A new HLA-B allele, B*1565, identified in three unrelated samples

Anew human leukocyte antigen-B allele, B*1565, has been identified during routine typing of cord blood samples. Subsequently, two individuals from the same family as the first cord blood sample plus two unrelated Australian Bone Marrow Donor Registry samples have been found to carry this novel allele.     

Comparison between prospective and retrospective evaluation of Crohn's disease activity index

The Crohn's disease activity index (CDAI) is the most widely used measure of clinical disease activity in patients entered into clinical trials. The prospective nature of the CDAI calculation precludes its use as a clinical assessment tool. We compared the retrospective evaluation of the CDAI with the prospective evaluation in a heterogeneous patient population of 100 patients with Crohn's disease. The correlation between the two assessment methods was good with an r-value of 0.84 (p < 0,0001). There was a tendency of patients with a high retrospective CDAI to have a lower prospective CDAI which is explained by intention to treat. This study shows that a retrospective assisted evaluation of the CDAI is as accurate as the traditional prospective evaluation.     

Discovery and development of biomarkers of neurological disease

The identification of clinically relevant biomarkers for neurological diseases poses unique challenges. These include an historical lack of availability of relevant tissues from the site of pathology, relatively poorly matured techniques for disease diagnosis, the complexity and cellular heterogeneity of the brain, and a clear deficiency of models for functional validation of candidate biomarkers. Here, the unique challenges that neurological disorders introduce to biomarker discovery are described and how modern technological advances in genomics, proteomics and metabolomics are overcoming these obstacles and are driving the discovery of novel biomarkers to improve early diagnosis and therapeutic treatment is discussed.     

Gender effects on high frequency distortion product otoacoustic emissions in humans

OBJECTIVE: Gender has been reported to affect many tests of the auditory system, including distortion product otoacoustic emission (DPOAE) group delay and level when elicited with lower frequency stimuli (<8 kHz). Using custom equipment, the effect of gender on DPOAEs at higher frequencies was explored. It is expected that differences in group delay reported at very low frequencies (e.g., 0.78 Hz) will not be replicated at higher frequencies. Additionally, it was hypothesized that female subjects would display larger-level DPOAEs at higher frequencies, based on evidence that female subjects tend to have larger emissions when elicited with lower frequency stimuli. DESIGN: DPOAEs were measured in 37 subjects (20 females and 17 males) with normal behavioral thresholds, middle ear function, and present acoustic reflexes at 1 kHz with contralateral stimulation. Behavioral thresholds were measured through 16 kHz using Békèsy tracking. Ratio and frequency sweeps were used to calculate DPOAE group delay and measure DPOAE levels, respectively. Ratio sweeps were obtained at f2 frequencies of 1, 2, 4, 8, 10, 12, 14, and 16 kHz, with L1 = 60 and L2 = 45 dB SPL, with the ratio (f2/f1) varied from 1.11 to 1.3. Frequency sweeps were measured with L1 = 60 and L2 = 45 dB SPL and an f2/f1 of 1.2 at discrete f2 frequencies between 1 and 16 kHz. Data were subjected to repeated-measures analysis of variance. RESULTS: Significant frequency-by-gender interactions were found for group delay (for data from 1 to 8 kHz) and level (for data from 9 to 15 kHz). The frequency-by-gender interaction and the main effect of gender were not significant for the behavioral results. CONCLUSIONS: Gender-based norms for auditory-evoked potentials measures are standard in clinical settings. The results of the present study, in agreement with previous studies, indicate that significant interactions exist between gender and DPOAE group delay values in the lower frequencies, and between gender and DPOAE levels at the higher frequencies. To reach the goal of using high frequency DPOAEs in clinical protocols, such as for auditory neuropathy/dys-synchrony diagnosis and ototoxicity monitoring, DPOAEs elicited with conventional and higher frequency stimuli must be understood, including the role of gender to determine if an effect on clinical protocols would exist.     

Regression of melanoma, but not keratoacanthoma, is associated with increased HLA-B22 and decreased HLA-B27 and HLA-DR1

Sixty three Caucasian patients with either melanoma, keratoacanthoma or squamous cell carcinoma were human leucocyte antigen (HLA) typed. The regressing tumour groups were compared with their non-regressing counterparts, and the patient groups were compared with a control Caucasian population. Melanoma patients showing histological regression were more likely to be HLA-B22 positive, and HLA-B27 and -DR1 negative, than those without features of regression. When compared with a control population, the group of melanoma patients were more likely to be HLA-B22 positive. Comparison of the group of keratoacanthomas, a self-regressing tumour, and the group of squamous cell carcinomas, a non-regressing tumour, did not show any significant differences in HLA typing.     

Immune response genes in the post-Q-fever fatigue syndrome, Q fever endocarditis and uncomplicated acute primary Q fever

BACKGROUND: The influence of immune response gene variations on the development of chronic complications of Q fever is presently unclear. AIM: To compare the frequencies of allelic polymorphisms in immune response genes in different Q fever patient groups. DESIGN: Genetic association study. METHODS: We measured the frequencies of immune response gene variants in: (i) an expanded group of 31 post-Q-fever fatigue patients (QFS); (ii) 22 Q fever endocarditis patients (QFE); and (iii) 22 patients who made an uncomplicated recovery from their initial attack of primary acute Q fever, comparing them with various standard control panels from the general population. RESULTS: There were significant differences between the three Q fever groups. QFS patients differed from both QFE and uncomplicated patients and controls in the frequency of carriage of HLA-DRB1*11 and of the 2/2 genotype of the interferon-gamma intron1 microsatellite. Carriage of the HLA DRB1*11 allele was associated with reduced interferon-gamma and IL-2 responses from PBMC stimulated with ligand in short-term culture. QFE showed differences in the IL-10 promoter microsatellites R and G and had higher frequencies of the TNF-alpha receptor II 196R polymorphism. Q fever patients who had made an uncomplicated recovery differed from those with QFS or QFE, but were not significantly different in allelic frequencies to the control panels. DISCUSSION: These immunogenetic differences support the concept of different immune states in chronic Q fever, determined by genetic variations in host immune responses, rather than by solely properties of Coxiella burnetii.     

Professionals' views and experiences of using outcome measures in palliative care

In palliative care, outcome measures are increasingly used to aid clinical practice, conduct audit and research. The objective of this study was to elicit professionals' views and experiences of using outcome measures, paying special attention to the Palliative care Outcome Scale (POS). This article presents the results of a qualitative study of 26 professionals, experienced in using the POS, who were invited to participate in semi-structured telephone interviews. Of those invited, 22 people took part. Participants' comments were noted verbatim through the interviews and data subjected to content analysis. Analysis of data identified a number of key themes surrounding outcome measures, notably their reasons for use, application in clinical settings and a range of professionals' attitudes. The article concludes that understanding the process of outcome measures is important for improving their implementation. When undertaking further research, attention should be paid to the wider social, cultural and structural contexts, as factors that can influence the implementation of outcome measures. As the drive towards outcome measures continues, it is essential that measures are not developed in a vacuum. Instead they should always be informed by the needs and experiences of individuals and services.