Effects of sex and age on strength-duration properties.

OBJECTIVE: To evaluate the possible effects of sex and age on strength-duration time constant (SDTC). METHODS: The SDTC of 126 healthy volunteers was measured following stimulation of right median nerve at the wrist. Variations in values were evaluated according to sex and age. RESULTS: The SDTC was 438.6+/-114.5 micros in women and 396.2+/-90.3 in men (P=.023). In men, as age increased, so did SDTC. However, this was not true in women. Comparing the values of women and men, aged below 40, demonstrated a difference in excitability, confined to younger patients. CONCLUSIONS: As SDTC depends on the biophysical properties of the axonal membrane and can provide some information about Na(+) channel function, these data raise the possibility of a difference in Na(+) channel function between men and women and a difference in the conductance with age. SIGNIFICANCE: The age- and sex-related differences shown in this study suggest a possible biochemical or hormonal influence on axonal excitability.     

The effect of hyperventilation on strength-duration properties in diabetic polyneuropathy.

OBJECTIVE: Hyperventilation and ischaemia increase axonal excitability by changing Na+ conductance in healthy subjects. However, the changes in excitability during and after ischaemia in diabetic patients are less than in healthy controls. This is known as ischaemic resistance. In this study, we investigated the effects of hyperventilation for 20 min on strength-duration time constant (SDTC) of motor axons of the median nerve of diabetic patients with polyneuropathy to determine whether diabetics are less affected by hyperventilation, a form of resistance similar to the ischaemic resistance of diabetics. METHODS: The SDTC of 14 diabetic patients with polyneuropathy and 10 healthy volunteers were measured following stimulation of right median nerve at the wrist prior to and after hyperventilation for 20 min. RESULTS: There was a significant increase in the SDTC in control subjects, but no significant change in the SDTC for patients with diabetic polyneuropathy. The score of the clinical response (paraesthesiae and carpopedal spasm) to hyperventilation of controls was also significantly greater in the controls than the patients. CONCLUSION: Hyperventilation for 20 min has little influence on SDTC in patients with diabetic polyneuropathy. SIGNIFICANCE: The 'resistance' of diabetic nerve is not confined to ischaemia but involves other manoeuvres that can alter axonal excitability.     

Inductively coupled transmission of neuro-active signals: analysis of optimal parameters

Fifteen parameters that play a role in the optimal transmission of therapeutic signals by inductively coupled implantable neurostimulator have been investigated. For this purpose, at first, a model of the system was constructed from which the system transfer function was obtained. Then, the relationship between the transfer gain and each parameter was evaluated using mathematical equations and a specifically built computer program. This study showed that the gain could be increased selecting small values for some parameters (the number of active coil windings, first radii of inner and outer paths of the core, heights of the core base and windings, position under the skin, internal resistances of the active and passive coils, tissue impedance between the contacts of electrode), and high values for the others (the number of passive coil windings, second radii of inner and outer paths of the core, frequency of the signal, relative magnetic permeability of the core). Critical saturation values were another considerable point. The nearest commercially available standard values should be preferred in practical applications.     

Comparison of DNA- and RNA-based methods for detection of truncating BRCA1 mutations

A number of methods are used for mutational analysis of BRCA1, a large multi-exon gene. A comparison was made of five methods to detect mutations generating premature stop codons that are predicted to result in synthesis of a truncated protein in BRCA1. These included four DNA-based methods: two-dimensional gene scanning (TDGS), denaturing high performance liquid chromatography (DHPLC), enzymatic mutation detection (EMD), and single strand conformation polymorphism analysis (SSCP) and an RNA/DNA-based protein truncation test (PTT) with and without complementary 5' sequencing. DNA and RNA samples isolated from 21 coded lymphoblastoid cell line samples were tested. These specimens had previously been analyzed by direct automated DNA sequencing, considered to be the optimum method for mutation detection. The set of 21 cell lines included 14 samples with 13 unique frameshift or nonsense mutations, three samples with two unique splice site mutations, and four samples without deleterious mutations. The present study focused on the detection of protein-truncating mutations, those that have been reported most often to be disease-causing alterations that segregate with cancer in families. PTT with complementary 5' sequencing correctly identified all 15 deleterious mutations. Not surprisingly, the DNA-based techniques did not detect a deletion of exon 22. EMD and DHPLC identified all of the mutations with the exception of the exon 22 deletion. Two mutations were initially missed by TDGS, but could be detected after slight changes in the test design, and five truncating mutations were missed by SSCP. It will continue to be important to use complementary methods for mutational analysis.     

Effects of mTOR inhibitor–related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients

We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow-up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all-cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV-related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk.     

Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry.

There are several genes that code for enzymes, including various forms of superoxide dismutase and glutathione peroxidase, that protect the cell against oxidative damage that, in turn, can lead to carcinogenesis. There are a few common genetic polymorphisms in these genes that lead to altered proteins. Three that have been identified are SOD2 Val-9Ala, GPX1 Pro198Leu, and the GPX1 GCG repeat (three alleles with four, five, or six repeats). The SOD2 variant has been associated with increased breast cancer risk in two studies. The GPX1 variants have not been studied with respect to breast cancer, but Pro198Leu has been associated with lung cancer. We conducted a case-control study of these three polymorphisms in incident, invasive breast cancer in Caucasian women under 55. There were 399 cases and 372 controls genotyped, of whom 488 were premenopausal, 208 postmenopausal, and 75 of unknown menopausal status. We were unable to replicate the previously observed association with SOD2 Val-9Ala and also found no association between breast cancer and GPX1 Pro198Leu. However, the allele of GPX1 containing four GCG repeats was significantly associated with breast cancer risk in premenopausal women (odds ratio, 1.55; 95% confidence interval, 1.04-2.30 for carriers versus noncarriers). There is a significant trend of increasing risk with increasing number of alleles with four GCG repeats (P = 0.03). This variant has not previously been reported to be associated with breast cancer.     

Comparison of subclinical left and right ventricular systolic dysfunction in non-dipper and dipper hypertensives: impact of isovolumic acceleration

Objectives: To evaluate subclinical left ventricular and right ventricular systolic impairment in dipper and non-dipper hypertensives by using isovolumic acceleration.

Methods: About 45 normotensive healthy volunteers (20 men, mean age 43?±?9 years), 45 dipper (27 men, mean age 45?±?9 years) and 45 non-dipper (25 men, 47?±?7 years) hypertensives were enrolled. Isovolumic acceleration was measured by dividing the peak myocardial isovolumic contraction velocity by isovolumic acceleration time.

Results: Non-dippers indicated lower left ventricular (2.2?±?0.4?m/s² versus 2.8?±?1.0?m/s², p?2 versus 3.5?±?1.0?m/s², p?=?0.012) compared with dippers. Left ventricular mass index (p?=?0.001), interventricular septal thickness (p?=?0.002) and myocardial performance index (p?p?=?0.002), mass index (p?=?0.001) and right ventricular myocardial performance index (p?Conclusion: The present study demonstrates that non-dipper hypertensives have increased left and right ventricular subclinical systolic dysfunction compared with dippers. Isovolumic acceleration is the only echocardiographic parameter in predicting this subtle impairment.