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Context:Proliferation of the use of psychopharmacologic drugs for the treatment of individuals with attention and behavior disorders has promoted discussion of the illicit use of such drugs to enhance academic performance. Previous research has focused on the use of such drugs by undergraduate students; however, inquiry into the nonmedical use of prescription stimulants by medical students is warranted because of the unique qualities of the medical school environment (including academic pressure, stress, and competition with peers) and the demographic characteristics common to many medical students.

Context:Practitioners of manipulative medicine have long sought to prove the intra- and interexaminer reliability of palpatory examinations in assessing somatic dysfunction. However, decades of research have yet to achieve the level of reproducibility needed to satisfy evidence-based criteria.

The article discusses the agreement between Elling Halvorson, owner of Papillon Helicopters and his partners Percassi Group and Gruppo Stilo USA to transform the town of Tusayan, Arizona into a world-class destination resort. It states that Halvorson and his partners are negotiating a zonign and development agreement. It also mentions that their plan coincides with the plan of the Arizona Department of Transportation to expand the local airport of Arizona.

The anterior cruciate ligament (ACL) of the knee and the function of its anteromedial (AM) and posterolateral (PL) bundles are a focus of orthopedic research. Because of the probability that third-year and fourth-year osteopathic medical students will encounter ACL injuries during clinical rotations, it is of paramount importance that students fully understand the functions of the AM and PL bundles as 2 distinct functional components of the ACL. The authors assess the degree to which the AM and PL bundles are discussed within basic science curricula at colleges of osteopathic medicine (COMs). In September 2008, a 6-question survey addressing various aspects of ACL education was mailed to instructors of lower-extremity anatomy at all 28 COMs that existed at that time. Nine of the 21 responding institutions (42.9%) indicated that both the AM and PL bundles of the ACL are discussed within their basic science curricula. Four of these 9 COMs indicated that their instruction mentions that the bundles are parallel in extension and crossed in flexion. Nine of the 21 responding COMs (42.9%) indicated that they instruct students that the AM bundle is a major anterior-posterior restrictor, and 12 (57.1%) indicated that they instruct students that the PL bundle is the major rotational stabilizer of the ACL. In 7 of the 21 responding COMs (33.3%), the AM and PL bundles are identified via direct visualization during anatomic dissection of the ACL. The authors conclude that their findings suggest the need for enhanced presentation of the AM and PL bundles within the basic science curricula at COMs to provide osteopathic medical students with a more comprehensive education in anatomy.

The article focuses on the proposal to develop the Superstition Mountains into a real estate area in Phoenix, Arizona. Having the plans for development of the Superstition Mountains, the author explores the advantages and disadvantages of the real estate development towards the wildlife and environment of Phoenix. He also makes a reference on the possibility for the Superstition Mountains to be like the crowded and polluted image of Superstition Vistas. In addition, he examines the proposals made by the state government for Superstition Mountains, targeting to preserve the wildlife in the city. Furthermore, the author suggests on the need to plan better for the utilization of the land, projecting its transformation into a sustainable area.

The article focuses on the emergence of endangered Mexican gray wolf in the grasslands, mountains and streams of western New Mexico and eastern Arizona. The government's reintroduction rulebook states that a rancher cannot shoot a wolf simply because it threatens the livestocks however, the federal officers may kill or capture the wolf unless it kills three cows or sheep or other domestic animals in a single year. Allegedly, some ranchers said that environmentalists are using the wolf as a terrorist tactic to force ranchers off public lands they have controlled for decades.

The article presents an investigation on the murder of Japanese tourist Tomomi Hanamure near the Havasu Falls, a mile away from the Supai village in Arizona on July 11, 2006. Hanamure was reportedly traveling along the waterfalls to celebrate her 34th birthday alone on May 8, 2006. She was said to be an experienced world traveler who had been hiking the canyon before. Investigations revealed that such murder involves an 18-year-old Randy Redtail Wescogame, who allegedly killed Hanamure during a robbery by stabbing her 29 times in the head, neck, and back. Her dead body was discovered submerged in Havasu Creek, indicating no sexual assault. The murderer was found to have been involved in a methamphetamine abuse, whose father has been convicted of sexual abuse while serving as a policeman.

The article discusses the developments of the once-quiet homeland of the Tohono O'odham Nation in Arizona which was now turned into a police state. Due to illegal drugs and the surge of immigrants from Mexico, the U.S. decided to assign Border Patrol officer. Before, it was only a barbed-wire fence that separates the U.S. and Mexico and no U.S. law enforcement group or Tohono O'odham tribal police are delegated to check documents as people travel in and out at a crossing, the San Miguel Gate. O'odham tribal members, through the San Miguel Gate, enter Mexico to shop at their flea market rather than travel far. Border Patrol officials said some smugglers just drive through the gate, hoping they can enter far enough to deliver narcotics or human.

OBJECTIVE To review recent advances in the prevention of venous thromboembolism (VTE) in acutely ill nonsurgical inpatients.DATA SOURCES A MEDLINE search (1966–March 2005) was done to identify relevant articles relating to prevention of VTE in acutely ill nonsurgical inpatients.STUDY SELECTION AND DATA EXTRACTION Four major prophylaxis trials, one registry, one guideline, and supporting articles representative of the subject matter from the last few years were included.DATA SYNTHESIS Enoxaparin, dalteparin, fondaparinux, and unfractionated heparin 5000 units every 8 hours are effective in reducing the risk of VTE in acutely ill medical patients, but such prophylaxis is currently underused. Barriers to be overcome include recognition of the importance of VTE in this population, definition of the optimal strategy to assess risks, optimal timing of the risk assessment, optimal prophylactic regimen for a given level of risk or disease state, and optimal duration of prophylaxis. We recommend that acutely ill medical inpatients should be risk-stratified early in their hospitalization. At this time, the specific risk-assessment protocol should be derived from the trial(s) of the available formulary agent(s). Decisions about providing prophylaxis must also be made considering anticoagulant contraindications and renal function. Mechanical methods of prophylaxis should be considered as monotherapy only if an anticoagulant contraindication exists. The optimal duration of prophylaxis is not known, but 14 days was used in recent studies.CONCLUSIONS Prophylaxis of VTE in acutely ill medical inpatients is underused. Data provide some guidance for increasing awareness and optimizing patient care.

Focuses on the actions and defenses of school district teachers from liability case in the U.S. Discussion on sovereign immunity; Information on the Paul D. Coverdell Teacher Liability Protection Act under the No Child Left Behind in the country; Discussion on the negligence of employees from liability case.

Focuses on education tort cases in the U.S. Information on the Phillips v. Lincoln County School District case; Discussion on assault and battery as intentional torts; Definition of defamation in tort cases.

OBJECTIVE: To describe the pathogenesis of chronic obstructive pulmonary disease (COPD) and mechanisms of benefit, formulations available, drug costs, pharmacokinetic profiles, and pertinent clinical studies for long-acting β2-agonists.DATA SOURCES: A MEDLINE search was conducted from July 1966 through October 2002.STUDY SELECTION AND DATA EXTRACTION: Pertinent articles related to COPD and long-acting β2-agonists.DATA SYNTHESIS: The incidence and subsequent morbidity and mortality of COPD have increased during the last 4 decades, prompting worldwide initiatives to formulate guidelines to decrease the burden of this disease. COPD is a progressive, irreversible disease state characterized by chronic cough, dyspnea, sputum production, and wheezing, in which no medication has been shown to decrease mortality, excluding oxygen supplementation. Bronchodilators have been a mainstay of COPD treatment through their ability to work by both smooth- and non–smooth-muscle mechanisms. Long-acting β2-agonists (i.e., formoterol, salmeterol) dosed twice daily provide more convenient dosing than 4-times-daily regimens of traditional short-acting bronchodilators. Both formoterol and salmeterol have acceptable adverse event profiles when used at recommended doses. There have been no direct clinical outcome studies comparing formoterol and salmeterol, but both have shown some benefits over ipratropium and theophylline in improving the symptoms, spirometric indices, exacerbations, and quality of life of patients with COPD.CONCLUSIONS: Based on current evidence, long-acting β2-agonists are acceptable first-line agents for patients with COPD.

OBJECTIVE: To evaluate the role of risedronate in corticosteroid-induced osteoporosis.DATA SOURCES: Clinical literature was accessed through MEDLINE (1966–February 2001). Key search terms included risedronate, corticosteroid, osteoporosis, and bisphosphonate.DATA SYNTHESIS: Corticosteroid-induced osteoporosis (CIO) is clinically challenging and can lead to fractures. Risedronate, an oral bisphosphonate, has been studied for use in CIO. Trials focusing on the use of risedronate in these patients were reviewed.CONCLUSIONS: Risedronate 5 mg/d increased bone mineral density at lumbar, femoral neck, and trochanter skeletal sites in patients recently initiated on or receiving long-term corticosteroid therapy. Further investigation is needed to determine risedronate's effects on fracture prevention. The drug was well tolerated.

1Presynaptic varicosities of the model neuronal cell line NG108–15, a cholinergic neuroblastoma cell × glioma cell hybrid capable of innervating striated myotubes, were examined for the presence of inositol 1,4,5‐trisphosphate (IP3)‐sensitive and Ca2+‐activated (ryanodine‐sensitive) Ca2+stores using confocal microscopic imaging of Ca2+‐sensitive fluorescent dye loaded into the cells.2Initial demonstration of the presence of IP3receptors and ryanodine receptors in the NG108–15 varicosities was obtained using immunocytochemistry.3Treatment of NG108–15 cells with bradykinin (0.1 μM), whose receptor is linked to IP3generation, and separately, caffeine (10 mM), an activator of endoplasmic reticulum ryanodine receptors, resulted in substantial increases in [Ca2+]iin the varicosities.4K+‐evoked changes in [Ca2+]iin the varicosities were reduced (52 %) after emptying the ryanodine‐sensitive Ca2+store using caffeine (10 mM), but were not affected by prior depletion of the IP3‐sensitive Ca2+store using thapsigargin (1 μM).5Bradykinin‐induced changes in [Ca2+]iwere abolished following depletion of the IP3‐sensitive Ca2+store using thapsigargin (1 μM) and were reduced (72 %) by prior emptying of the ryanodine‐sensitive Ca2+store with caffeine (10 mM).6The same results were obtained when the varicosities of the NG108–15 cells had formed synaptic junctions with co‐cultured rat hindlimb myotubes.7Taken together, the results suggest that, in the varicosities, activation of the IP3pathway evoked the release of Ca2+from the IP3‐sensitive store, which, in turn, secondarily induced the release of Ca2+from the ryanodine‐sensitive store via Ca2+‐induced Ca2+release, and that depolarization‐induced Ca2+entry evoked Ca2+‐induced Ca2+release only from the ryanodine‐sensitive store. Thus, functional internal Ca2+stores are inherent components of presynaptic varicosities in this neural cell line.

Fas ligand (FasL)-dependent apoptosis has been implicated in the control of tissue-damaging inflammatory responses in several immune privileged sites. Here, we present data demonstrating that FasL is expressed on human trophoblast cells throughout pregnancy and transduces growth inhibitory/death signals in cells bearing its receptor, Fas (CD95). Immunohistochemical analysis detected FasL-positive staining in the trophoblast layer of villi of first- and second-trimester and term (no labor) placental tissues, as well as in freshly isolated cytotrophoblasts representing these gestational ages. In contrast, term placental tissues and cytotrophoblasts from labor-associated deliveries exhibited significantly reduced FasL expression, suggesting that parturition altered the characteristics of trophoblast cells. FasL-specific immunoblotting of cytotrophoblast cell lysates further confirmed these results. To assess the functionality of FasL expressed on cytotrophoblasts, we co-cultured these cells with Fas-bearing Jurkat T cells. Cytotrophoblasts from early pregnancy, or term with no labor, significantly inhibited growth in Jurkat cells, evident even at a 11 effectortarget cell ratio, as determined by the incorporation of 3Hthymidine. Similar results were obtained when a FasL-positive colon carcinoma cell line, SW620, was used in place of cytotrophoblasts. In contrast, term cytotrophoblasts from labor deliveries exhibited poor FasL expression and were quantitatively much less proficient in inhibiting 3Hthymidine incorporation in Jurkat cells. These data indicate that FasL could participate in modulating the inflammatory responses associated with labor and suggest intrinsic molecular differences in the placental microenvironment before and after labor .

Recent data suggesting complex I dysfunction in Parkinson's disease (PD) arises from mitochondrial DNA (mtDNA) mutation does not conclusively answer whether the responsible genetic lesion is inherited (primary) or somatic (secondary). To address this question, we identified a family in which multiple members over three generations are affected with PD through exclusively maternal lines. Cytoplasmic hybrids (cybrids) were created for 15 family members over two generations by trnsferring each individual's mtDNA to mtDNA‐depleted human neuroblastoma cells. Eight of the 15 cybrid lines contained mtDNA obtained from maternally descended family members and seven contained mtDNA from paternally descended family members. After 6 weeks of culture, cybrid cell lines were assayed for complex I activity and oxidative stress, and mitochondrial morphology was analyzed by electron microscopy. Compared with the cybrid lines containing mtDNA from paternal descendants, cybrid lines containing mtDNA from maternal descendants had lower complex I activity, increased reactive oxygen species production, increased radical scavenging enzyme activities, and more abnormal mitochondrial morphologic features. These findings were present in cybrid lines containing mtDNA from maternal descendants with PD as well as in currently asymptomatic young maternal descendants, and support a precedent for inherited mtDNA mutation in some persons with PD.

This study tested the hypothesis that the pacing of suggestions to phases of the breathing cycle can enhance responding in hypnosis. Ninety-six subjects at three levels of hypnotizability responded to suggestions for coolness/numbness and arm lightness/levitation both paced and counter-paced to the phase of breathing (inhalation) claimed to enhance responding to them. As a test of pacing as a technique for indirect hypnosis, the covert pacing of such suggestions was compared to overt pacing. Results failed to demonstrate a relationship between the pacing of the phases of breathing and its hypothesized effects. Responding to suggestions was related to level of hypnotizability and an interaction was noted between overtness/covertness of pacing and level of hypnotizability.

The problem: How to get the most for the electric utility industry's research and development dollar. The answer, an ambitious and innovative one, was initiated by the utilities themselves when they founded the Electric Power Research Institute (EPRI) in 1973. EPRI's charter — to develop new and improved technology for environmentally acceptable production, transmission, and distribution of electric power to help the utility industry meet present and future electric energy needs.

The Ah receptor binds aryl hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with high affinity. After binding aryl hydrocarbons, the receptor releases the 90-kDa heat shock protein and forms a dimer with the Arnt protein capable of binding at xenobiotic-responsive elements (XREs) and stimulating the transcription of genes involved in the metabolism of aryl hydrocarbons. The activity of the Ah receptor/Arnt dimer can be decreased by treatments causing the down-regulation of protein kinase C and decreasing the nuclear accumulation of the receptor. Incubation with acid phosphatase or with alkaline phosphatase has been reported to block XRE binding. Thus the literature suggests that phosphorylation regulates Ah receptor activity by affecting DNA binding and/or nuclear transport. A reporter plasmid containing two XREs was used to investigate the effects of phosphatase inhibitors on TCDD-dependent transcription by the Hepa-1 mouse liver cell line. The inhibitors calyculin A and okadaic acid caused two- to threefold increases in TCDD-dependent transcription at concentrations capable of selectively inhibiting protein phosphatase 1 and protein phosphatase 2A . The inhibitor cyclosporin A doubled TCDD-dependent transcription at a concentration capable of selectively inhibiting protein phosphatase 2B. All three of the phosphatase inhibitors increased TCDD-dependent transcription without affecting transcription in the absence of TCDD. Nuclear extracts were prepared from cells treated with concentrations of okadaic acid or cyclosporin A which substantially stimulated TCDD-dependent transcription. Neither of the inhibitors significantly increased the level of TCDD-dependent XRE binding in the extracts. GAL4–Arnt fusion proteins were used to further investigate whether the phosphatase inhibitors affected a step other than DNA binding. Okadaic acid treatment specifically increased the ability of a GAL4 fusion protein containing the Arnt PAS and transactivation domains to stimulate transcription. These results suggest that serine/threonine-specific protein phosphatases can act at a level subsequent to XRE binding to inhibit the ability of the Ah receptor/Arnt dimer to stimulate transcription.

To determine whether the production of brain ischemia is modified by antiplatelet agents administered at the time of extracranial endothelial injury, we modified a four-vessel occlusion rat model so that an electrogenic platelet thrombus in one carotid artery produced cerebral ischemia. DC current was passed through an anode around the left carotid artery of 11 rats with preoccluded vertebral and contralateral carotid arteries. Five of six untreated rats became unresponsive because of carotid occlusion and resultant cerebral ischemia; none of five animals pretreated with indomethacin and infused with prostacyclin (PGI2) were clinically affected. Light-and electronmicroscopic studies showed arterial platelet-fibrin thrombi and ischemic brain damage in untreated rats. All rats had received radiolabeled platelets; radioactivity was increased in the electrogenically injured left carotid arteries from treated and untreated rats, but counts were reduced by more than 80 in indomethacin/ PGL2-treated rats (p< 0.01).

Male weanling rats were raised on diets based on torula yeast which were deficient in vitamin E and selenium, or supplemented with these substances. They were injected intraperitoneally with sodium selenite at 2 mg Se/kg or with sodium sulfite to give the same level of sodium. Following injection, lipid peroxidation in vivowas estimated by monitoring the production of ethane, a volatile product formed on the peroxidation of ω-3-unsaturated fatty acids. In the hour following injection, vitamin E- and selenium-deficient rats injected with selenite produced 15 times as much ethane as did controls injected with sulfite. All rats in this group died from 1 to 4 hr after injection. Rats fed diets supplemented with selenite showed only a two- to threefold stimulation of ethane production by selenite and 3/4 survived. Rats fed diets supplemented with vitamin E did not produce more ethane in response to selenite injection and 3/4 survived. All four rats supplemented with both vitamin E and selenium survived without showing increased ethane production. Thus, the increased vulnerability of vitamin E- and selenium-deficient rats to acute selenite toxicity may involve peroxidation in vivo.Rats fed diets supplemented with vitamin E could survive at least twice as much selenite as rats deficient in selenium and vitamin E. Seven-day survival figures for rats fed the basal diet and injected with selenite were: 1 mg Se/kg, 7/8; 2 mg Se/kg, 0/8. For rats supplemented with vitamin E the figures were 2 mg Se/kg, 7/8; 4 mg Se/kg, 2/8. When sodium selenate was injected into rats deficient in vitamin E and selenium at 3 mg Se/kg it caused acute mortality without increasing peroxidation in vivo.

Copper sulfate injected intraperitoneally at a dose of 2 mg Cu/kg into vitamin E-and selenium-deficient rats caused a sixfold increase in the formation in vivoof the lipid peroxidation product ethane, and caused acute mortality in 4/5 rats. Selenium supplementation of the diet at 0.5 ppm Se largely prevented the increase in ethane production caused by copper injection and reduced mortality to 1/5 rats. Vitamin E supplementation of the diet at 200 IU/kg fully eliminated the increase in ethane production caused by copper injection, and completely prevented mortality. Vitamin E-deficient rats injected with copper sulfate at 5 mg Cu/kg produced over 10 times the ethane produced by rats injected with sodium sulfate or left uninjected. The ethylene produced by the rats injected with copper sulfate was 5% of the ethane produced, and did not differ significantly from the ethylene produced by the controls. Adding copper sulfate at 5 ppm Cu to a liver homogenate stimulated the production of ethane but not of ethylene. The correlation of increased ethane production with increased mortality suggests that lipid peroxidation may be important in the increased toxicity of copper in vitamin E- and selenium-deficient rats.

We studied 10 patients who survived for 2 to 8 weeks in a vegetative state, including 8 with cardiopulmonary failure and 2 with subarachnoid hemorrhage. Within days of onset, they regained brainstem function and awoke, but none had evidence of cognitive awareness. All patients opened their eyes within 2 weeks, and eight had roving conjugate eye movements. Pupillary and corneal responses were intact within 1 week, and seven patients had tonic oculovestibular responses (OVR) within 24 hours. By the end of 1 day, only three patients failed to move limbs in response to noxious stimuli. At postmortem, all patients had widespread ischemic neuronal damage in the cerebral hemispheres. The brainstems lacked morphologic abnormality, except that one patient had a single microinfarct in the superior colliculus.

Of 217 patients with clinical diagnosis of acute stroke 23 had nonischemic lesions diagnosed by computed tomography (CT) or lumbar puncture (LP). CT demonstrated all 37 cases of intracerebral hemorrhagic lesions; 9 were detected by LP. CT failed to demonstrate 8 of 17 cases of subarachnoid hemorrhage, but only 1 of these lacked headache or stiff neck.

The study assessed Jencks' claim that responses to certain suggestions are enhanced by being paced with different phases of the breathing cycle. Following hypnotic induction, twenty-four subjects were given four treatments in counterbalanced order: 1) exhalation-enhanced suggestions paced to exhalation, 2) inhalation-enhanced suggestions paced to inhalation, 3) inhalation-enhanced suggestions counterpaced to exhalation, and 4) exhalation-enhanced suggestions counterpaced to inhalation. Subjects' reports of imagery vividness provided marginal support (p< .06) for Jencks' hypothesis. Post-experimental inquiry indicated subjects were unaware of the breathing contingency. Results suggest that appropriate pacing may make a greater difference for the energy-confidence group of suggestions (inhalation-paced) than for the calm-relaxation group (exhalation-paced).

The effects of intraperitoneally injected ferrous chloride and iron-dextran on lipid peroxidation in vivo were assessed. Peroxidation was estimated by measuring ethane, a volatile autoxidation product of omega-3-unsaturated fatty acids. Rats supplemented with 0.1 ppm dietary selenium and rats supplemented with 0.1 ppm selenium and 200 iu vitamin E/kg diet were injected with ferrous chloride at 30 mg iron/kg, or with sodium chloride, or left uninjected. In both dietary groups ferrous chloride increased ethane production while sodium chloride did not, but the iron-caused ethane increase was 8 times greater in the low E group. Iron-dextran injected at 500 mg iron/kg was fatal to rats fed a basal diet deficient in selenium and vitamin E or a diet supplemented with 0.5 ppm selenium; supplemental vitamin E at 200 iu/kg diet prevented this mortality. Iron-dextran quadrupled ethane production in rats fed the basal diet and tripled ethane production in rats fed the selenium-supplemented diet. Vitamin E supplementation prevented the iron-dextran-caused rise in ethane production. A histological examination of rats killed by iron-dextran showed severe generalized necrosis of the diaphragm and severe focal necrosis of thigh muscle. Vitamin E protected more effectively than selenium against iron-dextran-caused peroxidation as well as against acute iron-dextran-caused mortality.

For over a decade the human factors of Remotely Piloted Aircraft Systems (RPAS, but also known as Unmanned Aerial Systems-UAS or Unmanned Aerial Vehicles –UAV) has been the continued focus of a community of scientists and engineers. Their efforts have been highlighted in various workshops, conferences and books and range from the design of effective ground control stations to crew coordination, spatial disorientation, supervisory control of multiple vehicles, soda straw views of camera feed, and training and selection. Much progress has been made. But new problems are surfacing of a different, more complex nature. Current pressing issues such as the integration of UAS in the national airspace, training and certification of civilian pilots, or exploitation of sensor data from these platforms and concomitant privacy concerns fall within the scope of the discipline of Human Systems Integration (HSI). This panel will highlight several human systems integrations issues surrounding RPAS and will engage the audience in discussion of those issues.

There is continuing evidence of a disparity between the level of educational sophistication (that is, the validity and rigor of the equation “models” by which members of the scientific and engineering communities apply analytical logic to a world of nonpersonal technological problems) and the empirical, immature, and Aristotelian semantic notions entangling and invalidating the often benighted “models” they use in a Second World, the day-to-day world of people, organizations, and people-problems.

This article discusses an episode of mustiness that was extremely resistant to treatment processes, which occurred on the Cedar River in Iowa during June through July, 1961. A study was done on the chemical characteristics of the metabolic products of actinomycetes isolated and cultured from the Cedar River during the 1961 period of musty taste. The difficulty of analysis, effect of cultural conditions, isolation procedures and actinomycete‐produced substances are all discussed, along with neutral‐fraction characteristics, further purification, constituents of eluate, and infrared analysis. An illustration of the similarity between organic materials of river water and extracted actinomycete metabolites is provided in a comparison of the infrared spectra of an extract of musty Cedar River water, and an extract of the laboratory‐cultured actinomycetes.

Responding by rats was reinforced by intravenous infusions of 0.5 mg/kg methamphetamine hydrochloride. The effects of intraperitoneal injections of various doses of methamphetamine, alpha-methyl-para-tyrosine (AMPT) and 3, 4-dihydroxyphenylalanine (1-DOPA) were determined on this baseline. Intraperitoneally-administered methamphetamine produced a dose-related pause in responding, apparently indicating drug satiation. Injections of AMPT caused responding either to increase at low doses, or, at intermediate and high doses, to increase, then cease altogether, and finally return at a high rate which decreases to baseline. Injections of 1-DOPA had no noticeable effect on drug responding. Some biochemical implications of these data were discussed.

DIAGNOSIS: DARIER'S DISEASE. PRESENTED BY DR. S. M. PECK. HISTORY.— A 41-year-old female. Skin eruption of about 35 years' duration. This patient has been under observation continuously since 1942. She has always noted that exposure to strong sunlight would cause a flare of her skin eruption on exposed areas. In 1952, after a summer vacation, there was a marked exacerbation of lesions with appearance on the face suggestive of L.E. FAMILY HISTORY.— A niece also had Darier's disease. LABORATORY FINDINGS.— Essentially normal including blood cholesterol, blood sugar, etc. Vitamin A levels taken when she was first seen with the method then available showed inadequate response to ingestion of vitamin A in fairly large doses. Skin biopsy was compatible with the diagnosis of Darier's disease. CLINICAL COURSE.— She has been under continuous vitamin A therapy in doses of 150,000 units a day per os, and at times this had to be

Recently, an attempt was made to evaluate the antipruritic effect of an analgesic drug. Some of the problems encountered will be discussed, and a blueprint for the proper clinical investigation of antipruritic drugs will be presented.Experimental ProcedureIn previous animal experiments, the drug was found to depress the perception of cutaneous stimuli. In addition, it was found to have potent local anesthetic activity, mild antihistaminic action, and potentiation of analgesia.The case material consisted of patients with severe chronic pruritus. In a pilot study on 23 patients, the drug showed considerable promise, and a subsequently administered placebo was ineffective. The experiment was then continued with 79 additional cases, with use of a carefully planned, double-blind, randomized technique. Statistical analysis of the complete data demonstrated that the test drug was not superior to the placebo. Appreciation of the difficulties and pitfalls inherent in the study led to a

During the nineteenth century Latin America produced a significant number of thinkers and philosophers who recognized that their countries were failing to keep pace with Western Europe and the United States in material progress, social equality and political stability. Some of these men were primarily abstract thinkers, but many were politically active and exercised considerable influence through their writing. Juan Bautista Alberdi, an Argentine, was a member of the latter group whose ideas are still discussed frequently today.

Beloff and Peters,1 in a study of thermal burns, first suggested the possibility that bullous formation may be mediated by proteolytic enzymes. Stoughton2 produced enzymatic cytolysis in formalin-fixed epidermis with a factor obtained from fecal filtrates of patients with ulcerative colitis; acantholysis, separation of epithelial cells, and subsequent blister formation were observed. The histologic findings were "very similar to those of pemphigus vulgaris." In a later study, Stoughton and Novak3 reported that mild heat damage resulted in enzymatic disruption of tonofibrils and intercellular bridges in human epidermis.Cliffton4 has reported increased antiproteolytic activity in the serum of patients with extensive carcinomatosis. In this connection, pemphigus-like eruptions have been observed in patients with thoracic or abdominal carcinoma.Consideration of the above findings suggests that pemphigus bullae may be produced by action of proteolytic enzymes on epidermis; this possibility

Objective: To review the spectrum of activity, efficacy, safety, and role in therapy of all antibiotics and related biologics approved by the Food and Drug Administration (FDA) in the last decade.Data Sources: A literature search was performed using PubMed and Google Scholar (2010 to end May 2021) with the search terms’ name of the antibiotic or the biologic. Data were also obtained from the prescribing information, FDA, and ClinicalTrials.gov websites.Study Selection: All relevant English-language, late phase clinical trials assessing the safety and efficacy of the identified drugs were included. Review articles and references of retrieved articles were evaluated for relevant data.Data Synthesis: Antibiotic resistance is a public health crisis, and antibiotic development is imperative to outpace the ability of bacteria to develop resistance. Only 17 new systemic antibiotics and 1 related biologic have been approved by the FDA since 2010. Among these drugs, 14 were approved for common bacterial infections, 1 was approved for Clostridioides difficileinfection (CDI), 1 was licensed to prevent CDI recurrence, and 2 were approved for drug-resistant tuberculosis. Very few antibiotics are in clinical development.Relevance to Patient Care and Clinical Practice: The arrival of these new antibiotics was welcomed with great enthusiasm, particularly when they met previously unmet medical needs. Unfortunately, the majority of them represent modifications to existing chemical structures rather than new drug classes. Despite the availability of these antibiotics, managing patients with deep-seated infections and those with extensively resistant gram-negative organisms remains challenging.Conclusions: The number of new antibiotics and their indications are not keeping up with resistance and the needs of the patients.

The complications associated with lumbar puncture LP were compared in 2 groups of 342 patients. The first group of patients was anticoagulated after the LP, and the second was not. The incidence of minor headache or back pain was similar in the 2 groups Group 162, Group 264. The anticoagulated patients had a higher incidence of paraparesis Group 1, 5 patients, Group 2, No patientsp< .05 and severe back or lumbosacral radicular pain lasting more than 48 hours Group 1, 18 patients, Group 2, 6 patientsp< .025. Seven of the anticoagulated patients developed spinal hematomas 5 with paraparesis, 2 with severe back pain. Among the anticoagulated patients the risk of a major complication was increased by a traumatic LP p< .001, starting anticoagulation within one hour of the LP p< .001, or aspirin treatment at the time of the LP p< .001. This study suggests that if LP is done, delaying anticoagulation for at least one hour and avoiding concurrent aspirin therapy may decrease the risk of developing an extraparenchymal spinal hematoma.