The Longitudinal Examination of Arthritis Pain (LEAP) study: relationships between weekly fluctuations in patient-rated joint pain and other health outcomes

OBJECTIVE: To examine relationships between weekly fluctuations in self-rated joint pain and other health outcomes among adults with osteoarthritis (OA). METHODS: In this observational study, 287 adults (aged > or = 50 yrs) with hip or knee OA were recruited from 16 medical practices across the United States. Patients were telephoned weekly for 12 weeks to assess pain/stiffness, daily activities/function, productivity, emotional well-being, quality of life, and healthcare utilization. Associations between changes in joint pain levels and other health outcomes were evaluated using a generalized estimating equation model. RESULTS: The mean (SD) pain score at Week 1 was 4.2 (2.1) on the Western Ontario and McMaster Universities OA index (WOMAC) pain subscale (0 = no pain, 10 = extreme pain); during the study, 49% of patients reported a between-week fluctuation of > or = 2 points. A 2-point decrease in WOMAC pain subscale score was associated with a 22% decrease in number of days of limited activity/week (beta = -0.107; 95% confidence interval -0.163, -0.051); a 48% decrease in number of days of missed work/week (beta = -0.217; 95% CI -0.395, -0.039); a 14% decrease in number of nights with pain-related sleep interference/week (beta = -0.068; 95% CI -0.109, -0.027). Patients were 1.6 times more likely to contact a healthcare provider when their pain changed from "acceptable" to "unacceptable." CONCLUSION:Weekly fluctuations in pain levels and other health outcomes were identified among adults with OA. Decreases in patient-reported pain were associated with improvements in daily activities/functioning and decreases in work absenteeism, sleep interference, and healthcare resource use.     

Loss of neurturin in frog--comparative genomics study of GDNF family ligand-receptor pairs

Four different GDNF family ligand (GFL)-receptor (GFRalpha) binding pairs exist in mammals, and they all signal via the RET receptor tyrosine kinase. However, the evolution of these molecules is poorly understood. We identified orthologs of all four GFRalpha receptors and GRAL (GDNF Receptor Alpha-Like) in all vertebrate classes, and a predicted GFR-like protein in several invertebrates. In addition, Gas1 (growth arrest-specific 1), a distant member of the GFR-superfamily, is present in both vertebrates and invertebrates. Analysis of exon structures suggests a common origin of GFR-superfamily proteins and early divergence of Gas1 from the common ancestor. Bony fishes have orthologs of all four mammalian GFLs, consistent with genome duplications in early vertebrates. Surprisingly, the clawed frog and chicken have only three GFLs: synteny analysis indicates loss of neurturin in frog and of persephin in chicken. Evolutionary trace analysis and protein structure homology modeling points at GDNF as the endogenous ligand of frog GFRalpha2.     

Correction of chronic lunotriquetral instability using extensor retinacular split: a retrospective study of 26 patients

Arthroscopy offers a welcome and reliable supplement to the current tool set for the diagnosis of lunotriquetral (LT) instability. This study reports the findings of LT-lesions during arthroscopy and the clinical results obtained after using dorsal stabilisation in its surgical management using extensor retinacular split. LT-instability of grade I-III was diagnosed in 26 patients. Imaging results were normal, Reagan's ballottement and Watson tests were positive in 47% and 79%, respectively. After arthroscopic diagnosis, the procedure was immediately continued with an open repair utilising an 8-10 mm wide and radial-based extensor retinacular split for dorsal capsular reinforcement. At 39 months (range: 14 to 84) follow-up, 64% had no or only occasional mild pain and 36% had pain with overuse or lifting. Overall scoring encompassing pain, patient satisfaction, range of motion and grip strength, was excellent in 24% and good in 64%. Only three patients had fair results, one after a further injury leading to distal radio-ulnar joint (DRUJ) instability, and two with concurrent DRUJ-stabilisation. One further patient required a secondary procedure. Arthroscopy seems to allow accurate diagnosis of LT-instability and can be continued in the same session using a straightforward reconstruction procedure providing satisfactory results.     

Is it painful or not? Discriminant validity of the Behavioral Indicators of Infant Pain (BIIP) scale

OBJECTIVES: To evaluate the ability of the Behavioral Indicators of Infant Pain (BIIP) scale to discriminate between skin-breaking and nonskin breaking procedures, and to identify sensitized pain responses in preterm infants in the neonatal intensive care unit (NICU). METHODS: Sixty-nine infants born between 24 and 32 weeks gestational age were assessed at 32 weeks postconceptional age during blood collection on one day (procedure A), and then on another day during blood collection preceded by a diaper change (procedure B). Procedure order was randomized. Outcome measures were changes in BIIP coded from continuous bedside video recordings and changes in heart rate (HR). RESULTS: During blood collection (procedure A), BIIP scores (P<0.0001) and mean HR (P<0.0001) were higher than during the diaper change and higher when the infants had had a preceding diaper change (procedure B vs. procedure A) (P<0.03). HR changed from baseline to the stressors for each procedure. No differences in mean HR were observed during Lance phase between the procedure A and the B blood collection; however, HR remained elevated significantly during the Recovery phase when blood collection was preceded by the diaper change (P<0.03). DISCUSSION: The BIIP scale is reliable, accurate, and valid assessment for measuring acute pain in preterm infants in the NICU. This assessment combines the relatively most specific, anatomically based, theoretically derived indicators; and it allows evaluation of behavioral and physiologic pain responses separately.     

<Emphasis Type="Italic">CYP1A1</Emphasis> and <Emphasis Type="Italic">CYP1B1</Emphasis> genetic polymorphisms,smoking and breast cancer risk in a Finnish Caucasian population

We investigated the associations between two CYP1A1 polymorphisms (Ile462Val and Thr461Asn) and one CYP1B1 polymorphism (Leu432Val) and breast cancer risk. The study population consisted of 483 breast cancer patients and 482 healthy population controls, all of homogenous Finnish origin. No statistically significant overall associations were found between the CYP1A1 and CYP1B1 genotypes and breast cancer risk. However, a significant increase in the breast cancer risk was seen for women who had smoked 1–9 cigarettes/day and carried the CYP1B1 432Val allele; the OR was 2.6 (95% CI 1.07–6.46) for women carrying the Leu/Val genotype and 5.1 (95% CI 1.30–19.89, P for trend 0.005) for women with the Val/Val genotype compared to similarly smoking women homozygous for the 432Leu allele. Furthermore, when CYP1B1 genotypes were combined with the previously analyzed N-acetyl transferase (NAT2) genotypes, a significant increase in breast cancer risk was found among women who had at least one CYP1B1 432Val allele together with the NAT2 slow acetylator genotype (OR 1.52; 95% CI 1.03–2.24) compared to women carrying a combination of CYP1B1 Leu/Leu and NAT2 rapid acetylator genotypes. This risk was seen to be confined to ever smokers; the OR was 2.46 (95% CI 1.11–5.45) for ever smokers carrying at least one CYP1B1 432Val allele together with the NAT2 slow acetylator genotype compared to ever smokers with the CYP1B1 Leu/Leu and NAT2 rapid acetylator genotype combination. Our results suggest that the CYP1B1 polymorphism may be an important modifier of breast cancer risk in Finnish Caucasian women who have been exposed to tobacco smoke and/or carry the NAT2 slow acetylator genotype.