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.     

Public health workforce information: a state-level study.

A two-stage sample survey was used to estimate the size of Texas' professional public health workforce and to describe its composition in terms of employment settings, job characteristics, and individual characteristics. The estimated 17,700 public health professionals employed in 1995 represented approximately three percent of the state's total health workforce. About 55 percent of all these professionals worked in agencies that provide population-based public health services. An estimated seven percent had formal public health education. These findings raise issues concerning the numerical adequacy of the state's supply of public health professionals, the adequacy of their educational preparation, and the human resources capacity of the state's official public health agencies.     

Comparison of intraocular pressure lowering by topical and systemic carbonic anhydrase inhibitors in the rabbit.

We compared the effect on intraocular pressure (IOP) of maximal doses of a topical carbonic anhydrase inhibitor (CAI) at acidic and alkaline pH where it is maximally effective with full systemic CA inhibition in ocular normotensive New Zealand Albino rabbits. Tonometric IOP levels were measured hourly during 3 hour control period. Topical MK-417 (pKa 5.8, 8.3), a close congener of MK-507 (Dorzolamide) was given as a 1.4% solution at pH 4.5 (n=6) and pH 9.2 (n=6). MK-417 was instilled to the left eye with the right eye used as an untreated control. One hour later methazolamide was given intravenously at 10 mg/kg, a dose known to give full inhibition of the enzyme. Control IOP (mm Hg) was 19.12+/-0.50. One hour following MK-417, the left eye IOP was 13.40 +/-0.70 (pH 4.5) and 13.25+/-0.70 (pH 9.2). The right eye pressure was unchanged. Methazolamide injection at this time gave no further drop in the left eye IOP at either pH. IOP in the right eye fell to 14.00+/-0.70 so that 2 hours after methazolamide injection, the 2 eyes had the same pressure. In conclusion, topical CAI in sufficient dose and correct pH yields IOP lowering equivalent to a maximally effective dose of systemic CAI in rabbits.     

Laparoscopic splenectomy in children with hematological disorders: preliminary experience at the Children's Hospital of New Orleans

Minimally invasive surgery has recently gained acceptance as the surgical approach of choice for a variety of surgical disorders in children. Although traditional open surgery is still regarded as the standard approach for a splenectomy in children when necessary for hematologic disorders a few cases of successful laparoscopic splenectomy (LS) have been reported. We present our initial 11 cases of LS in children assessing surgical outcome. Eleven patients ages 2 through 15 years underwent LS between June of 1996 and July of 1999 at the Children's Hospital of New Orleans. Indications for surgery included idiopathic thrombocytopenic purpura, congenital spherocytosis, and hemolytic anemia. In all patients the diameter of the spleen was less than 15 cm. Surgical outcome was assessed according to the following parameters: operative time, postoperative length of stay, postoperative morbidity, and cosmetic results. Data were accumulated on the basis of retrospective chart review. LS was completed in all 11 patients. Postoperative morbidity was minimal and the median postoperative stay was 2.4 days (range 1-5). Mean operative time was 3 hours and 10 minutes (range 1.5-7 hours) with the last six procedures completed in an average of just over 2 hours. Intravenous analgesia was discontinued in <48 hours in all patients. Cosmetic results were judged excellent in all cases. We conclude that LS was safe in children with certain hematologic disorders. Adequate selection of patients, appropriate preoperative preparation of patients, meticulous surgical technique, and careful postoperative care were key factors in obtaining the same long-term results as with open surgery.     

Laparoscopic fundoplication in children with previous abdominal surgery

BACKGROUND/PURPOSE: In our institution, many children requiring antireflux surgery for gastroesophageal reflux have had previous abdominal surgery, usually gastrostomy tube or ventriculoperitoneal (VP) shunt placement. The authors review their laparoscopic Nissen fundoplication (LNF) experience in children with previous abdominal surgery assessing surgical outcome. METHODS: A total of 82 consecutive LNFs performed at our institution between January 1996 and September 1998 were reviewed. Follow-up ranged from 1 month to 32 months (average, 8.9 months). LNF was performed without dividing short gastric vessels (Rosetti modification) through a standard 5-port technique. RESULTS: A total of 26 of 82 patients (31.7%) had previous abdominal surgery and were divided into 2 groups: gastrostomy (n = 17) and VP shunt (n = 11) with 2 crossovers. A total of 14 of 17 (82.3%) in the gastrostomy group had percutaneous endoscopic gastrostomy (PEG) placement versus 3 of 17 (17.6%) by open technique (open). Four patients in the VP group had multiple surgeries (range, 1 to 10, average, 2.3). LNF was completed in 25 of 26 (96.2%). One operation was converted to an open procedure because of severe adhesions. In 13 of 17 (76.5%) the previous gastrostomy was not taken down. In 4 of 17 (23.5%), the gastrostomy was taken down to complete the procedure: 2 of 3 (66.7%) of the open group versus 2 of 14 (14.3%) of the PEG group. All 11 (100%) of the VP group had successful LNF. Two of 11 (18.2%) had shunt dysfunction at 2 months (shunt infection) and 4 months (clogged distal shunt), respectively. There have been no cases of recurrent reflux, and all gastrostomies and VP shunts were functional at the time of this report. CONCLUSIONS: Previous abdominal surgery is common in children with gastroesophageal reflux disease requiring an antireflux procedure. The authors conclude from these preliminary results that laparoscopic Nissen fundoplication can be performed safely with minimal morbidity and excellent functional results in children with gastrostomies or ventriculoperitoneal shunts.     

The role of contextual versus discrete drug-associated cues in promoting the induction of psychomotor sensitization to intravenous amphetamine

The environmental context in which psychostimulant drugs are administered can have a large effect on both their acute psychomotor activating effects and their ability to induce the psychomotor sensitization associated with repeated drug administration. For example, the acute effects of amphetamine and the development of psychomotor sensitization to amphetamine and cocaine are enhanced when they are administered in a distinct and relatively novel test environment, relative to when they are given in the home cage, in the absence of any environmental stimuli predictive of drug administration. The experiments reported here were designed to further examine this phenomenon and to test the hypothesis that the ability of a distinct context to promote robust psychomotor sensitization is due to its ability to reliably signal (cue) drug administration. Specifically, we compared the ability of contextual cues (a distinct test environment) and discrete cues (light, tone and/or odor), which both reliably predict drug administration, to promote the induction of sensitization. The psychomotor stimulant effects (rotational behavior) of repeated intravenous infusions of 0. 5 mg/kg amphetamine were assessed in rats for whom drug treatments were signaled either: (1) by placement into a distinct test environment; (2) by presentation of discrete cues; or (3) rats for whom drug treatments were given in the home environment in the absence of any environmental cues. Amphetamine produced robust sensitization when given in association with placement into a distinct test environment. The same treatment failed to produce sensitization when the drug was given unsignaled in the animal's home cage. Most importantly, signaling drug administration by presenting discrete cues was not sufficient to promote the robust sensitization seen when treatments were given in a distinct test environment. These results confirm that the induction of psychomotor sensitization can be powerfully modulated by environmental context and further establish that, although contextual stimuli associated with a distinct test environment promote robust sensitization, discrete cues that merely predict drug administration do not have this property. Possible reasons for the difference in the ability of contextual versus discrete environmental cues to promote sensitization are discussed.     

Structure of the processive rubber oxygenase RoxA from Xanthomonas sp

Rubber oxygenase A (RoxA) is one of only two known enzymes able to catalyze the oxidative cleavage of latex for biodegradation. RoxA acts as a processive dioxygenase to yield the predominant product 12-oxo-4,8-dimethyl-trideca-4,8-diene-1-al (ODTD), a tri-isoprene unit. Here we present a structural analysis of RoxA from Xanthomonas sp. strain 35Y at a resolution of 1.8 Å. The enzyme is a 75-kDa diheme c-type cytochrome with an unusually low degree of secondary structure. Analysis of the heme group arrangement and peptide chain topology of RoxA confirmed a distant kinship with diheme peroxidases of the CcpA family, but the proteins are functionally distinct, and the extracellular RoxA has evolved to have twice the molecular mass by successively accumulating extensions of peripheral loops. RoxA incorporates both oxygen atoms of its cosubstrate dioxygen into the rubber cleavage product ODTD, and we show that RoxA is isolated with O₂ stably bound to the active site heme iron. Activation and cleavage of O₂ require binding of polyisoprene, and thus the substrate needs to use hydrophobic access channels to reach the deeply buried active site of RoxA. The location and nature of these channels support a processive mechanism of latex cleavage.     

Ankyrin-B structurally defines terminal microdomains of peripheral somatosensory axons

Axons are subdivided into functionally organized microdomains, which are required for generation and propagation of action potentials (APs). In the central nervous system (CNS), APs are generated near the soma in the axon initial segment (AIS) and propagated by nodes of Ranvier (noR). The crucial role of the membrane adapter proteins ankyrin-B and ankyrin-G as organizers of AIS and noR is now well established. By comparison, little is known on the localization and function of these proteins in sensory axon terminals of the peripheral nervous systems (PNS). Here, we tested the hypothesis that somatosensory PNS terminals are organized by distinct members of the ankyrin protein family. We discovered a specific distribution of ankyrin-B in somatosensory axon terminals of skin and muscle. Specifically, ankyrin-B was localized along the membrane of axons innervating Meissner corpuscles, Pacinian corpuscles and hair follicle receptors. Likewise, proprioceptive terminals of muscle spindles exhibited prominent ankyrin-B expression. Furthermore, ankyrin-B expression extended into nociceptive and thermoceptive intraepidermal nerve fibers. Interestingly, all studied somatosensory terminals were largely devoid of ankyrin-G, indicating that this scaffolding protein does not contribute to organization of mechanoelectric transduction zones in peripheral somatosensory neurons. Instead, we propose that ankyrin-B serves as a major membrane organizer in mechanoreceptive and nociceptive terminals of the PNS.