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A new self-gelating triterpenoid natural product has been isolated from the bark of the silver fir, Abies alba. The structure is desmethylabietospiran (3) on the basis of chemical and spectroscopic evidence. Also reported is a more efficient isolation procedure of abietospiran (1) from A. alba.

Objective: To assess the repeatability and validity of the electromagnetic 3-dimensional tracking system, Fastrak, in measuring cervical spine and shoulder movement in patients with ankylosing spondylitis (AS)., Methods: Fifty patients with AS had their cervical spine and shoulder movements measured on up to 3 occasions with the Fastrak. Patients also completed disease-specific and generic patient assessed health instruments, and their spinal mobility was assessed by tape measure methods. Repeatability over 2 weeks was assessed using intraclass correlation coefficients (ICC). Fastrak measurements were compared between patients with different self-ratings of AS related health. Comparisons between the Fastrak measurements and patient assessed health instruments and tape measurements were made using Spearman correlations and multilevel modeling., Results: Patients with AS tended to be limited in both cervical spine and shoulder movements. ICC were all > 0.80 (except shoulder extension, 0.75), indicating substantial reliability. Fastrak was able to differentiate between patients with a high self-rating of AS related health and those with a poorer rating. Cervical spine flexion and shoulder flexion and abduction were most strongly related to the patient assessed health instruments, although the shoulder movements had limited relationships with the tape measurements of spinal mobility., Conclusion: The Fastrak appears to be reliable and valid in an AS population. Shoulder movements tended to have a stronger relationship with the patient assessed health instruments than cervical spine movements. Shoulder movement may be more related to everyday function measured by these instruments, which indicates the importance of this joint in assessment of AS.

Deregulated tumour expression of p16INK4a has previously been described in association with clinical progression in sporadic colorectal cancer patients (CRC). Furthermore, p16INK4a promoter hypermethylation leading to gene silencing has been shown to occur in advanced colorectal tumours and has been associated with patient survival. p16INK4a is polymorphic, with variant alleles being associated with tumour progression in melanoma. In this study we have examined p16INK4a polymorphism as a marker of tumour progression in sporadic CRC. Polymorphic sites G/A(442), C/G(500), and C/T(540), were studied, these alleles obeyed Hardy Weinberg equilibrium in a control group, but not in the CRC cases. G/A(442) and CG(500) alleles were in linkage disequilibrium in both cases and controls. In controls the C/T(540) alleles demonstrated no linkage with either other site, whilst an association was demonstrated between C/G(500) and C/T(540) alleles in the cases (p=0.011). Furthermore, the distribution of C/T(540) genotypes was different between the groups (p=0.002). Within the CRC cases, patients with the GG(442) genotype were more commonly associated with decreased tumour differentiation (p=0.018), advancing Dukes' stage (p=0.006) and T-stage (p=0.007) than patients with the GA(442) and AA(442) genotypes. Patients with the CC(500) genotype were more commonly associated with decreased tumour differentiation (p=0.012), advancing Dukes' stage (p=0.015), and N-stage (p=0.031). No associations between patient C/T(540) genotype and clinical prognostic parameters were found. An analysis of patient tumour expression with p16INK4a genotype revealed patients with the CC(500) genotype were more commonly associated with reduced tumour p16 expression (p=0.046). In summary our data indicate that p16INK4a polymorphism is associated with tumour progression in patients with sporadic CRC.

After first presentation with a basal cell carcinoma (BCC), patients demonstrate interindividual diversity in the rate of development of further BCCs (number/year of follow-up). The mechanism for this variation is unknown. In this study, we evaluated whether PTCH variants mediate this phenomenon. We used negative binomial regression analysis to identify associations between BCC numbers/year and host characteristics, parameters of exposure to ultraviolet radiation (UVR), and PTCH exon 12(1686) C/T, intron 15(2560+9) G/C, and exon 23(3944) C/T genotypes and haplotypes in 279 BCC cases who presented with an initial tumor on the head/neck. PTCH genotypes were not significantly associated with BCCs/year, although cases with two copies of the C1686-C3944 haplotype developed significantly fewer BCCs/year than those without this haplotype (rate ratio = 0.44; 95% CI = 0.27-0.71). Cases with one copy of T1686-T3944 developed more BCCs/year (rate ratio = 2.46; 95% CI = 1.27-3.97) than those without the haplotype. We found no significant associations between BCCs/year and the other PTCH haplotypes studied. We reexamined the association of C1686-C3944 with BCCs/year in a model that included UVR exposure parameters (sunburning in childhood, sunbathing score, intermittency of exposure between 40 and 60 years of age, exposure in hours/year) and skin type, gender, and age at first presentation. The association between C1686-C3944 and BCCs/year remained significant (rate ratio = 0.44; 95% CI = 0.26-0.73 for two copies of the haplotype). The data show that allelic variation in PTCH contributes to the rate of development of BCC.

Ultraviolet radiation (UVR) exposure may protect against prostate cancer development via a mechanism involving vitamin D. The vitamin D receptor (VDR) gene is therefore a candidate susceptibility factor for prostate cancer. This possibility has been previously investigated with conflicting results. We examined the association of VDR genotypes (variants at the CDX-2, Fok1, and Taq1 sites), haplotypes, and genotype combinations with risk by studying 368 prostate cancer and 243 benign prostatic hypertrophy (BPH) patients. CDX-2, Fok1, and Taq1 genotype and haplotype frequencies were not significantly different in cancer and BPH patients. As the impact of VDR polymorphisms may depend on UVR exposure, we studied associations of variants with risk in men stratified into low (below median) and high (above median) cumulative exposure/year groups. In men with UVR exposure above the median (1,100 hr/year), CDX-2 GA and AA (odds ratios [OR] = 2.11 and 2.02, respectively) and Fok1 ff (OR = 2.91) were associated with increased prostate cancer risk. No associations were observed for Taq1 genotypes. Of the genotype combinations, relative to all other CDX-2 and Taq1 and combinations, GGTT (P = 0.022, OR = 0.30), and relative to all other Fok1 and Taq1 combinations, FFTT (P = 0.026, OR = 0.35) were associated with reduced prostate cancer risk in the presence of the main effects. None of the other two- or three-genotype combinations was associated with risk. These data indicate that VDR variants influence prostate cancer risk and that this association is dependent on the extent of UVR exposure., (Copyright 2004 Wiley-Liss, Inc.)

A linear mixed model is used to detect a change, if any, in the prescribing habits in the UK at the general practice (family medicine) level due to an educational intervention given repeated measures data before and after the intervention and a control group. Inferences are corrected for general practice size and fundholding status. The estimates of the model parameters are obtained using Bayesian inference by applying Gibbs sampling. We develop three different priors for the parameters of the model. These three priors correspond to 'sceptical,' 'reference' and 'enthusiastic' priors in terms of the opinion about the treatment effects that they represent. We compare the results obtained by using these three priors for the parameters in the random effects model.

Maternal factors including atopy and smoking during pregnancy are associated with asthma risk during childhood. Suggested mechanisms include transmission of specific maternal alleles and maternal influences on the intrauterine environment. We have previously shown that polymorphism in glutathione S-transferase, GSTP1 is associated with airway hyperresponsiveness (AHR) and atopy in adults. We now hypothesise that GSTP1 genotypes in the mother and child, but not the father, mediate asthma phenotypes in the child. One hundred and forty-five Caucasian families were recruited via an asthmatic proband aged 7-18 years. Atopy and asthma were assessed using a questionnaire, skin prick testing, serum IgE, spirometry and methacholine challenge (PC20, dose-response slope--DRS). GSTP1 genotyping was determined using PCR. GSTP1 Val105/Val105 genotype in the child was associated with a reduced risk of atopy (P = 0.038) and AHR (PC20, P = 0.046; DRS, P = 0.032). In mothers (P = 0.014) but not fathers (P = 0.623), Val105/Val105 was associated with a reduced risk of AHR in the child. We have identified, for the first time, an association between maternal genotype and the child's asthma phenotype that appears not to be due to transmission of specific maternal alleles. This preliminary data supports the view of in utero effects of maternal genotype and adds new insights into the possible mechanisms by which maternal factors may influence development of childhood asthma.

Background and Purpose: Patients who have had a stroke are at risk of hypoxia through alterations in the central regulation of respiration, through aspiration, and through respiratory muscle weakness. Sleep-related breathing disorders are common and may lead to episodes of nocturnal hypoxia even when daytime oxygenation is normal. The aim of this study was to assess the prevalence of unexpected nocturnal hypoxia in stroke patients., Methods: Consecutive adult patients with stroke were recruited within 72 hours of admission to hospital. Patients with indications for oxygen treatment were excluded. Older adults from the local community were recruited as control subjects. Oxygenation was assessed by pulse oximetry (Minolta 3i) for 5 minutes when awake before bedtime and continuously from 11 pm until 7 am., Results: Of the 238 potentially eligible stroke patients, 120 were excluded because they required oxygen, 118 were recruited, and 100 had adequate pulse oximetry data. The mean+/-SD age was 74+/-8 years for stroke patients and 72+/-8 years for control subjects (n=85). Mean awake oxygen saturation (So2) was 94.5+/-1.7% for the stroke group and 95.8+/-1.7% for the control group (P<0.001). Mean nocturnal So2 was 93.5+/-1.9% in stroke patients and 94.3+/-1.9% in control subjects (P<0.01). Stroke patients had a higher oxygen desaturation index (ODI 4%) (8.9 versus 2.1, P<0.001). In addition, 23% of stroke patients spent >30 minutes with So2 <90% during the night., Conclusions: Oxygen saturation at night is approximately 1% lower than when awake. Almost a quarter of stroke patients who are normoxic at screening during the day spend >30 minutes with an oxygen saturation <90%.

A method is proposed for comparing two normal means when the data consist of some observations that are correlated and others that are uncorrelated. Typically, such data will consist of one subsample in which the observations for treatment 1 and treatment 2 are independent of each other, and another subsample which consists of paired observations taken under both treatments. The proposed method is developed using asymptotic results and is evaluated using simulation. The simulation results indicate that the proposed method can provide substantial improvement in type I error rate and power when compared with standard methods of analysis., (Copyright 2003 John Wiley & Sons, Ltd.)

Basal cell carcinoma (BCC) patients demonstrate marked variation in tumour numbers and site. Previous studies also show an association between age at first BCC presentation and development of BCC on the trunk. In this study we have investigated the association between age at first presentation and the rate of development of truncal and non-truncal tumours in 747 patients with BCC. We used negative binomial regression analysis to show that increasing age at first presentation was associated with an increased rate of BCC development (rate ratio 1.01/year, 95% CI 1.01-1.02, P < 0.001). In particular, development of tumours was greater in cases aged 60.0-69.9, 70.0-79.9 and 80.0-89.9 years than in those 40.0-49.9 years (P = 0.05, 0.01 and 0.039, respectively). While few cases aged over 70 years of age first present with a truncal BCC, the numbers of BCC/year were greater than in those with a head/neck BCC. The data suggest different genetic factors mediate the appearance of BCC in patients of different ages particularly those aged above and below 60 years.

Linear mixed models are used to detect a change, if any, in prescribing habits at the primary care practice level due to an educational intervention given repeated measures data before and after intervention and a control group. Inferences are corrected for general practice size, fundholding status and baseline prescribing. The correlation structure is discussed and the results for multilevel modelling using MLwiN and NLME version 3.0 are compared., (Copyright 2002 John Wiley & Sons, Ltd.)