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This study aimed to determine if conventional extra-anatomic bypass and graft removal versus aggressive attempts at graft preservation have better survival and limb salvage in patients with localized groin wound infections of vascular grafts.

One strategy to address the impending shortage of vascular surgeons is to augment interest in the trainee pipeline. Endovascular procedures are unique to vascular surgery (VS) and endovascular simulations have proven effective at generating VS interest in the past. Like endovascular techniques, the use of ultrasound (US) testing in VS is unique among medical specialties. We hypothesized that an interactive US demonstration would increase VS interest in preclinical medical students.

As antimicrobial resistance threatens our ability to treat common bacterial infections, new antibiotics with limited cross-resistance are urgently needed. In this regard, natural products that target the bacterial ribosome have the potential to be developed into potent drugs through structure-guided design, provided their mechanisms of action are well understood. Here we use inverse toeprinting coupled to next-generation sequencing to show that the aromatic polyketide tetracenomycin X primarily inhibits peptide bond formation between an incoming aminoacyl-tRNA and a terminal Gln-Lys (QK) motif in the nascent polypeptide. Using cryogenic electron microscopy, we reveal that translation inhibition at QK motifs occurs via an unusual mechanism involving sequestration of the 3′ adenosine of peptidyl-tRNALysin the drug-occupied nascent polypeptide exit tunnel of the ribosome. Our study provides mechanistic insights into the mode of action of tetracenomycin X on the bacterial ribosome and suggests a path forward for the development of novel aromatic polyketide antibiotics.

AbstractInfants with complex cyanotic CHD can become symptomatic from insufficient pulmonary blood supply following either ductal closure or due to outflow tract obstruction. Blalock–Taussig shunt mortality remains significant and recent studies have highlighted the advantages of using transcatheter alternatives. We present here our experience in changing our primary choice of palliation from the Blalock–Taussig shunt to transcatheter palliation with either a ductal stent or, if antegrade flow is present, a right ventricular outflow tract stent.This is a retrospective, single-unit cohort study. Eighty-seven infants underwent palliation for insufficient pulmonary blood flow at under 3 months of age between 2012 and 2019. On an intention-to-treat basis, 29 underwent insertion of a Blalock–Taussig shunt, 36 duct stents, and 22 right ventricular outflow tract stents at median ages of 15, 9, and 32 days, respectively, and median weights of 3.3, 3.1, and 3.1 kg, respectively. No primary Blalock–Taussig shunts have been performed in our institution since 2017.At 30-days there had been one death in each group (univariable p = 0.93) and deaths prior to repair totalled three in the shunt group, four in the ductal stent group, and two in the right ventricular outflow tract stent group (univariable p = 0.93). Reintervention on the pulmonary circuit prior to next stage of surgery was more frequent in those undergoing transcatheter intervention, reaching statistical significance by logrank (p = 0.012).In conclusion, within this work we provide further evidence of the safety and efficacy of transition from a primary surgical to primary transcatheter palliation pathway in infants with insufficient pulmonary blood supply.

The most widely reported threat to boreal and mountain populations of woodland caribou (Rangifer tarandus caribou; caribou) involves habitat‐ or disturbance‐mediated apparent competition (DMAC). With DMAC, natural and anthropogenic disturbances that increase the abundance of deciduous‐browsing cervids (e.g., moose [Alces alces], deer [Odocoileusspp.]) are thought to promote predator (especially wolf [Canis lupus]) numbers, which heightens predation risk to caribou. We know most about the effects of DMAC on caribou where the species is under threat by anthropogenic activities in relatively productive southern boreal and mountain systems. Yet, >60% of extant boreal caribou range in North America consists of northern shield and taiga ecoregions of low productivity where caribou may compete with only 1 ungulate species (moose) in the context of DMAC. In this environment, we know very little of how DMAC acts as a limiting factor to caribou. In Saskatchewan, Canada, from 2014–2018, using a combination of vegetation sampling, aerial surveys, and telemetry data (n= 38 wolves), we searched for evidence of DMAC (trends in data consistent with the hypothesis) in an 87,193‐km2section of the Western Boreal Shield, a poorly productive but pristine region (0.18% of land cover classed as an anthropogenic feature) with a historically high fire‐return interval (47% of stands aged <40 years). Despite the high levels of disturbance, moose density was relatively low (47 moose/1,000 km2), likely because of the scarcity of deciduous or mixed‐wood stands and low abundance of deciduous browse in the young conifer stands that dominated the landscape. In contrast, boreal caribou density was relatively high for the species (37 caribou/1,000 km2). Wolf density (3.1 wolves/1,000 km2) and pack sizes (x¯= 4.0 wolves/pack) were low and resident (established) territories were large (x¯= 4,360 km2; 100% minimum convex polygon). The low density of wolves mirrored the low (standardized) ungulate biomass index (UBI; moose + boreal caribou) of the study area (0.36 UBI/km2). We conclude that wolf and hence caribou populations were not responding in accordance with the outcomes generally predicted by DMAC in our study area because the requisite strong, positive response to fire of deciduous‐browse and alternate‐prey abundance was lacking. As a limiting factor to caribou, DMAC is likely modulated at a macroecological scale by factors such as net primary productivity, a corollary to the general hypothesis that we advance here (i.e., primary productivity hypothesis of DMAC). We caution against managing for caribou based on the presumption of DMAC where the mechanism does not apply, which may include much of boreal caribou range in the north. © 2020 The Wildlife Society. At present, our management approach to boreal caribou throughout their Canada‐wide range is predicated on the assumption that disturbance‐mediated apparent competition is an important consideration for all boreal caribou populations. The supposition that large‐scale wildfire disturbance, resulting in younger forests, can generate the habitat conditions necessary to affect increased abundance of alternate prey, in turn increasing wolf populations and limiting caribou population growth, is inconsistent with what we observed in the Saskatchewan Boreal Shield. Instead, we observed low densities of wolves and low densities of moose despite high natural disturbance in our study area.

Knee osteoarthritis (OA) is a heterogeneous disease associated with substantial effects on quality of life, and its clinical management is difficult. Among the several available guidelines for the management of knee OA, those from OARSI and ESCEO were updated in 2019. Here, we examine the similarities and differences between these two guidelines and provide a narrative to help guide health-care providers through the complexities of non-surgical management of knee OA. OARSI and ESCEO both recommend education, structured exercise and weight loss as core treatments, topical NSAIDs as first-line treatments and oral NSAIDs and intra-articular injections for persistent pain. Low-dose, short-term acetaminophen, pharmaceutical grade glucosamine and chondroitin sulfate are recommended by ESCEO whereas OARSI strongly recommends against their use (including all glucosamine and chondroitin formulations). Despite this difference, the two guidelines are consistent in the majority of their recommendations and provide useful treatment recommendations for individuals with OA and health-care providers.

To assess the association between occupational exposures and knee osteoarthritis (OA). We systematically searched for observational studies that examined the relationship between occupational exposures and knee OA and total knee replacement. Four databases were searched up to October 1, 2019. Two reviewers independently assessed study quality using the Newcastle‐Ottawa Scale and evidence quality using the Grading of Recommendations Assessment, Development and Evaluation approach. Subgroup meta‐analyses were conducted for important study characteristics and each type of occupational exposure. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for the meta‐analysis using random‐effects models. Eighty eligible studies were identified including 25 case–control (n = 20,505 total participants), 36 cross‐sectional (n = 139,463 total participants), and 19 cohort studies (n = 16,824,492 total participants). A synthesis of 71 studies suggested increased odds of knee OA (OR 1.52 [95% CI 1.37–1.69]) by combining different physically demanding jobs and occupational activities as compared to sedentary occupations and/or low‐exposure groups. Odds of knee OA were greater in males and in industry‐based studies and studies assessing lifetime occupational exposures. There were 9 specific job titles that were associated with knee OA, including farmer, builder, metal worker, and floor layer. Occupational lifting, kneeling, climbing, squatting, and standing were all associated with higher odds of knee OA as compared to the odds of knee OA in sedentary workers. Strenuous, physically demanding occupations and occupational activities were associated with increased odds of knee OA as supported by moderate‐quality evidence. Specifically, agricultural and construction sectors, which typically involve heavy lifting, frequent climbing, prolonged kneeling, squatting, and standing, carried increased odds of knee OA.

Pulsed electromagnetic field (PEMF) therapy is a potentially useful treatment for osteoarthritis (OA), but its effectiveness is still controversial. This study aimed to examine the effects of PEMF therapy and PEMF parameters on symptoms and quality of life (QOL) in patients with OA.

Nature uses multivalency to govern many biological processes. The development of macromolecular and cellular therapies has largely been dependent on engineering similar polyvalent interactions to enable effective targeting. Such therapeutics typically utilize high-affinity binding domains that have the propensity to recognize both antigen-overexpressing tumors and normal-expressing tissues, leading to “on-target, off-tumor” toxicities. One strategy to improve these agents’ selectivity is to reduce the binding affinity, such that biologically relevant interactions between the therapeutic and target cell will only exist under conditions of high avidity. Preclinical studies have validated this principle of avidity optimization in the context of chimeric antigen receptor (CAR) T cells; however, a rigorous analysis of this approach in the context of soluble multivalent targeting scaffolds has yet to be undertaken. Using a modular protein nanoring capable of displaying ≤8 fibronectin domains with engineered specificity for a model antigen, epithelial cell adhesion molecule (EpCAM), this study demonstrates that binding affinity and ligand valency can be optimized to afford discrimination between EpCAMHigh(2.8–3.8 × 106antigens/cell) and EpCAMLow(5.2 × 104to 2.2 × 105antigens/cell) tissues both in vitro and in vivo.

Developing robust manufacturing processes for electric traction motors is essential to support GM's electrification roadmap. When assembling an electric motor, many copper components in the form of wires, bars, and bus rings are joined together. The joints must be highly conductive to achieve high efficiency as well as mechanically strong to survive the harsh service environment. A potential joining method that could meet the above-mentioned requirements is tungsten inert gas arc welding (TIG). TIG welding offers the highest energy density compared with other arc welding processes and requires far less capital investment compared with laser and electron beam welding. In this report, we will four factors critical to the welding process, namely: the type of shielding gas, weld current, electrode to workpiece distance, and weld time; and how each factor influences the weld quality.

In this narrative review article, we critically assess the current state of the osteoarthritis (OA) drug development pipeline. We discuss the current state-of-the-art in relation to the development and evaluation of candidate disease-modifying OA drugs (DMOADs) and the limitations associated with the tools and methodologies that are used to assess outcomes in OA clinical trials. We focus on the definition of DMOADs, highlight the need for an updated definition in the form of a consensus statement from all the major stakeholders, including academia, industry, regulatory agencies, and patient organizations, and provide a summary of the results of recent clinical trials of novel DMOAD candidates. We propose that DMOADs should be more appropriately targeted and investigated according to the emerging clinical phenotypes and molecular endotypes of OA. Based on the findings from recent clinical trials, we propose key topics and directions for the development of future DMOADs.

Dan installed retractable landing lights in the wings and a taxi light on the nose gear. A lighting kit from Dave's Electronics includes navigation as well as anti-collision strobes. DEPARTMENTS EMAIL ENTRIES TO: MAN@AIRAGE.COM CESSNA 310 Dan Irwin, Champaign, Ilinois This fantastic looking Cessna 310 was Dan's 14-month winter project. [Extracted from the article]

Cryoneurolysis, cold-induced reversible conduction block of peripheral nerves, is an effective treatment for reducing knee osteoarthritis (OA) symptoms and opioid use following knee arthroplasty. There are however, limited data concerning its use for ankle OA. Our aim was to assess clinically significant long-term symptomatic relief of ankle OA with cryoneurolysis.

Bark beetle-induced mortality in forested landscapes of structurally uniform, even-aged lodgepole pine stands has inspired a growing interest in the potential of silvicultural treatments to enhance resilience by increasing spatial and vertical complexity. Silvicultural treatments can simulate mixed-severity disturbances that create multiaged lodgepole pine stands, which, along with heterogeneous forest landscapes, can play a role in mitigating susceptibility to primary disturbance agents (bark beetles and wildfire). With this article, we review multiaged lodgepole pine stand dynamics and discuss variable-retention harvesting as a silvicultural option for lodgepole pine. We describe the establishment and initial outcomes of an experimental variable-retention harvesting project established at the Tenderfoot Creek Experimental Forest (Montana) in 1999–2003 and the objectives of a collaborative multiagency effort that is presently revisiting and analyzing that experiment.

The automotive industry is developing designs and manufacturing processes for a new generation of electric motors intended for use in hybrid and electric vehicles. This paper is focused on using solid-state welding to join rectangular wires in the fabrication of motor stators. Resistance welding has not typically been applied to copper due to its very high electrical conductivity; however through optimization of the current and pressure profiles, excellent quality copper-to-copper joints have been demonstrated with a technique known as resistance mash welding. A better understanding of resistance mash welding characteristics will help advancements in its application for stators. The limitations of this application will be discussed.

The article offers instructions for creating a pitcher using the Nerikomi technique of slab-building with inlaid clays.

The article discusses the First Minnesota Volunteer Infantry during the U.S. Civil War. According to the article, the infantry was one of the few units in the Union army to have published an infantry newspaper during the war. The article states that the First Minnesota included many printers and editors. The article examines their service during the war including fighting at Bull Run in 1861, rebuilding a bridge at Harpers Ferry, West Virginia, and occupying land near Winchester, Virginia. The article also describes how some of the regiment's printers overtook the offices of the Berryville, Virginia, newspaper the "Conservator," in 1862 to print an edition of "The First Minnesota" newspaper. The article discusses printers in the regiment including Edward A. Stevens and Frank J. Mead.

To examine whether foot and/or ankle pain increases the risk of knee OA.

A 53-year-old right-handed man was scheduled to receive 6 treatments of electroconvulsive therapy (ECT) for intractable depression. He was being treated for long-standing hypertension with nadolol and had no history of cardiopulmonary disease. Six months previously, he received 6 nondominant, unilateral ECT treatments. During each of these treatments, his blood pressure increased transiently to as high as 250/150, but he experienced no adverse consequence. He commenced the current course of ECT with well-controlled blood pressure (145/90). During his first bilateral treatment, his blood pressure rose to 280/160, and pulmonary edema ensued. Clinically evident pulmonary edema after ECT is an uncommon event that rarely has been described in the literature.

X-ray Absorption Near Edge Structure (XANES) has been used to characterize the chemistry of tribochemical wear pads generated from a paraffinic base oil with a zinc-dialkyl-dithiophosphate additive on steel surfaces and high-velocity oxygen fuel (HVOF) thermal spray coatings. The phosphorus K- and L- edge XANES spectra show that the tribofilms formed on steel and the HVOF coatings have the same chemical nature. Also, mechanical properties of these tribofilms were examined by nanoindentation techniques using both Hysitron and Interfacial Force Microscopy (IFM) instruments. The elastic moduli extracted from indentation force-displacement (f-d) curves have demonstrated that tribofilms on steel and HVOF coatings have similar surface topography and mechanical properties.

Recent reports suggest that amyotrophic lateral sclerosis (ALS) is caused by one or more unidentified neurotoxins that are poorly metabolized in patients to less toxic and more readily excreted compounds, and that a genetically determined defect in cysteine degradation and in inorganic sulfate production is the mechanism underlying a failure to metabolize xenobiotics normally in ALS. We measured concentrations of total cysteine and of inorganic sulfate in the plasma of age-matched groups of ALS patients and healthy control subjects and found no differences. l-Cysteine, a putative endogenous neurotoxin in ALS, was present in equal concentrations in autopsied brain from ALS patients and controls.

Amino acid contents were measured in autopsied brains of eight patients with the sporadic form of amyotrophic lateral sclerosis (ALS) and in brains of control subjects dying without neurologic or psychiatric disease. Glutamic acid content was reduced in most brain regions and in the cervical cord in the ALS patients, while glutamine contents were normal. Taurine contents were increased, and γ-aminobutyric acid contents were decreased in some brain regions in the ALS patients. The brain glutamate deficiency in ALS is unexplained, but insufficient production or release of this excitatory neurotransmitter might have important secondary effects on motor neurons.

We present the first pathologic descriptions of the puppet-like syndrome of Angelman based on autopsy studies of a 21-year-old woman. The noteworthy findings were a small brain with mild cerebral atrophy but normal gyral development. There was marked cerebellar atrophy with loss of Purkinje and granule cells and extensive Bergmann's gliosis. Study of dendrite morphology using Golgi impregnations of the visual cortex revealed a prominent decrease in dendritic arborization of layer 3 and layer 5 pyramidal neurons. Quantitative Golgi analysis also revealed a significant decrease in the numbers of dendritic spines in apical layer 3 dendrites and both apical and basal layer 5 dendrites. Neurochemical studies of frozen brain tissue demonstrated markedly reduced y-aminobutyric acid content in the cerebellar cortex, as well as elevated glutamate content in the frontal and occipital cortices. Although there are no definite morphologic correlates of many of the clinical signs, the pronounced dendritic pathology and neurochemical abnormalities in cerebral cortex may provide a physiologic basis for mental retardation.

We measured amino acid contents in the brains of 11 patients with dominantly inherited cerebellar disorders. Despite clinical similarities, three biochemically different disorders were found. One disorder, with demonstrated HLA linkage in one pedigree, was characterized by moderate reduction of aspartate and glutamate contents in cerebellar cortex alone. In a second disorder, aspartate and glutamate contents were reduced markedly in other brain areas as well as in cerebellar cortex. Aspartate and glutamate contents were normal in cerebellar cortex in the third disorder. GABA content in cerebellar cortex and dentate nucleus was reduced in some patients with each disorder, whereas cerebellar taurine content was normal in all patients. Aspartate deficiency in cerebellar cortex did not result from lack of aspartate aminotransferase or pyruvate carboxylase activity. These amino acid abnormalities probably imply loss of specific cerebellar neurons.

We measured levels of γ-aminobutyric acid (GABA) in the CSF and in the autopsied brain of patients with dialysis encephalopathy. GABA concentrations were low in the CSF of three of five living patients. Mean GABA content was reduced by 30 to 50 in five brain regions (frontal, occipital, and cerebellar cortex, caudate nucleus, and medial dorsal thalamus) in five fatal cases. GABA content was normal in brain regions where GABA is characteristically reduced in Huntington's disease. Choline acetyltransferase activity was diminished (by 25 to 35) in cerebral cortex of the dialysis encephalopathy patients.

Does the role of administra tors of smaller secondary schools really differ from that of their counterparts at larger schools? A series of surveys of smaller secondary school administrators reveals how their position has changed during the past four years and how they spend their time during the school day.

Summary: Glycine content and enzyme activity of the glycine cleavage system were compared in autopsied brain from five infants dying with glycine encephalopathy and four control infants, including two with other types of hyperglyeinemia. Glycine content was elevated 2- to 8-fold and glycine cleavage enzyme activity was undetectable in the brains of the glycine encephalopathy patients. Glycine content and enzyme activity were normal in the brains of the control patients, including one with ketotic hyperglyeinemia secondary to methylmalonic acidemia. Prolonged dialysis failed to restore glycine cleavage enzyme activity in brain homogenates of glycine encephalopathy patients, and these homogenates failed to inhibit enzyme activity when added to homogenates of control brain. Radioactive bicarbonate was converted to radioactive glycine by control brain, but not by glycine encephalopathy brain. This Finding, together with the results of recombination experiments between solubilized human brain enzymes and purified protein components of the bacterial glycine cleavage system of Arthrobacter globiformis, indicates that the enzyme defect in glycine encephalopathy involves at least the second or H protein of the 4-protein glycine cleavage enzyme system.Speculation: The severe neurologic syndrome that characterizes glycine encephalopathy, in contrast to some other forms of hyperglycinemia, is probably caused by absence of glycine cleavage enzyme activity and marked elevation of glycine content in infantile brain. Since symptoms of this inherited disorder only appear shortly after birth, a firmly bound endogenous inhibitor of the glycine cleavage enzyme may accumulate in brain of affected infants, who have been protected during fetal life by clearance of the putative inhibitor across the placenta.

Seven patients with Huntington disease were treated with aminooxyacetic acid (AOAA), an inhibitor of μgM-aminobutyric acid aminotransferase (GABA-T), in an effort to alleviate symptoms by increasing brain GABA content. AOAA was given orally in a placebo-controlled crossover trial in which patients, relatives, and three of the evaluating physicians remained blind. Toxic symptoms occurred in all seven patients when AOAA dosage was increased beyond 2 mg per kilogram per day, and included drowsiness, ataxia, seizures, and psychotic behavior. In five patients who took AOAA for 4 months, no clinical improvement was observed. Biochemical monitoring showed that less inhibition of hepatic GABA-T enzyme activity was achieved than in patients treated with large doses of isoniazid. Results of this trial neither support nor exclude the possible therapeutic usefulness of increasing brain GABA content in Huntington disease.

Glycine content and enzyme activity of the glycine cleavage system were compared in autopsied brain from five infants dying with glycine encephalopathy and four control infants, including two with other types of hyperglyeinemia. Glycine content was elevated 2− to 8-fold and glycine cleavage enzyme activity was undetectable in the brains of the glycine encephalopathy patients. Glycine content and enzyme activity were normal in the brains of the control patients, including one with ketotic hyperglyeinemia secondary to methylmalonic acidemia. Prolonged dialysis failed to restore glycine cleavage enzyme activity in brain homogenates of glycine encephalopathy patients, and these homogenates failed to inhibit enzyme activity when added to homogenates of control brain. Radioactive bicarbonate was converted to radioactive glycine by control brain, but not by glycine encephalopathy brain. This Finding, together with the results of recombination experiments between solubilized human brain enzymes and purified protein components of the bacterial glycine cleavage system of Arthrobacter globiformis, indicates that the enzyme defect in glycine encephalopathy involves at least the second or H protein of the 4-protein glycine cleavage enzyme system.

We have described two siblings who excrete massive amounts (up to 3.89 mmol/24 hr) of N-formiminoglutamic acid (FIGLU) in their urine. This unusual compound was isolated from urine, purified, and firmly identified as FIGLU by combined gas chromatography-mass spectrometry. The patients presumably have a deficiency in activity of the hepatic enzyme, glutamate formiminotransferase, which carries out the fourth sequential step in the main pathway of histidine degradation. Unlike children reported previously with this disorder, our patients had normal serum folate levels, had no hematologic abnormalities, and were not mentally retarded. Very small amounts of FIGLU were present in the plasma of one of the patients, but FIGLU was not detectable in the cerebrospinal fluid of either patient. Administration of pharmacologic doses of folic or folinic acid produced a decrease in excretion of FIGLU in urine. Histidine loading caused a small and comparable urinary excretion of FIGLU in the children's parents and in control adult subjects.

We describe biochemical abnormalities in autopsied brain of a patient with early Huntington's disease (HD) who died of pentobarbital overdosage while under treatment with isoniazid (INH). The brain contained hydrazine, a terminal metabolite of INH, which inhibits γ-aminobutyric acid (GABA) aminotransferase. GABA content in the basal ganglia was higher than expected for HD, and GABA content was supranorma1 in some brain regions. Homocarnosine (GABA-histidine) content was greatly elevated in all brain regions, suggesting chronic GABA elevation in life. Therefore, the increase in brain GABA content observed in experimental animals given INH or hydrazine also occurs in human patients.

We describe clinical and biochemical changes in seven patients with Huntington disease given isoniazid (INH) in dosages three to five times greater than normally used in tuberculosis. Because INH inhibits the enzyme y-aminobutyric acid aminotransferase (GABA-T), and increases GABA content in the brains of experimental animals, it might correct the brain GABA deficiency characteristic of Huntington disease. Of six patients treated long enough to be clinically evaluated, one showed marked and two others showed significant improvement. High-dose INH therapy carries serious toxic risks, which are influenced by patients' acetylator phenotypes. Nevertheless, results are sufficiently promising to warrant further controlled trials of INH or other GABA-T inhibitors in Huntington disease.

Amino acids were measured in autopsied brain from two patients who died with a dominantly inherited form of olivopontocerebellar atrophy. Neuropathologic changes found in the brain of these patients suggested a loss of cerebellar climbing fibers. The contents of aspartic acid, gamma-aminobutyric acid, and homocarnosine were reduced in the cerebellar cortex and the. dentate nucleus, while taurine content was markedly elevated in the same brain regions. These findings are compatible with the possibility that aspartic acid is the excitatory synaptic transmitter of the climbing fibers and taurine is the inhibitory neurotransmitter of one or more types of interneurons in the cerebellum.

we compared amino acid contents of 54 epileptogenic foci removed neurosurgically from temporal or frontal cortex of 35 patients with focal epilepsy with those of biopsies from the same cortical regions of 14 nonepileptic patients. Neither taurine nor GABA content was reduced in epileptogenic foci. Glycine content was elevated markedly in some foci, whereas aspartic acid content was normal. Mean glutamic acid content was significantly higher in epileptogenic foci than in control cortex, and six foci contained amounts of glutamate more than 2 SD above the control mean. Our findings do not support hypotheses that deficiencies of taurine or GARA are involved in the pathogenesis of focal epilepsy but do suggest a possible etiologic role for the excitatory neurotransmitter, glutamic acid.

Isoniazid (INH) was given to nine patients with Huntington disease (HD) in a double-blind, placebo-controlled crossover trial. In an earlier open trial, three of six patients had improved, and one of them remained improved after 7 years on INH. Only one patient benefited in the present trial. All patients excreted small amounts of hydrazine in their urine while taking INH, and it is this INH metabolite that elevates GABA content in brain. GABA concentrations were markedly increased in CSF during INH therapy. Lack of clinical improvement in most HD patients despite elevation of brain GABA content suggests that in the minority who are benefited, INH may be acting by some mechanism other than increase of GABAergic neuronal function.