A comparison of true and premodulated interferential currents

OBJECTIVE: To compare true and premodulated interferential currents (IFCs) in terms of sensory, motor, and pain thresholds; maximum electrically induced torque (MEIT); and comfort. DESIGN: Repeated-measures design. SETTING: Laboratory setting. PARTICIPANTS: University student and staff volunteers. INTERVENTIONS: Participants were exposed to 4 different conditions, chosen to evaluate 2 fundamental differences between true and premodulated IFCs. The conditions were different combinations of (1) premodulated or constant-amplitude currents applied at the skin and (2) crossed or parallel current paths. MAIN OUTCOME MEASURES: Sensory, motor, and pain thresholds; MEIT; and subjective reports of relative discomfort were recorded for each of the 4 conditions. Motor to sensory threshold ratios were subsequently calculated to assess depth efficiency of stimulation. RESULTS: The major findings were that crossed currents (true IFC) had no advantage over parallel currents (premodulated IFC) in terms of motor to sensory threshold ratio, MEIT, or comfort, and that premodulated currents produced higher torque values and less discomfort than constant-amplitude currents (true IFC). These results contradict the claimed superiority of true IFC. CONCLUSIONS: The findings indicate that premodulated IFC, delivered via 2 large electrodes, may be clinically more effective than the traditional true IFC arrangement in terms of depth efficiency, torque production, and patient comfort.     

Monophasic and biphasic stimulation evoke different responses

In 31 subjects, psychophysiological sensory perception threshold and the waveform of orthodromic sensory nerve action potentials (SNAPs) produced by constant-current 100-micros monophasic negative pulses were compared to those produced by biphasic (negative-positive) symmetrical pulses (100-micros per phase). In addition, the effects of 200-micros monophasic negative pulses were studied. Graded stimuli were delivered to the index finger, and SNAPs were recorded over the median nerve at the wrist. Perception threshold was significantly different among the three conditions. Furthermore, in 26 subjects, at the lower intensities at which SNAPs first appeared, the evoked potential waveform had two small negative phases with biphasic stimuli, but a single negative phase in response to monophasic pulses. At higher stimulus intensities, all SNAPs had a single large negative phase regardless of the stimulus. These perception and waveform findings suggest that, contrary to historical belief, the trailing positive phase of a biphasic pulse has a stimulating effect at low stimulus intensities.     

Genetic liability of type 1 diabetes and the onset age among 22,650 young Finnish twin pairs: a nationwide follow-up study

Finland has the world's highest incidence of type 1 diabetes, and it is steadily increasing. We determined concordance rates and estimated heritability for type 1 diabetes in the Finnish Twin Cohort, a population-based twin cohort of 22,650 twin pairs. In addition, we studied age of onset in the first affected twin and discordance time between concordant twin pairs. Finnish twins born between 1958 and 1986 were followed for type 1 diabetes until 1998. We identified 228 twin pairs with type 1 diabetes: 44 monozygotic (MZ), 183 dizygotic (DZ), and 1 pair with unknown zygosity. The pairwise concordance for type 1 diabetes was 27.3% (95% CI 22.8-31.8) in MZ and 3.8% (2.7-4.9) in DZ twins. The probandwise concordance was 42.9% (26.7-59.2) and 7.4% (2.2-12.6), respectively. The longest discordance times were 6.9 years among concordant MZ twins and 23.6 years among DZ twins. The risk for type 1 diabetes was highest in cotwins of the index twins diagnosed at a very young age. The model with additive genetic and individual environmental effects was the best-fitting liability model, with 88% of phenotypic variance due to genetic factors and the remaining variance due to unshared environmental factors. In conclusion, these nationwide twin data demonstrated high genetic liability for type 1 diabetes. Early-onset diabetes increases the risk in cotwins. However, the majority of affected MZ twin pairs remain discordant for type 1 diabetes.     

Pharmacological characterization of ketotifen effects on guinea pig ileum

The effects of Ketotifen (Ke) on the contraction of isolated guinea pig ileum induced by electrical stimulation, nicotine or acetylcholine have been investigated. Ke (10(-6)-10(-5) M) inhibited electrically-induced contractions. Prostaglandin F2 alpha, when added to the bath shortly after Ke, reversed this effect. Furthermore, Ke significantly inhibits guinea pig ileum contractions induced by nicotine and acetylcholine both on innervated and denervated ileal strips. These results suggest that Ke influence on ileum contractions is mediated either by inhibition of acetylcholine release from postganglionic parasympathetic fibres of ileum or by anticholinergic effect (atropine-like action). The inhibitory effect of Ke against acetylcholine-induced contractions is in favor of the latter possibility, although nonspecific membrane stabilizing effect might be also involved in the mode of Ke action.     

Subarachnoid Hemorrhage in Type 1 Diabetes: A prospective cohort study of 4,083 patients with diabetes

OBJECTIVE

To estimate for the first time the incidence of subarachnoid hemorrhage (SAH) in type 1 diabetes.

RESEARCH DESIGN AND METHODS

Using the nationwide Finnish Diabetic Nephropathy (FinnDiane) Study cohort of 4,083 patients with type 1 diabetes (mean age of 37.4 ± 11.8 years at enrollment), we analyzed the incidence of first-ever SAH events.

RESULTS

During the follow-up time of 36,680 person-years (median 9.4 years), 15 patients with type 1 diabetes experienced an aneurysmal or nonaneurysmal SAH, and thus the crude incidence of SAH was 40.9 (95% CI 22.9–67.4) per 100,000 person-years. One patient had a verified aneurysmal SAH, and four patients died suddenly of an SAH, which was most likely caused by an aneurysm. SAHs in 10 out of 15 patients were classified as nonaneurysmal SAH, and thus the crude incidence of nonaneurysmal SAH was 27.3 (13.1–50.1) per 100,000 person-years. None of the nonaneurysmal SAHs were fatal. In univariate analysis, current smokers had a hazard ratio of 4.82 (95% CI 1.31–17.81) for nonaneurysmal SAH.

CONCLUSIONS

The incidence of nonaneurysmal SAH is high among patients with type 1 diabetes. Our findings suggest that nonaneurysmal SAH is a distinct new microvascular complication in type 1 diabetes.Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular event, which is usually caused by a rupture of a cerebrovascular aneurysm. These aneurysms are mostly found in relatively large-caliber (≥1 mm) vessels and can often be considered as macrovascular lesions. The overall incidence of SAH has been reported to be 10.3 per 100,000 person-years (1), even though the variation in incidence between countries is substantial (1). Notably, the population-based incidence of SAH is 35 per 100,000 person-years in the adult (≥25 years of age) Finnish population (2). The incidence of nonaneurysmal SAH is globally unknown, but it is commonly believed that 5–15% of all SAHs are of nonaneurysmal origin. Prospective, long-term, population-based SAH risk factor studies suggest that smoking (2–4), high blood pressure (2–4), age (2,3), and female sex (2,4) are the most important risk factors for SAH, whereas diabetes (both types 1 and 2) does not appear to be associated with an increased risk of SAH (2,3).An increased risk of cardiovascular disease is well recognized in people with diabetes. There are, however, very few studies on the risk of cerebrovascular disease in type 1 diabetes since most studies have focused on type 2 diabetes alone or together with type 1 diabetes. Cerebrovascular mortality in the 20–39-year age-group of people with type 1 diabetes is increased five- to sevenfold in comparison with the general population but accounts only for 15% of all cardiovascular deaths (5). Of the cerebrovascular deaths in patients with type 1 diabetes, 23% are due to hemorrhagic strokes (5). However, the incidence of SAH in type 1 diabetes is unknown.By knowing the incidence of SAH in type 1 diabetes, the overall risk of stroke in patients with type 1 diabetes could be estimated more accurately. Moreover, comprehensive prospective patient cohorts that are susceptible to cerebrovascular events may provide new knowledge of the risk factors for SAH. In this prospective cohort study of 4,083 patients with type 1 diabetes, we aimed to determine the incidence and characteristics of SAH.     

Effect of lysed and non-lysed sickle red cells on the activation of NLRP3 inflammasome and LTB4 production by mononuclear cells

Objective and design

This study tested the hypothesis that sickle red blood cell (SS-RBC) can induce inflammasome NLRP3 components gene expression in peripheral blood mononuclear cells (PBMCs) as well as interleukin-1β (IL-1β) and leukotriene B4 (LTB4) production. Additionally, we investigated the effect of hydroxyurea (HU) treatment in these inflammatory markers.

Methods

PBMCs from healthy donors (AA-PBMC) were challenged with intact and lysed RBCs from SCA patients (SS-RBC) and from healthy volunteers (AA-RBC). NLRP3, IL-1β, IL-18 and Caspase-1 gene expression levels were assessed by quantitative PCR (qPCR). IL-1β protein levels and LTB4 were measured by ELISA.

Results

We observed that lysed SS-RBC induced the expression of inflammasome NLRP3 components, but this increase was more prominent for CASP1 and IL18 expression levels. Moreover, we observed that intact SS-RBC induced higher production of IL-1β and LTB4 than lysed SS-RBC. Although SCA patients treated with HU have a reduction in NLRP3 gene expression and LTB4 production, this treatment did not modulate the expression of other inflammasome components or IL-1β production.

Conclusions

Thus, our data suggest that caspase-1, IL-1β and IL-18 may contribute to the inflammatory status observed in SCA and that HU treatment may not interfere in this inflammatory pathway.