Citations

The purpose of this study was to describe a modification of the Massachusetts General Hospital (MMGH) tendon repair and to compare it with three other suture techniques. Twenty human flexor digitorum profundus (FDP) tendons were randomly assigned to the modified Pennington (MP) suture and the MMGH suture. These were compared to the modified Kessler (MK) and Massachusetts General Hospital (MGH) sutures, using data from a previous study. All tendons were repaired with a similar epitendinous stitch and core sutures of 4-0 FiberWire. There was no significant difference in the normalized gliding resistance within the two-strand or four-strand core repair groups. The MP suture had significantly higher 2 mm gap force and ultimate load to failure than the MK suture. The MMGH suture had significantly higher 2 mm gap force and maximum failure ultimate load than the MGH suture. All repairs failed by knot unravelling.

Abstract Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08–1.14, P = 7 × 10−18) for invasive breast cancer and 1.10 (95% CI = 1.01–1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99–1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12–1.20, P = 1 × 10−18 vs. OR = 1.03, 95% CI = 0.99–1.07, P = 0.2 for PR-negative disease; Pheterogeneity = 2 × 10−7); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14–1.25), 1.13 (1.09–1.16), and 1.04 (0.99–1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10−7]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222–31. ©2011 AACR.

Direct sampling of the human spermatic veins has disclosed concomitant LH and testosterone (T) pulses, suggesting pulsatile LH concentration-dependent stimulation of T secretion. However, studies to date have examined this hypothesis using only pharmacological stimulation with hCG. The present study tests the hypothesis that age is marked by decreased T secretory responses to repeated near-physiological iv pulses of recombinant human LH administered in a Clinical Translational Science Center. Participants included 92 healthy men aged 18–75 yr with BMI 18–34 kg/m2. The contribution of endogenous LH pulses was minimized by combined injection of a selective GnRH receptor antagonist sc and successive pulses of biosynthetic LH iv. A new analytical dose response model was applied to estimate the properties of exogenous LH's drive of T secretion. Regression of LH-T dose response potency estimates on age showed that the efficacy of pulses of biosynthetic LH progressively decreased with age ( P = 0.014, r = 0.26). Testis sensitivity to exogenous LH pulses also declined with age ( P = 0.011, r = 0.27). Moreover, estimated Leydig cell downregulation by LH pulses rose significantly with age ( P = 0.039, r = 0.22). These outcomes were selective, since the recovery potency of infused LH was not affected by age but was reduced by increasing BMI ( P = 0.011, r = 0.27). Assuming stable bioactivity of infused recombinant human LH, these novel data indicate that factors associated with age and BMI attenuate LH efficacy and testis sensitivity and augment Leydig cell downregulation in healthy men.

Background The etiology of carpal tunnel syndrome (CTS) remains idiopathic in many cases. Noninflammatory fibrosis of the subsynovial connective tissue (SSCT) within the carpal tunnel is common in CTS, and some clinicians have hypothesized that this fibrosis might be a cause rather than an effect of CTS. An animal model in which to test this hypothesis would be useful. The principal objective of this study was to investigate the effect of a surgical injury on SSCT fibrosis and median nerve function within the carpal tunnel in an in vivo rabbit model. Methods Rabbits were sacrificed 12 weeks after surgery and were evaluated by mechanical testing, histology, transmission and scanning electron microscopy, and electrophysiology. Results SSCT fibroblast density ( p<0.0001) and collagen fiber size ( p=0.0004) were significantly higher, and the median nerve distal motor amplitude was significantly lower ( p=0.0018), in the tendon injury group SSCT than in either the sham or control groups. Conclusions Our findings are similar to those seen in patients with carpal tunnel syndrome and suggest that the tendon injury procedure may be the basis of a new animal model of SSCT injury and, possibly, CTS.

Abstract Increased alcohol consumption is a putative colorectal cancer (CRC) risk factor. However, existing data are less conclusive for women than men. Also, to date, relatively few studies have reported alcohol-related CRC risks based on molecularly defined tumor subtypes. We evaluated associations between alcohol intake and incident CRC, overall and by microsatellite instability [MSI high (MSI-H) or MSI low/microsatellite stable (MSI-L/MSS)], CpG island methylator phenotype (CIMP positive or CIMP negative), and BRAF mutation (mutated or wild-type) status in the prospective, population-based Iowa Women's Health Study (IWHS; n = 41,836). Subjects were 55 to 69 years at baseline (1986), and exposure data were obtained by self-report. Incident CRCs were prospectively identified and archived, paraffin-embedded tissue specimens were collected from 732 representative cases, diagnosed through December 31, 2002. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI). Among alcohol consumers, the median intake (range) was 3.4 (0.9–292.8) g/d. Compared with nonconsumers, alcohol intake levels of 3.4 g/d or less (RR = 1.00; 95% CI, 0.86–1.15) and more than 3.4 g/d (RR = 1.06; 95% CI, 0.91–1.24) were not significantly associated with overall CRC risk. Analyses based on alcohol intake levels of 30 g/d or less and more than 30 g/d or quartile distributions yielded similar risk estimates. Null associations were also observed between each alcohol intake level and the MSI-, CIMP- or, BRAF-defined CRC subtypes (P &gt; 0.05 for each comparison). These data do not support an adverse effect from alcohol intake on CRC risk, overall or by specific molecularly defined subtypes, among older women. Cancer Prev Res; 4(12); 2035–43. ©2011 AACR.

Negative-feedback (inhibitory) and positive-feedforward (stimulatory) processes regulate physiological systems. Whether such processes are themselves rhythmic is not known. Here, we apply cross-approximate entropy (cross-ApEn), a noninvasive measurement of joint (pairwise) signal synchrony, to inferentially assess hypothesized circadian and ultradian variations in feedback coupling. The data comprised simultaneous measurements of three pituitary and one peripheral hormone (LH, FSH, prolactin, and testosterone) in 12 healthy men each sampled every 10 min for 4 days (5,760 min). Ergodicity, due to the time series stationarity of the measurements over the 4 days, allows for effective estimation of parameters based upon the 12 subjects. Cross-ApEn changes were quantified via moving-window estimates applied to 4-day time series pairs. The resultant ordered windowed cross-ApEn series (in time) were subjected to power spectrum analysis. Rhythmicity was assessed against the null hypothesis of randomness using 1,000 simulated periodograms derived by shuffling the interpulse-interval hormone-concentration segments and redoing cross-ApEn windows and spectral analysis. By forward cross-ApEn analysis, paired LH-testosterone, LH-prolactin, and LH-FSH synchrony maintained dominant rhythms with periodicities of 18–22.5, 18, and 22.5 h, respectively (each P < 0.001). By reverse (feedback) cross-ApEn analysis, testosterone-LH, testosterone-prolactin, and testosterone-FSH synchrony cycles were 30, 18, and 30–45 h, respectively (each P ≤ 0.001). Significant 8- or 24-h rhythms were also detected in most linkages, and maximal bihormonal synchrony occurred consistently at ∼0400–0500. Collectively, these analyses demonstrate significant ultradian (<24 h), circadian (∼24 h), and infradian (>24 h) oscillations in pituitary-testis synchrony, wherein maximal biglandular coordination is strongly constrained to the early morning hours.