-dependent. Ampiroxicam itself is not observed in plasma after oral dosing to man, nor in the rat, dog, and monkey as reported here. Bioavailability studies show that conversion to piroxicam is about 100%, 90%, 70%, and 50% in these four species, respectively. These results indicate that ampiroxicam's anti-inflammatory activity is produced in vivo by conversion to piroxicam and support its credentials as an efficacious prodrug of piroxicam.

Effects of doxazosin on atherosclerosis in cholesterol-fed rabbits.

Doxazosin was administered to rabbits fed diets enriched in cholesterol and peanut oil for 7.5 or 12 weeks, in 2 separate experiments. Doxazosin suppressed the accumulation of cholesterol and formation of atherosclerotic plaques in the aortas of treated rabbits and prevented a diet-induced increase in aortic collagen and wall mass. Doxazosin was more effective in the thoracic and abdominal segments of the aorta than in the aortic arch. Pharmacokinetic analysis indicated that treated rabbits were exposed to concentrations of doxazosin, integrated over 24 h, which were consistent with the therapeutic range of doxazosin measured in patients treated for hypertension. Doxazosin did not alter serum levels of cholesterol or triglycerides, nor were there any consistent effects on glucose, free fatty acid or ketone levels. Hypotheses of the mechanism of action of doxazosin are discussed, including the possible involvement of alpha 1-adrenergic receptors in recruitment of smooth muscle cells by subintimal macrophages and nonadrenergic mechanisms of inhibition of lipid infiltration.

Characterization of the human lysyl oxidase gene locus.

Lysyl oxidase (EC 1.4.3.13) is a copper-dependent enzyme acting principally on collagen and elastin catalyzing the formation of aldehyde cross-links. It is also believed to possess a tumor suppressor activity as the anti-oncogene of ras. While rat, human, and mouse lysyl oxidase cDNAs have been cloned, little is known about the structure of the gene, its organization, or regulation. This paper describes the cloning of an intronic segment of the human lysyl oxidase gene. Sequence analysis defined the location of an intron that separates the prepro-coding segments from the segment encoding the catalytic domain. Genomic restriction mapping and gene copy number data established that multiple lysyl oxidase mRNA transcripts originate from a single gene and thus are products of alternative splicing. Northern analysis of adult and fetal fibroblast RNA showed a dominant approximately 4.3-kilobase lysyl oxidase mRNA transcript that varied in abundance as a function of cell line. These data are consistent with a complex mechanism regulating the expression of the lysyl oxidase gene.

Disposition of ampiroxicam, a prodrug of piroxicam, in man.

1. Ampiroxicam, a prodrug of the effective anti-inflammatory agent piroxicam, was completely converted to piroxicam after oral administration to man. 2. At clinical doses there was no detectable portal or systemic exposure of man to ampiroxicam, indicating that conversion to piroxicam was complete during the absorption process. 3. The pharmacokinetics of piroxicam from ampiroxicam were essentially the same as those after piroxicam itself except that Cmax was slightly lower and tmax was slightly longer after administration of ampiroxicam.

Parameters affecting hybridization of nucleic acids blotted onto nylon or nitrocellulose membranes.

Nine different nylon and nitrocellulose membranes were compared utilizing four different methods of attaching the nucleic acid target. Nylon membranes repeatedly demonstrated increased sensitivity as compared to nitrocellulose membranes. Sensitivity could also be enhanced by mildly denaturing the target prior to attachment onto the membrane. This was achieved by either UV cross-linking or baking.

The IHR-McCormick Automated Toy Discrimination test--description and initial evaluation.

McCormick's Toy Discrimination test allows a skilled audiologist to obtain word discrimination thresholds in quiet from children with mental ages of 2 years and above. A semi-automatic version of the test has been developed and evaluated by testing the hearing of 46 children and five adults. The equipment for the new version of the test both produces the stimuli and scores the responses, thereby reducing the burden on the tester. It is reliable and allows greater sensitivity than the manual test as well as solving problems of standardization and calibration.

Liquid chromatographic analysis of doxazosin in human serum with manual and robotic sample preparation.

A specific method for the determination of the antihypertensive drug doxazosin in human serum is described. The method utilizes the related drug prazosin as an internal standard and is based on a simple extraction scheme followed by analysis by reversed-phase ion suppression high-performance liquid chromatography (HPLC) on an alumina-based column with fluorescence detection. The method is completely automated with a flexible robotic system for the analysis of drugs in biological fluids. The robotic automation of the method allows a 20% increase in the sample throughput and the savings of about 7 man-hours a day. Both the manual and robotic procedures yield precise quantitative results over the therapeutically relevant concentration range of 0.5 to 20 ng/mL of serum.

O.R. custom packs: no easy answers.

The use of custom sterile packs continues to grow in popularity as hospitals look for different ways to reduce the cost of providing health care services. Mounting evidence appears to indicate, however, that the real beneficiaries of custom packs and the vendors themselves.