Amiodarone Decreases Plasma Brain Natriuretic Peptide Level in Patients with Heart Failure and Ventricular Tachyarrhythmia

Brain natriuretic peptide (BNP) is a powerful neurohormonal marker of left ventricular function and prognosis. Amiodarone either has no effect or improves the haemodynamics in patients with left ventricular dysfunction, but its effect on BNP is unknown. This study evaluated the effect of amiodarone on plasma BNP level in patients with heart failure and ventricular tachyarrhythmia.Plasma BNP level was studied in 46 patients with heart failure ventricular tachyarrhythmia, before (baseline) and at week 2 and months 1, 3 and 6 of amiodarone treatment. In addition, 21 patients with heart failure and ventricular tachyarrhythmia, who received an implantable cardioverter defibrillator, but not amiodarone, were studied on the same schedule. All patients had previously received potent vasodilator and beta-blocker therapy. Echocardiography and Holter monitoring were also performed.Amiodarone significantly decreased plasma BNP levels at week 2 to month 6 during therapy. Heart rates and frequencies of premature ventricular complexes were markedly reduced by amiodarone. Echocardiographic findings did not show a change in left ventricular end-diastolic dimensions, despite a slight increase in fraction shortening at month 6 during amiodarone therapy. The above parameters showed no change in patients without amiodarone. The effect of heart rate, premature ventricular complexes, fraction shortening, serum creatinine or thyroid stimulating hormone level was not significantly associated with decrease in BNP level during amiodarone therapy by a multivariate analysis. Among amiodarone-treated patients, mortality was higher in 24 with BNP levels 100 pg/ml at month 6 than in 22 with BNP levels <100 pg/ml during a mean follow-up period of 31 months.Amiodarone appears to have a decreasing effect on plasma BNP level, as well as an antiarrhythmic effect, in patients with heart failure and ventricular tachyarrhythmia.     

Two cortical mechanisms support the integration of visual and auditory speech: A hypothesis and preliminary data

Visual speech (lip-reading) influences the perception of heard speech. The literature suggests at least two possible mechanisms for this influence: “direct” sensory–sensory interaction, whereby sensory signals from auditory and visual modalities are integrated directly, likely in the superior temporal sulcus, and “indirect” sensory–motor interaction, whereby visual speech is first mapped onto motor-speech representations in the frontal lobe, which in turn influences sensory perception via sensory–motor integration networks. We hypothesize that both mechanisms exist, and further that previous demonstrations of lip-reading functional activations in Broca's region and the posterior planum temporale reflect the sensory–motor mechanism. We tested one prediction of this hypothesis using fMRI. We assessed whether viewing visual speech (contrasted with facial gestures) activates the same network as a speech sensory–motor integration task (listen to and then silently rehearse speech). Both tasks activated locations within Broca's area, dorsal premotor cortex, and the posterior planum temporal (Spt), and focal regions of the STS, all of which have previously been implicated in sensory–motor integration for speech. This finding is consistent with the view that visual speech influences heard speech via sensory–motor networks. Lip-reading also activated a much wider network in the superior temporal lobe than the sensory–motor task, possibly reflecting a more direct cross-sensory integration network.     

Cigarette smoking and the risk of colorectal cancer among men: a prospective study in Japan.

The association between cigarette smoking and the risk of colorectal cancer remains controversial. We examined this association using a population-based prospective cohort study in Miyagi, Japan. In 1990, we delivered a self-administered questionnaire on cigarette smoking and other health habits to 25 279 men who were 40-64 years of age and lived in 14 municipalities of Miyagi Prefecture. A total of 22 836 men responded (90.3% response rate). During 7 years of follow-up (158 376 person-years), we identified 188 patients of colorectal cancer. Relative risks and 95% confidence intervals were estimated by the Cox proportional-hazards regression analysis with adjustment for potential confounders. The multivariate-adjusted relative risks (95% confidence interval) of colorectal cancer for past smokers and current smokers compared with those who had never smoked were 1.73 (1.04-2.87) and 1.47 (0.93-2.34), respectively. Among current smokers, both a higher number of cigarettes smoked per day and an earlier age at which smoking had started were associated with a significant linear increase in risk (P for trend <0.05). Our findings are consistent with the hypothesis that cigarette smoking is associated with a higher risk of colorectal cancer in men.     

Urinary trypsin inhibitor suppresses premature cervical ripening

Unknown signals from the fetus are thought to be involved in the onset of parturition. We recently discovered that urinary trypsin inhibitor (UTI) from fetal urine inhibits uterine muscle contraction. Objectives: The aim of this research was to elucidate the mechanism of action of UTI in suppressing cervical maturation. Study design: Non-pregnant and pregnant rabbits pretreated with and without UTI suppositories containing 1000 U (400 μg) for 3 days were treated for 2 days with vaginal suppositories containing 100 ng of interleukin-8 (IL-8). Results: IL-8 induced softening and dilatation of the rabbit cervices. In contrast UTI inhibited IL-8 induced cervical softening and dilatation. Water content, collagen content, neutrophil counts, elastase activity and collagenase activity of the cervix were increased by IL-8, but they did not increase by IL-8 with UTI. Conclusion: These results suggest that UTI inhibits cervical maturation induced by IL-8.     

Transforming growth factor-beta-1 latency-associated peptide and soluble betaglycan prevent a glucose-induced increase in fibronectin production in cultured human mesangial cells

This study was performed to investigate the effects of transforming growth factor-beta1 (TGF-beta1) latency-associated peptide (LAP) and betaglycan on TGF-beta1 activity, and on the glucose-induced overproduction of fibronectin in cultured human mesangial cells (MCs). We found that recombinant LAP and recombinant soluble betaglycan decrease the active form of TGF-beta1, measured by ELISA, in a dose-dependent manner in a cell-free system. The effective dosages of LAP and soluble betaglycan for a 50% reduction were approximately 20- and 75-fold of the TGF-beta1 concentration, respectively. The active form of TGF-beta1 in the media secreted from MCs was significantly (p < 0.01) reduced by the addition of 10 nmol/l LAP and 10 nmol/l soluble betaglycan with no significant change in total (active + latent) TGF-beta1. Recombinant LAP and soluble betaglycan also inhibited a recombinant TGF-beta1-stimulated increase in fibronectin production in MCs. Furthermore, the glucose-induced increase in fibronectin secreted from MCs was significantly (p < 0.01) suppressed by concomitant incubation with LAP or soluble betaglycan, while these agents had no effect on fibronectin production under physiological glucose concentrations. These results indicate that recombinant LAP and soluble betaglycan suppress the glucose-induced overproduction of fibronectin presumably via inhibition of TGF-beta1 activity in MCs. Further in vivo studies are needed to define the possible beneficial effects of these agents in diabetic nephropathy.     

Convergence of selected inputs from sensory afferents to trigeminal premotor neurons with possible projections to masseter motoneurons in the rabbit

Peripheral input convergence on trigeminal premotor neurons in the vicinity of trigeminal motor nucleus has been investigated. Thirty neurons were identified by their antidromic responses to microstimulation of the masseteric subnucleus of trigeminal motor nucleus (NVmot-mass). Peripheral receptive fields were found in the buccal mucosae, periodontal ligaments, palate, tongue and vibrissae for 16 neurons located in the intertrigeminal area (NVint), supratrigeminal area (NVs), main sensory trigeminal nucleus (NVsnpr) and subnucleus gamma of the oral nucleus of the spinal trigeminal tract (NVspo-gamma). Eleven neurons in the NVint, NVs and NVspo-gamma responded to passive jaw opening: nine neurons were activated and two were inhibited. None of the neurons responded to both the orofacial mechanical stimulation and passive jaw opening. Forty-six percent of neurons (13 out of 28 tested) received inputs from the inferior alveolar nerve (IAN) and 53% of neurons (8 out of 15 tested) received inputs from the infraorbital nerve (ION). Out of 15 neurons tested for inputs from the IAN and ION, 7 neurons in the NVsnpr and NVspo-gamma received input from both. Sixteen percent of neurons (4 out of 25) received inputs from the masseteric nerve (MassN). None of the neurons with inputs from IAN and/or ION also received inputs from the MassN. We suggest that trigeminal premotor interneurons with projections to the NVmot-mass fall into two broad categories, those with inputs from the IAN and/or ION and those with inputs from the MassN, possibly muscle spindle afferents, and no neuron receiving inputs from both.     

Spatial reference and standing posture during high-speed Coriolis stimulation

BACKGROUND: In a previous study, we found that sensation, gaze, and posture during Coriolis stimulation differ considerably between vision and nonvision conditions during rotations at 60 degrees x s(-1). To determine the validity of these findings at higher velocities, we compared standing postures during Coriolis stimulation up to 150 degrees x s(-1) between vision and nonvision conditions. METHODS: The 19 subjects underwent 5-min rotation tests at 50 to 150 degrees x s(-1). While standing on a force platform attached to a rotating device, each subject tilted his or her head and then returned it to upright, first with the eyes covered, then with eyes open. Six subjects were re-examined 5 d later after 4 consecutive days of 20-min rotations with their eyes open. We assessed success and failure to stand and recorded the center of pressure during rotation. RESULTS: Although success rates (number of successes/19) differed between vision and nonvision conditions at 50 degrees x s(-1) (94.7% vs. 57.9%), they steeply decreased as rotation velocity increased and showed no difference at 70 degrees x s(-1) and faster velocities. After the 4-d exposure, however, subjects could stand at higher velocities particularly under the vision condition. A patient with bilateral labyrinthine loss, being examined for reference, could stand at 110 degrees x s(-1) even with the eyes covered. CONCLUSIONS: Untrained subjects frequently fell during high-speed Coriolis stimulation, apparently because vision was insufficient to provide a spatial reference frame from the stationary surroundings. Following rotation training with their eyes open, subjects appeared more able to use the visual reference frame and falls were reduced.