Physiological tremor: does handedness make a difference?

The purpose of this study was to quantify with precision the characteristics of normal physiological tremor in the dominant and nondominant hand of a group of right-handed females. Twenty-two right-handed females (aged 20 to 40) gave informed consent to participate. Manual dominance determined with a questionnaire had to be equal to, or above 90%, for subjects to be accepted in the study. While the subjects kept their eyes closed, tremor was recorded simultaneously in the two extended index fingers during 40 s. Preceding the recording of postural tremor there was a period during which the subjects were asked to relax (control condition); to exert a pressure with the two index fingers on two strain gauges (static condition); or to press on and off with both index fingers on two strain gauges (dynamic condition). Each condition was recorded twice with two helium neon velocity lasers. This procedure was repeated after permutation of the lasers, thus a total of twelve sweeps of data were recorded. Seven parameters were used to analyze the tremor signal including measures of harmonicity, median frequency, proportional power in the 7-12 Hz range, amplitude, waveform morphology, entropy, and nonlinearity. Significant differences between hands were found in three parameters (median frequency, power in 7-12 Hz and entropy) but not in tremor amplitude (RMS). In addition, significant differences were found in five out of seven characteristics between conditions. These results suggest that neuromotor activity preceding the recording of tremor has a significant influence on tremor characteristics and that some of these characteristics are significantly different between the right and left hand in right-handed females.     

Cyclophosphamide-induced cystitis in freely-moving conscious rats: behavioral approach to a new model of visceral pain

PURPOSE: To develop a model of visceral pain in rats using a behavioral approach. Cyclophosphamide (CP), an antitumoral agent known to produce toxic effects on the bladder wall through its main toxic metabolite acrolein, was used to induce cystitis. MATERIALS AND METHODS: CP was administered at doses of 50, 100 and 200 mg./kg. i.p. to male rats, and their behavior observed and scored. The effects of morphine (0.5 to 4 mg./kg. i.v.) on CP-induced behavioral modifications were tested administered alone and after naloxone (1 mg./kg. s.c.). In addition, 90 minutes after CP injection, that is, at the time of administration of morphine, the bladder was removed in some rats for histological examination. Finally, to show that the bladder is essential for the CP-induced behavioral modifications, female rats also received CP at doses of 200 mg./kg. i.p. and of 20 mg. by the intravesical route, and acrolein at doses of 0.5 mg. by the intravesical route and of 5 mg./kg. i.v. RESULTS: CP dose-relatedly induced marked behavioral modifications in male rats: breathing rate decrease, closing of the eyes and occurrence of specific postures. Morphine dose-dependently reversed these behavioral disorders. A dose of 0.5 mg./kg. produced a reduction of almost 50% of the behavioral score induced by CP 200 mg./kg. This effect was completely prevented by pretreatment with naloxone. At the time of administration of morphine, histological modifications of the bladder wall, such as chorionic and muscle layer edema, were observed. In female rats, CP 200 mg./kg. i.p. produced the same marked behavioral modifications as those observed in male rats. Administered at the dose of 20 mg. intravesically, CP did not produce any behavioral effects, whereas acrolein at 0.5 mg. intravesically induced behavioral modifications identical to those under CP 200 mg./kg. i.p., with the same maximal levels. Conversely, acrolein 5 mg./kg. i.v. did not produce any behavioral effects at all. CONCLUSIONS: Overall, these results indicate that this experimental model of CP-induced cystitis may be an interesting new behavioral model of inflammatory visceral pain, allowing a better understanding of these painful syndromes and thus a better therapeutic approach to them.     

Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications.

PURPOSE: It has been hypothesized that tumors with high interstitial fluid pressure (IFP) and/or hypoxia respond poorly to chemotherapy (CT) because of poor drug delivery. Preclinical studies have shown that paclitaxel reduces the IFP and improves the oxygenation (pO(2)) of tumors. Our aim is to evaluate the IFP and pO(2) before and after neoadjuvant CT using sequential paclitaxel and doxorubicin in patients with breast cancer tumors of >/= 3 cm. PATIENTS AND METHODS: Patients were randomly assigned, according to an institutional review board-approved phase II protocol, to receive neoadjuvant sequential CT consisting of either four cycles of dose-dense doxorubicin at 60 mg/m(2) every 2 weeks followed by nine cycles of weekly paclitaxel at 80 mg/m(2) (group 1) or vice versa, with paclitaxel administered before doxorubicin (group 2). Patients were re-evaluated clinically and radiologically. The IFP (wick-in-needle technique) and pO(2) (Eppendorf) were measured in tumors at baseline and after completing the administration of the first and second drug. RESULTS: IFP and pO(2) were measured in 54 patients at baseline and after the first CT. Twenty-nine and 25 patients were randomly assigned to groups 1 and 2, respectively. Paclitaxel, when administered first, decreased the mean IFP by 36% (P = .02) and improved the tumor pO(2) by almost 100% (P = .003). In contrast, doxorubicin did not have a significant effect on either parameter. This difference was independent of the tumor size or response measured by ultrasound. CONCLUSION: Paclitaxel significantly decreased the IFP and increased the pO(2), whereas doxorubicin did not cause any significant changes. Tumor physiology could potentially be used to optimize the sequence of neoadjuvant CT in breast cancer.     

Hepatitis C Testing,Status and Treatment among Marginalized People Who Use Drugs in an Inner City Setting: An Observational Cohort Study

Background: Chronic hepatitis C virus (HCV) infection is common among people who inject drugs (PWID) and is associated with morbidity and premature death. Although HCV can be cured, treatment may be inaccessible. We studied HCV testing, status and treatment among marginalized people who use drugs in Ottawa, Canada, a setting with universal insurance coverage for physician services.

Methods: We analyzed data from the Participatory Research in Ottawa: Understanding Drugs study, a cross-sectional, peer-administered survey of people who use drugs from 2012 to 2013. We linked responses to population-based health administrative databases and used multivariable Poisson regression to identify factors independently associated with self-reported HCV testing, self-reported positive HCV status, and database-determined engagement in HCV treatment. Results: Among 663 participants, 562 (84.8%) reported testing for HCV and 258 (45.9%) reported HCV-positive status. In multivariable analysis, HCV-positive status was associated with female gender (RR 1.27; 95%CI 1.04 to 1.55), advancing age (RR 1.03/year; 95%CI 1.02 to 1.04), receiving disability payments (RR 1.42; 95%CI 1.06 to 1.91), injecting drugs (RR 5.11; 95%CI 2.64 to 9.91), ever injecting with a used needle (RR 1.30; 95%CI 1.12 to 1.52), and ever having taken methadone (RR 1.26; 95%CI 1.05 to 1.52). Of HCV positive participants, 196 (76%) were engaged in primary care but only 23 (8.9%) had received HCV therapy. Conclusions/Importance: Although HCV testing and positive status rates are high among PWID in our study, few have received HCV treatment. Innovative initiatives to increase access to HCV treatment for PWID are urgently needed.     

The relationship between serum sodium and intracranial pressure when using hypertonic saline to target mild hypernatremia in patients with head trauma

During sepsis, the liver plays a key role. It is implicated in the host response, participating in the clearance of the infectious agents/products. Sepsis also induces liver damage through hemodynamic alterations or through direct or indirect assault on the hepatocytes or through both. Accordingly, liver dysfunction induced by sepsis is recognized as one of the components that contribute to the severity of the disease. Nevertheless, the incidence of liver dysfunction remains imprecise, probably because current diagnostic tools are lacking, notably those that can detect the early liver insult. In this review, we discuss the epidemiology, diagnostic tools, and impact on outcome as well as the pathophysiological aspects, including the cellular events and clinical picture leading to liver dysfunction. Finally, therapeutic considerations with regard to the weakness of the pertinent specific approach are examined.