Genes associated with telomerase activity levels in esophageal carcinoma cell lines.

Telomerase activity levels have been shown to correlate with tumor progression in several malignancies. However, the genetic regulation of telomerase activity levels is not fully understood. The aim of the present study has been to identify a gene expression profile, predicting correlation with the telomerase-activity test. Ten human esophageal carcinoma cell lines were investigated using the telomerase activity assay (TRAPeze) Telomerase Detection Kit), followed by further characterization using the GeneChip Human Genome U133A 2.0 Array (Affymetrics Inc., USA), including 14 500 human genes. Telomerase activity levels were detected in all cell lines with a broad range of activity levels. Using a high correlation coefficient, r > 0.90, the following genes were found to be positively correlated with telomerase activity levels: N-myristoyltransferase 2; ribosomal protein L3; retinoblastoma-like 2 (pRb2/p130); and cyclin G2. Only one gene was negatively correlated with telomerase activity levels, zinc finger protein 207. In conclusion, the present microarray data provide primary validation data indicating possible candidates for prognostic and prediction factors in esophageal cancer in relation to telomerase activity.

Diverse pattern of protease inhibitor resistance mutations in HIV-1 infected patients failing nelfinavir.

The aim of the study was to describe the pattern of resistance mutations in human immunodeficiency virus type 1 (HIV-1) infected patients experiencing their first protease inhibitor (PI) failure on nelfinavir (NFV)-containing therapy. Earlier PI-naïve patients (n=172) with NFV-containing therapy were therefore retrospectively studied. Plasma HIV RNA from 43 failing patients was sequenced. In addition, virus from the baseline was sequenced in 29 patients. Failure was defined as two consecutive measurements of viral load of >50 copies/ml after 6 months treatment. Subtyping was done in most patients (n=118). At baseline, the V82A mutation was found in four PI-naïve patients of whom two failed therapy exhibiting this mutation. At therapy failure, 17 of the 43 (40%) patients had primary PI mutations. In nine subjects, RTI-mutations only were found and 17 patients had a wild-type virus. Patients with primary PI and/or RTI mutations had a higher viral load at failure than those who failed with wild-type virus. A surprisingly diverse pattern of primary PI mutations was seen: M46I (n=7), D30N (n=6), L90M (n=5), and V82A (n=4). Four patients exhibited more than one primary PI mutation. PI-naïve patients in Sweden may harbor PI-resistant virus and resistance testing should be considered before treatment. Patients who fail NFV may develop the M46I mutation, which has been related earlier to mainly other PI. The diverse pattern of the evolved PI-mutations and the relative low occurrence of the D30N mutation in the material was unexpected and did not seem to be related to the viral subtype.

Recent origin of human immunodeficiency virus type 1 variants in resting CD4+ T lymphocytes in untreated and suboptimally treated subjects.

Resting CD4(+) T lymphocytes are an important reservoir for human immunodeficiency virus type 1 (HIV-1) in treated patients with undetectable viremia. The knowledge of viral persistence in these cells is limited, however, for patients without treatment or patients for whom treatment is failing; therefore, this reservoir in such patients was characterized. Virus variants were characterized in 3 subjects who were followed-up from primary HIV-1 infection and 5 treatment-experienced subjects. No founder viral sequences and only a minority of the earlier identified drug-induced mutations were found in the resting T lymphocytes. Instead, the viral sequences were closely related to those detected simultaneously in plasma, except in 2 treatment-experienced subjects. Thus, a turnover and replenishment of this virus reservoir in peripheral blood is likely to occur in most persons with detectable viremia. However, infrequently the virus variants in plasma and resting T cells seem to be derived from independent sources.

Sound quality and speech reception for prescribed hearing aid frequency responses.

Four different prescriptions of hearing aid insertion gain versus frequency were validated with a group of 26 moderately hearing-impaired, elderly hearing aid users. Three prescriptions were based on calculating the loudness and articulation index (AI) for aided speech, and ranged from a frequency response with moderate high-frequency emphasis, restoring normal loudness for speech peaks, to a response with the greatest high-frequency emphasis, maximizing the AI. The fourth prescription was a well-established formula of the half-gain type. The frequency responses were evaluated by paired comparison ratings of the pleasantness and intelligibility of speech in noise, and by speech identification tests in noise. The subjects rated the flattest response as significantly more pleasant than the other responses, and significantly more intelligible than the prescription with maximal high-frequency emphasis. There were no detectable differences in signal/noise ratios required for 50% speech identification. These results indicate that a prescription that restores normal loudness for speech peaks in each critical band is probably more easily accepted than either a procedure which is intended to make all speech bands equally loud, or a prescription which maximizes the AI.

Preferred hearing aid gain in everyday use after prescriptive fitting.

The insertion gain preferred by a group of 26 moderately hearing-impaired, elderly hearing-aid users was investigated in everyday listening situations. The subjects used monaural behind-the-ear aids, carefully fitted according to a prescription formula of the half-gain type, validated and used at National Acoustic Laboratories, Australia. The fitting was checked with real-ear measurements of insertion gain and reviewed at one or more follow-up sessions. The subjects were strictly instructed to try the recommended volume control setting before reporting which setting they preferred. The prescription significantly over-estimated preferred gain by about 7 dB. No correlation could be detected between prescribed versus preferred gain differences and the amount of previous hearing-aid use or the degree of subjective hearing problems.

Clinical trials with a programmable hearing aid set for various listening environments.

A conventional hearing aid has a frequency response that does not change much at normal listening levels. It is therefore unlikely that optimal speech intelligibility and optimal listening comfort can be obtained simultaneously, or in different listening environments. With a programmable hearing aid with multiple memories the listener can choose between a range of sound pictures, which increases the chance of finding a suitable frequency curve for each listening situation. The programmable hearing aid with eight separate settings stored in eight memories, was compared with personal hearing aids fitted according to the recommendations of the National Acoustic Laboratories (NAL) by 22 experienced hearing aid users. One memory of the programmable hearing aid was initially fitted according to the NAL recommendation. The other memories were programmed to give variations around that recommendation. One aim was to investigate whether the hearing-impaired user took advantage of different frequency responses to achieve listening improvements in acoustically different environments. Another aim was to evaluate the ergonomic and acoustical features of the programmable hearing aid, compared with other well fitted hearing aids. The evaluations were based on comparisons of the test hearing aid to the personal aid for each subject, looking at speech tests, direct paired comparison judgements, sound quality judgements and interviews. A majority of the subjects experienced substantial benefit from being able to use different frequency response curves in different environments. With the test hearing aid the subjects performed better in speech discrimination tests in noise.(ABSTRACT TRUNCATED AT 250 WORDS)

The double mask--a new local scavenging system for anaesthetic gases and volatile agents.

The double mask, a new concept for local scavenging of anaesthetic gases escaping around face masks and from endotracheal tubes, is described. The system consists of a flexible silicone mask into which the anaesthetic gas mixture is led through a flow distributor which is necessary for adequate scavenging. A rigid transparent polysulphone shell surrounds the inner mask, and escaping gas is evacuated via the 3-4 mm slot between the two masks by a fan, centrally located outside the operating-room. With this system, the anaesthetist's exposure to nitrous oxide during mask anaesthesia was reduced from 145 +/- 29 to 15 +/- 3 ppm (mean +/- s.e. mean, P less than 0.001) and to halothane from 2.9 +/- 1.1 to 0.5 +/- 0.1 ppm (mean +/- s.e. mean, P less than 0.05), as measured in 32 patients aged 1-74 years. The double-mask system provided safe and adequate mask anaesthesia, as judged from inspired concentrations of anaesthetic and fresh gases and transcutaneous and blood gases in 24 patients. The noise level was low with a mean value under regular operating-room conditions around 45 dB(A) in the low frequency range. It is concluded that using the scavenging conditions provided by the system, the Swedish limits for anaesthesiologists' gas exposure could be reduced to the levels recommended by the US National Institute of Occupational Safety and Health (25 ppm for nitrous oxide and 0.5 ppm for halothane).