Normal intracortical excitability in developmental stuttering.

Persistent developmental stuttering (PDS) shares clinical features with task-specific dystonias. In these dystonias, intracortical inhibition is abnormally weak. We therefore sought to determine intracortical inhibition and intracortical facilitation in PDS. In 18 subjects with PDS since childhood (mean age, 39.4 [SD 13.0] years) and 18 speech-fluent controls (43.6 [14.3] years), we investigated resting and active motor thresholds as well as intracortical inhibition and facilitation of the optimal representation of the abductor digiti minimi of the dominant hand using transcranial magnetic stimulation. In PDS, the resting and active motor thresholds were increased, whereas intracortical inhibition and facilitation were normal. Normal intracortical excitability makes a pathophysiological analogy between focal dystonia and PDS less likely. The enhanced motor threshold suggests reduced motor cortical neuronal membrane excitability in PDS.     

Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex

Weak transcranial direct current stimulation (tDCS) of the human motor cortex results in excitability shifts which occur during and after stimulation. These excitability shifts are polarity-specific with anodal tDCS enhancing excitability, and cathodal reducing it. To explore the origin of this excitability modulation in more detail, we measured the input–output curve and motor thresholds as global parameters of cortico-spinal excitability, and determined intracortical inhibition and facilitation, as well as facilitatory indirect wave (I-wave) interactions. Measurements were performed during short-term tDCS, which elicits no after-effects, and during other tDCS protocols which do elicit short- and long-lasting after-effects. Resting and active motor thresholds remained stable during and after tDCS. The slope of the input–output curve was increased by anodal tDCS and decreased by cathodal tDCS. Anodal tDCS of the primary motor cortex reduced intracortical inhibition and enhanced facilitation after tDCS but not during tDCS. Cathodal tDCS reduced facilitation during, and additionally increased inhibition after its administration. During tDCS, I-wave facilitation was not influenced but, for the after-effects, anodal tDCS increased I-wave facilitation, while cathodal tDCS had only minor effects. These results suggest that the effect of tDCS on cortico-spinal excitability during a short period of stimulation (which does not induce after-effects) primarily depends on subthreshold resting membrane potential changes, which are able to modulate the input-output curve, but not motor thresholds. In contrast, the after-effects of tDCS are due to shifts in intracortical inhibition and facilitation, and at least partly also to facilitatory I-wave interaction, which is controlled by synaptic activity.     

Effect of contraction on lymphatic,venous, and tissue electrolytes and metabolites in rabbit skeletal muscle

Summary The effect of muscle contraction on lymphatic and plasma [K⁺], [Na⁺], [Ca²⁺], [Mg²⁺], [Cl^–], [P_i], [lactate] ([Lac^–]); [creatine] ([Cr]), ideal osmolality (OSM), and [protein] was evaluated in femoral venous blood and lymph specimens sampled from the calf muscles of rabbits before, in the course of, and after contractions. In addition, total [K⁺], [Na⁺], [Ca²⁺], [Mg²⁺], [Cl^–], and [H₂O] were analyzed in the muscle tissue. To facilitate lymph sampling both hind limbs were passively flexed and extended, in imitation of natural running movements, by an electrically driven crank. The muscles of one side also performed superimposed rhythmic isotonic contractions. Before contractions, lymphatic [K⁺], [Na⁺], [Ca²⁺], [Mg²⁺], [Lac^–], [Cr], and OSM did not significantly differ from corresponding femoral venous concentrations, [Cl^–], and [P_i] were significantly higher, [protein] significantly lower in the lymph than in the plasma. During contractions lymphatic [K⁺], OSM, [Lac^–], and [P_i] were raised significantly more in the lymph compared with the plasma concentrations. [Na⁺], [Cl^–], [Ca²⁺], and [Mg²⁺] showed only small changes in the course of contractions and thereafter, and they were altered in a similar way in the lymph and plasma. It was suggested that lymphatic and interstitial concentrations were in equilibrium. Comparing inactive with active muscles, the latter lost K⁺ but gained Na⁺, Cl^–, and H₂O, whereas minimal changes occurred in the [Ca²⁺] and [Mg²⁺]. The changes were discussed in connection with the hypothesis that electrolyte shifts might be involved in the activation of the muscular non-proprioceptive interstitial nerve endings which appear to play a role in reflexogenic cardiovascular and respiratory control.A preliminary report of this work has been given elsewhere [33]Supported by Deutsche Forschungsgemeinschaft     

Riluzole does not have an acute effect on motor thresholds and the intracortical excitability in amyotrophic lateral sclerosis

Intracortical excitability in amyotrophic lateral sclerosis (ALS) is impaired. The effectiveness of the glutamate antagonist riluzole (Rilutek, Rh?ne-Poulenc Rorer) in ALS has been shown in clinical studies. In healthy subjects it modifies intracortical excitability in a frequently used double-stimulus paradigm of transcranial magnetic stimulation (TMS). Under riluzole intracortical inhibition is enhanced in healthy individuals, although not always significantly, whereas intracortical facilitation has been described as reduced [10, 11]. We wanted to find out whether riluzole affects and potentially rebalances impaired intracortical excitability in ALS. We, therefore, enrolled 13 patients with clinically and electromyographically confirmed ALS into this study. Five patients had to be excluded because motor thresholds were too high to get reliable motor evoked potentials (MEPs). In the remaining 8 patients, mean age was 59.9 +/- 11.9 years (+/- standard deviation) and mean symptom duration 9.6 +/- 2.5 months. Intracortical excitability was assessed before and 1.5 hours after the first intake of a loading dose of 100 mg of riluzole using a conventional paired-pulse TMS paradigm with interstimulus intervals (ISI) ranging from 1-30 ms and intensities adjusted to yield MEPs of 1.0 mV for test pulses and of 90% active motor threshold for conditioning pulses. Patients' baseline results were compared to those of 9 age-matched, healthy control subjects. Before drug intake, motor thresholds did not differ between groups, but there was significantly less intracortical inhibition in the ALS patient group. Riluzole intake did not significantly alter motor thresholds or intracortical excitability in the ALS patients. We conclude that riluzole does not immediately influence intracortical excitability in ALS. Our results are in contrast to the findings of Stefan et al (1998) [14] where a partial normalization of intracortical inhibition in ALS was observed after at least 5 days of drug intake. The difference between that study and our result may indicate a delayed onset of riluzole's influence on intracortical excitability.     

Using Cost-Effectiveness Analysis to Address Health Equity Concerns

This articles serves as a guide to using cost-effectiveness analysis (CEA) to address health equity concerns. We first introduce the "equity impact plane," a tool for considering trade-offs between improving total health—the objective underpinning conventional CEA—and equity objectives, such as reducing social inequality in health or prioritizing the severely ill. Improving total health may clash with reducing social inequality in health, for example, when effective delivery of services to disadvantaged communities requires additional costs. Who gains and who loses from a cost-increasing health program depends on differences among people in terms of health risks, uptake, quality, adherence, capacity to benefit, and—crucially—who bears the opportunity costs of diverting scarce resources from other uses. We describe two main ways of using CEA to address health equity concerns: 1) equity impact analysis, which quantifies the distribution of costs and effects by equity-relevant variables, such as socioeconomic status, location, ethnicity, sex, and severity of illness; and 2) equity trade-off analysis, which quantifies trade-offs between improving total health and other equity objectives. One way to analyze equity trade-offs is to count the cost of fairer but less cost-effective options in terms of health forgone. Another method is to explore how much concern for equity is required to choose fairer but less cost-effective options using equity weights or parameters. We hope this article will help the health technology assessment community navigate the practical options now available for conducting equity-informative CEA that gives policymakers a better understanding of equity impacts and trade-offs.     

Changes in plaque fluoride levels by school-based fluoride rinsing and tablet programs in Bangladesh

The aim of this study was to evaluate the effects of school-based fluoride rinsing and tablet programs on plaque fluoride levels. A total of 42 children (8-9 years) were selected from two neighboring schools in Dhaka, Bangladesh. After caries recordings, vestibular plaque samples from the maxillary central incisors and mandibular first molars were collected and frozen on day 0 (baseline). The subjects of one school (rinsing group, n = 15) rinsed with 0.05% NaF, while those from the other school (tablet group, n = 16) used a 0.5 mg F tablet on the 5 school days during a 3-week period. The surfaces were sampled on the first and last school day every week. The fluoride and protein contents of each sample were analyzed using micro-techniques. The median plaque fluoride levels were 9.1 ppm at baseline in the rinsing group and 2.5 ppm in the tablet group (P < 0.05). This difference could in part be related to reported fluoride toothpaste usage. After 4 days on the fluoride programs, plaque fluoride levels in the rinsing group increased to 27.3, 24.5 and 14.2 ppm in the 3 consecutive weeks. The corresponding values after tablet usage were 8.0, 6.5 and 7.1 ppm, respectively. After 3 days without fluoride during the weekends, levels declined towards baseline values in both groups. Hence, the plaque fluoride levels in 8 to 9-year-old Bangladeshi children were increased by both rinsing and tablet programs, but the effect was not detectable 3 days later.     

Sentinel Node Biopsy in Melanoma of the Trunk and the Extremities in Tumescent Local Anesthesia

Background.  The sentinel node biopsy (SNB) of axilla and groin is a common staging procedure and can be done in both general anesthesia and local anesthesia.
Objective.  To investigate the efficacy of tumescent local anesthesia (TLA) as a widely used type of local anesthesia in dermatologic surgery for the SNB of axilla and groin.
Method.  From 1999 to 2002, 195 patients underwent a SNB of axilla or groin. A 0.1% tumescent solution with prilocaine was used. In cases in which local anesthesia did not produce complete analgesia, there was additional medication using Midazolam and Tramadol.
Results.  In 74.9% of the patients, TLA was sufficient as the sole method. In 25.1%, sedation became necessary. Additional medication was required for 31.9% of the patients with SNB in the axilla and for 17.3% with SNB in the groin; 26.6% of the patients with SNB of both axillas and 25% with SNB of the axilla and the groin received additional medication using Midazolam. Two patients with a SNB of the axilla received a combination of Midazolam and Tramadol.
Conclusion.  SNB of the axilla and the groin in TLA is a good alternative to other anesthetic techniques, for example, general anesthesia or infiltration anesthesia.     

Availability, distribution and use of emergency obstetric care in northern Tanzania

The objective of this study is to determine the availability, distribution and quality of facilities providing delivery services, as well as their use by pregnant women. The study is a survey of all facilities providing delivery services (n = 129) in six districts in northern Tanzania. The framework provided by the UNICEF/UNFPA/WHO (UN) Guidelines is applied. An attempt is made to answer the first three questions in this audit outline: are there enough emergency obstetric care (EmOC) facilities? Are they well distributed? And are enough women using them? The results show that there is a very low availability of basic emergency obstetric care (BEmOC) units (1.6/500,000), and a relatively high availability of comprehensive emergency obstetric care (CEmOC) units (4.6/500,000), both with large urban/rural variation. The percentage of expected deliveries in EmOC facilities is 36%, compared with the UN Guidelines minimum accepted threshold of 15%. Nevertheless, the distribution shows a much higher utilization in urban districts compared with rural, indicating that mothers have to travel long distances to receive adequate services when in need of them. The paper also discusses the provisional context of the services in terms of level of facilities providing them and their public/private mix. Most facility deliveries are conducted at CEmOC facilities. Pregnant women tend to utilize the services of voluntary agencies to a greater degree than government services in rural areas, while the government services have a higher burden of the workload in urban areas. A majority (86%) of the deliveries occurring in voluntary agency facilities occur in a qualified EmOC facility. Against a backdrop of a large availability of any facility regardless of their emergency obstetric care status (41.9/500,000), this paper argues that given the large number of potential BEmOC facilities, it seems more efficient to shift resources within the BEmOC level, compared with from CEmOC level down to BEmOC level, to improve access to quality services. There is a large potential for quality improvement, in particular at dispensary and health centre levels. We argue that the main barrier to access to quality care is not the mother's ignorance or their ability to get to a facility, but the actual quality of care meeting them at the facility.     

Heparin-mediated extracorporeal LDL precipitation treating a peripheral arterial disease patient suffering from repeated postoperative bypass occlusion

Acute occlusion of a peripheral artery is a serious complication in peripheral arterial disease (PAD). Traditionally open surgical intervention in combination with antithrombotic therapy is the choice for treatment but the beneficial effects of both strategies are limited often by the patient's situation and therapeutic side effects. Heparin-mediated extracorporeal low-density lipoprotein precipitation (H.E.L.P.) apheresis efficiently removes circulating atherogenic lipoproteins, fibrinogen and C-reactive proteins as well as various proinflammatory and procoagulatory factors. We first report H.E.L.P. apheresis treating a PAD patient suffering from repeated postoperative femoropopliteal bypass graft occlusion, first, intensively, followed by weekly intervals. Limb amputation was avoided and the patient is doing well now. Angiography revealed bypass graft remained patent half a year after operation. This case report might help to design the regime for preventing postoperative bypass occlusion in patients with hyperlipidemia or hyperfibrinogenemia.