A biphasic model of limb venous compliance: a comparison with linear and exponential models.

Compliance is not linear within the physiological range of pressures, and linear modeling may not describe venous physiology adequately. Forearm and calf venous compliance were assessed in nine subjects. Venous compliance was modeled by using a biphasic model with high- and low-pressure linear phases separated by a breakpoint. This model was compared with a linear model and several exponential models. The biphasic, linear, and two-parameter exponential models best represented the data. The mean coefficient of determination for the biphasic model was greater than for the linear and exponential models in the calf (biphasic 0.94 +/- 0.04, exponential 0.81 +/- 0.16, P = not significant; and linear 0.54 +/- 0.05, P < 0.05) and forearm (biphasic 0.83 +/- 0.17, exponential 0.79 +/- 0.15, P = not significant; and linear 0.51 +/- 0.06, P < 0.05). The breakpoint pressure in the biphasic model was higher in the calf than the forearm, 34.4 +/- 3.9 vs. 29.1 +/- 4.5 mmHg, P < 0.05. A biphasic model can describe limb venous compliance and delineate differences in venous physiology at high and low pressures. The steep low-pressure phase of the compliance curve extends to higher pressures in the calf than in the forearm, thereby enlarging the range of pressures over which hemodynamic regulation by the calf venous circulation occurs.     

Tuning of electron delocalization in polynuclear mixed-valence clusters by super-exchange and double exchange

 Values for the exchange-coupling constant J and the double-exchange parameter B have been estimated for dimeric and hexameric mixed-valence iron clusters. For sulfur-bridged species the range of J values is 300–450 cm^–1, and B values vary between 320 and 400 cm^–1. For an OH-bridged diiron cluster B is as large as 1300 cm^–1. Received and accepted: 23 January 1996     

The effects of normalization method on antagonistic activity patterns during eccentric and concentric isokinetic knee extension and flexion

The purpose of this study was to compare different normalization methods of electromyographic (EMG) activity of antagonists during isokinetic eccentric and concentric knee movements. Twelve women performed three maximum knee extensions and flexions isometrically and at isokinetic concentric and eccentric angular velocities of 30 °·s⁻¹, 90 °·s⁻¹, 120 °·s⁻¹ and 150 °·s⁻¹. The EMG activity of the vastus lateralis, rectus femoris, vastus medialis and hamstrings was recorded. The antagonist integrated IEMG values were normalized relative to the EMG of the same muscle during an isometric maximal action (static method). The values were also expressed as a percentage of the EMG activity of the same muscle, at the same angle, angular velocity and muscle action (dynamic method) when the muscle was acting as an agonist. Three-way analysis of variance (ANOVA) designs indicated significantly greater IEMG normalized with the dynamic method compared to the EMG derived using the static method (P < 0.05). These differences were more evident at concentric angular velocities and at the first and last 20 ° of the movement. The present findings demonstrate that the method of normalization significantly influences the conclusions on antagonistic activity during isokinetic maximum voluntary efforts. The dynamic method of normalization is more appropriate because it considers the effects of muscle action, muscle length and angular velocity on antagonist IEMG.     

Glycerol accumulation and water content in larvae of Limenitis archippus: Their importance to winter survival

Half-grown (third instar) larvae of the viceroy butterfly enter facultative winter diapause in response to short-day photoperiod after constructing tubular silk hibernacula in the basal portions of partly eaten willow leaves. Larval water content soon decreases from 80% to about 55%. No detectable quantities of glycerol occur in diapausing larvae maintained at room temperature. Subjection to cold and freezing temperatures causes high levels of glycerol to accumulate (up to 1.9 M or 7.8 g%) within the larvae. These metabolic changes probably lower the supercooling points of the larval fluids and retard both nucleative and inoculative freezing. Diapause termination is not photoperiod dependent, but involves an increase in water content and glycerol breakdown. An unidentified enzyme possibly removes the phosphate group from α-glycerophosphate, thus forming glycerol in the diapausing larvae.     

Rare causes of scoliosis and spine deformity: experience and particular features

Background

Spine deformity can be idiopathic (more than 80% of cases), neuromuscular, congenital or neurofibromatosis-related. However, there are many disorders that may also be involved. We present our experience treating patients with scoliosis or other spine deformities related to rare clinical entities.

Methods

A retrospective study of the records of a school-screening study in North-West Greece was performed, covering a 10-year period (1992–2002). The records were searched for patients with deformities related to rare disorders. These patients were reviewed as regards to characteristics of underlying disorder and spine deformity, treatment and results, complications, intraoperative and anaesthesiologic difficulties particular to each case.

Results

In 13 cases, the spine deformity presented in relation to rare disorders. The underlying disorder was rare neurological disease in 2 cases (Rett syndrome, progressive hemidystonia), muscular disorders (facioscapulohumeral muscular dystrophy, arthrogryposis) in 2 patients, osteogenesis imperfecta in 2 cases, Marfan syndrome, osteopetrosis tarda, spondyloepiphyseal dysplasia congenita, cleidocranial dysplasia and Noonan syndrome in 1 case each. In 2 cases scoliosis was related to other congenital anomalies (phocomelia, blindness). Nine of these patients were surgically treated. Surgery was avoided in 3 patients.

Conclusion

This study illustrates the fact that different disorders are related with curves with different characteristics, different accompanying problems and possible complications. Investigation and understanding of the underlying pathology is an essential part of the clinical evaluation and preoperative work-up, as clinical experience at any specific center is limited.     

Immune Response Gene Expression in Colorectal Cancer Carries Distinct Prognostic Implications According to Tissue,Stage and Site: A Prospective Retrospective Translational Study in the Context of a Hellenic Cooperative Oncology Group Randomised Trial

Background

Although host immune response is an emerging prognostic factor for colorectal cancer, there is no consensus on the optimal methodology, surrogate markers or tissue for study.

Patients and Methods

Tumour blocks were prospectively collected from 344 patients with stage II/III colorectal cancer (CRC) treated with adjuvant chemotherapy. Whole section lymphocytic infiltration was studied along with mRNA expression of CD3Z, CD8, CD4, CXCL9, CXCL13, IGHM, FOXP3, SNAI2 and ESR1 by qRT-qPCR in tissue microarray (TMA) cores from the centre of tumour, invasive margin and adjacent normal mucosa.

Results

Lymphocytic infiltration, deficient MMR (10.9%), KRAS (40.7%) and BRAF (4.9%) mutations or single mRNA gene expression were not prognostic. Tumour ESR1 gene expression (Hazard Ratio [HR] for relapse 2.33, 95% CI 1.35-4.02; HR for death 1.74, 95% CI 1.02-2.97) and absence of necrosis (HR for relapse 1.71, 95% CI 1.05-2.71; HR for death 1.98, 95% CI 1.14-3.43) were adverse prognostic features. We used CD3Z and CD8 expression in order to devise the mRNA-based Immune Score (mIS) and proceeded to partitioning analysis in 267 patients, with age, stage, tumour site (Right vs Left CRC), KRAS mutation and tumour mIS as input factors. Only in patients with stage III right-sided colon cancer, a low immune response was associated with inferior disease-free survival (mIS-low, HR for relapse 2.28, 95% CI 1.05-8.02). No prognostic significance was seen for tumour mIS in any other stage or site of CRC, or for a similar mIS score derived from adjacent normal mucosa. Independent adverse prognostic significance was retained in multivariable analysis for absence of necrosis, tumour ESR1 expression in all patients and low tumour mIS in stage III right-sided CRC.

Conclusions

In localised CRC, mRNA-based CD3Z/CD8 profiling of tumour immune response may have stage, site and tissue-specific prognostic significance, along with ESR1 expression.

Trial Registration

ANZCTR.org.au ACTRN12610000509066     

C-Terminal Fragment of Agrin (CAF): A Novel Marker for Progression of Kidney Disease in Type 2 Diabetics

Background

Diabetes is the leading cause of CKD in the developed world. C-terminal fragment of agrin (CAF) is a novel kidney function and injury biomarker. We investigated whether serum CAF predicts progression of kidney disease in type 2 diabetics.

Methods

Serum CAF levels were measured in 71 elderly patients with diabetic nephropathy using a newly developed commercial ELISA kit (Neurotune®). Estimated glomerular filtration rate (eGFR) and proteinuria in spot urine were assessed at baseline and after 12 months follow up. The presence of end stage renal disease (ESRD) was evaluated after 24 months follow-up. Correlation and logistic regression analyses were carried out to explore the associations of serum CAF levels with GFR, proteinuria, GFR loss and incident ESRD. Renal handling of CAF was tested in neurotrypsin-deficient mice injected with recombinant CAF.

Results

We found a strong association of serum CAF levels with eGFR and a direct association with proteinuria both at baseline (r = 0.698, p<0.001 and r = 0. 287, p = 0.02) as well as after 12 months follow-up (r = 0.677, p<0.001 and r = 0.449, p<0.001), respectively. Furthermore, in multivariate analysis, serum CAF levels predicted eGFR decline at 12 months follow-up after adjusting for known risk factors (eGFR, baseline proteinuria) [OR (95%CI) = 4.2 (1.2–14.5), p = 0.024]. In mice, injected CAF was detected in endocytic vesicles of the proximal tubule.

Conclusion

Serum CAF levels reflect renal function and are highly associated with eGFR and proteinuria at several time points. Serum CAF was able to predict subsequent loss of renal function irrespective of baseline proteinuria in diabetic nephropathy. CAF is likely removed from circulation by glomerular filtration and subsequent endocytosis in the proximal tubule. These findings may open new possibilities for clinical trial design, since serum CAF levels may be used as a selection tool to monitor kidney function in high-risk patients with diabetic nephropathy.     

The effect of interval training in children with exercise-induced asthma competing in soccer

A lot of emphasis has been placed in screening individuals with exercise-induced bronchospasm in order to avoid persistence bronchial hyperactivity and consequent chronic silent inflammation of the respiratory tract. The purpose of this study was to evaluate the effect of interval training on the respiratory function and endurance in children with exercise-induced asthma (EIA) participating in the sport of soccer. Twenty-nine boys ages 10-14, who developed EIA after a 6-minute free running test (decline in forced expiratory volume in 1 second: FEV(1)10%), participated in the study. They were divided into 2 groups (experimental: n = 18, and control: n = 11), fulfilling the same criteria (i.e., age, body height and weight, and severity of asthma). The experimental group exercised with the interval training method for a period of 8 weeks, (3 sessions per week), whereas the control group exercised with the usual football program. Measurements were made for FEV(1) and endurance in both groups, before and after the application of training (8 weeks). Following the implementation of the training program, a significant improvement in FEV(1) and endurance was documented in the experimental group, as well as significant differences between the 2 groups. In conclusion, duration and aerobic training via the interval method seems to be beneficial to soccer players with EIA.     

Dynamic Motions of the HIV-1 Frameshift Site RNA

The HIV-1 frameshift site (FS) plays a critical role in viral replication. During translation, the HIV-1 FS transitions from a 3-helix to a 2-helix junction RNA secondary structure. The 2-helix junction structure contains a GGA bulge, and purine-rich bulges are common motifs in RNA secondary structure. Here, we investigate the dynamics of the HIV-1 FS 2-helix junction RNA. Interhelical motions were studied under different ionic conditions using NMR order tensor analysis of residual dipolar couplings. In 150 mM potassium, the RNA adopts a 43°(±4°) interhelical bend angle (β) and displays large amplitude, anisotropic interhelical motions characterized by a 0.52(±0.04) internal generalized degree of order (GDO_int) and distinct order tensor asymmetries for its two helices (η = 0.26(±0.04) and 0.5(±0.1)). These motions are effectively quenched by addition of 2 mM magnesium (GDO_int = 0.87(±0.06)), which promotes a near-coaxial conformation (β = 15°(±6°)) of the two helices. Base stacking in the bulge was investigated using the fluorescent purine analog 2-aminopurine. These results indicate that magnesium stabilizes extrahelical conformations of the bulge nucleotides, thereby promoting coaxial stacking of helices. These results are highly similar to previous studies of the HIV transactivation response RNA, despite a complete lack of sequence similarity between the two RNAs. Thus, the conformational space of these RNAs is largely determined by the topology of their interhelical junctions.     

Variants of the human PPARG locus and the susceptibility to chronic periodontitis

Apart from its regulatory function in lipid and glucose metabolism, peroxisome proliferator-activated receptor (PPAR)γ has impact on the regulation of inflammation and bone metabolism. The aim of the study was to investigate the association of five polymorphisms (rs10865710, rs2067819, rs3892175, rs1801282, rs3856806) within the PPARG gene with chronic periodontitis. The study population comprised 402 periodontitis patients and 793 healthy individuals. Genotyping of the PPARG gene polymorphisms was performed by PCR and melting curve analysis. Comparison of frequency distribution of genotypes between individuals with periodontal disease and healthy controls for the polymorphism rs3856806 showed a P-value of 0.04 but failed to reach significance after correction for multiple testing (P??0.90). A 3-site analysis (rs2067819-rs1801282-rs3856860) revealed five haplotypes with a frequency of ≥1% among cases and controls. Following adjustment for age, gender and smoking, none of the haplotypes was significantly different between periodontitis and healthy controls after Bonferroni correction. This study could not show a significant association between PPARG gene variants and chronic periodontitis.