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Background: Patients with asthma are interested in the use of breathing exercises but their role is uncertain. The effects of the Buteyko breathing technique, a device which mimics pranayama (a [...]

Background: This study evaluated the union rate of talar neck fractures with substantial bone defects treated acutely with autologous tibial bone graft during primary osteosynthesis.Methods: A case series at a level 1 trauma center was performed to identify consecutive patients who underwent operative fixation of talar neck fracture with autograft (Current Procedural Terminologycodes 28445 and 20902) between 2015 and 2018. “Substantial bone defect” was defined as a gap greater than 5 mm in the sagittal plane and greater than one-third of width of the talar neck in the coronal plane. Postoperative foot computed tomographic (CT) scans were obtained for all patients. Primary outcome was union, and secondary outcomes were malunion, avascular necrosis (AVN), post-traumatic arthritis (PTA), and patient-reported outcomes (PROs).Results: Twelve patients with 12 fractures were included in the series, with an average length of follow-up of 26 months (range: 7-55) The average age was 34 years (17-59), and the most common mechanism of injury was motor vehicle crash. The Hawkins classification of the fractures was 4 type II (2 type IIA and 2 type IIB) (33%) and 8 type III (67%). Four fractures (33%) were open fractures. Union was achieved in 11 patients (92%). There was 1 malunion (8%). AVN was identified on postoperative CT scans in 11 patients (92%). Three of these 11 eventually showed collapse. Ten patients (83%) had radiographic evidence of some degree of ankle PTA, and 12 patients (100%) had radiographic evidence of some degree of subtalar PTA. Average Patient-Reported Outcomes Measurement Information System–Short Form score was 37 (32-45) and average Foot and Ankle Ability Measure activities of daily living and sports subscale scores were, respectively, 61 (31-87) and 31 (0-71), respectively. Average visual analog scale score was 5 (0-10), and average Foot Function Index was 49 (7-89). SF-36 scores showed fair to poor outcomes in the majority of patients.Conclusion: In this relatively small series, tibial autograft in primary osteosynthesis of comminuted talar neck fractures with substantial bone defects is associated with excellent union rates and low malunion rates. Despite high union rates, secondary outcomes of AVN with or without collapse, ankle and subtalar PTA, and relatively low PROs were common.Level of Evidence: Level IV, case series.

The blood-brain barrier (BBB) and blood-cerebrospinal fluid (BCSF) barriers are critical determinants of CNS homeostasis. Additionally, the BBB and BCSF barriers are formidable obstacles to effective CNS drug delivery. These brain barrier sites express putative influx and efflux transporters that precisely control permeation of circulating solutes including drugs. The study of transporters has enabled a shift away from “brute force” approaches to delivering drugs by physically circumventing brain barriers towards chemical approaches that can target specific compounds of the BBB and/or BCSF barrier. However, our understanding of transporters at the BBB and BCSF barriers has primarily focused on understanding efflux transporters that efficiently prevent drugs from attaining therapeutic concentrations in the CNS. Recently, through the characterization of multiple endogenously expressed uptake transporters, this paradigm has shifted to the study of brain transporter targets that can facilitate drug delivery (i.e., influx transporters). Additionally, signaling pathways and trafficking mechanisms have been identified for several endogenous BBB/BCSF transporters, thereby offering even more opportunities to understand how transporters can be exploited for optimization of CNS drug delivery. This review presents an overview of the BBB and BCSF barrier as well as the many families of transporters functionally expressed at these barrier sites. Furthermore, we present an overview of various strategies that have been designed and utilized to deliver therapeutic agents to the brain with a particular emphasis on those approaches that directly target endogenous BBB/BCSF barrier transporters.

Metformin, a widely used anti-hyperglycemic drug in the biguanide class, is currently under investigation for the prevention of cancer. Surprisingly however, considering the time and cost of clinical chemoprevention trials and the current scrutiny of cancer chemoprevention, limited attention has been given to integrating available data, identifying the subpopulations most likely to benefit, or to quantitatively understanding the potential pitfalls of biguanide chemoprevention. Herein, a physiologically-based pharmacokinetic (PBPK) and pharmacodynamic framework is proposed for integrating information on physicochemical, cell-based, animal, and human studies of various biguanides to identify gaps in knowledge and to build a systems model that may facilitate the planning of randomized cancer chemoprevention trials of metformin.

Introduction: Sports participation, while offering numerous developmental benefits for adolescents, has been associated with alcohol use in prior research. However, the relationship between sports participation and alcohol use among adolescents remains unclear, particularly how research design elements impact evidence of this relationship. We reviewed the evidence regarding sports participation and alcohol use among adolescents, with a focus on examining the potential impact of research design elements on this evidence. Methods: Studies were assessed for eligibility and coded based on research design elements including: study design, sampling method, sample size, and measures of sports participation and alcohol use. Results: Fifty-four studies were assessed for eligibility, 29 of which were included in the review. Nearly two-thirds used a cross-sectional design and a random sampling method, with sample sizes ranging from 178 to 50,168 adolescents (Median = 1,769). Sixteen studies used a categorical measure of sports participation, while 7 applied an index-type measure and 6 employed some other measure of sports participation. Most studies assessed alcohol-related behaviors (n = 18) through categorical measures, while only 6 applied frequency only measures of alcohol use, 1 study applied quantity only measures, and 3 studies used quantity and frequency measures. Conclusions: Sports participation has been defined and measured in various ways, most of which do not differentiate between interscholastic and community-based contexts, confounding this relationship. Stronger measures of both sports participation and alcohol use need to be applied in future studies to advance our understanding of this relationship among youths.

The latitudinal sound-speed structure of the Sun's convection zone gives insight into the physical processes occurring there, specifically the cellular convection and possibly the presence of magnetic fields. Using helioseismic data from the GONG network and MDI instrument on SOHO, we map the latitudinal acoustic structure of the convection zone from 1995 to 2002. The temporally averaged structure confirms previous findings of an excess in sound speed at the $10^{-4}$ level at 60 degrees latitude. There also appear to be some variation with time, with the peak in sound-speed asphericity at 60 degrees growing towards the maximum of solar activity according to the MDI data. However, we present some evidence that such variation may be associated with instrumental variation between the epochs before and after SOHO was temporarily lost in 1998. Nonetheless, some genuine temporal variation may be present, and we discuss the possible physical causes of that.

Ferritin is traditionally considered a cytoplasmic iron-storage protein, but recent reports indicate that it is also found in cell nuclei. Nuclear ferritin has been proposed to be involved in both the protection of DNA and the exacerbation of iron-induced oxidative damage to DNA. We demonstrate that H-rich ferritin is present in the nucleus of human astrocytoma tumor cells. To study the mechanism and regulation of ferritin translocation to the nucleus, we developed a cell culture model using SW1088 human astrocytoma cells. Changes in cellular iron levels, cytokine treatments and hydrogen peroxide exposure affected the distribution of ferritin between the cytosol and the nucleus. Ferritin enters the nucleus via active transport through the nuclear pore and does not require NLS-bearing cytosolic factors for transport. Furthermore, H-rich ferritin is preferred over L-rich ferritin for uptake into the nucleus. Whole cell crosslinking studies revealed that ferritin is associated with DNA. Ferritin protected DNA from iron-induced oxidative damage in both in vitro and in cell culture models. These results strongly suggest a novel role for ferritin in nuclear protection. This work should lead to novel characterization of ferritin functions in the context of genomic stability and may have unparalleled biological significance in terms of the accessibility of metals to DNA. The knowledge generated as a result of these studies will also improve our understanding of iron-induced damage of nuclear constituents.

These studies report on the activation and induction of cGMP-dependent protein kinase (PKG) by exisulind and analogs and test the hypothesis that PKG is involved in the induction of apoptosis in colon tumor cells. Exisulind and analogs are proapoptotic drugs developed as inhibitors of cGMP phosphodiesterase gene families 5 and 2 that have been shown to sustain increased cGMP in SW480 and HT29 cells. At concentrations that induced apoptosis, both exisulind and CP461 increased PKG activity in SW480 cell supernatants. PKG activation was dose-dependent and sustained. Activation of PKG by exisulind and analogs was also seen in the colon tumor cell lines HT29, T84, and HCT116. The guanylyl cyclase activators YC-1 and guanylin increased PKG activity secondary to increased cellular cGMP and induced apoptosis in colon tumor cells. Exisulind and CP461 had no direct effect on purified PKG activity or on basal and stimulated PKG activity from cell supernatants. An additional effect of exisulind after 8 h of drug treatment was a dose-dependent increase of PKG Ibeta protein expression. beta-Catenin, a potential new substrate for PKG, whose regulation influences apoptosis, was phosphorylated by PKG in vitro. 32P-labeled cells treated with exisulind showed increased phosphorylation of beta-catenin. These data indicate that exisulind and analogs activate and induce PKG, resulting in increased phosphorylation of beta-catenin and enhanced apoptosis to promote colon tumor cell death.

BACKGROUND AND AIMS: Helicobacter pylori is a major cause of peptic ulcers and gastric cancer. Vaccine development is progressing but there is concern that immunisation may exacerbate Helicobacter induced gastritis: prophylactic immunisation followed by challenge with H felis or H pylori can induce a more severe gastritis in mice than seen with infection alone. The aim of this study was to investigate the relationship between immunity to Helicobacter infection and post-immunisation gastritis. METHODS: (1) C57BL/6 mice were prophylactically immunised before challenge with either H felis or H pylori. Histopathology and colonisation were assessed one month post-challenge. (2) C57BL/6 mice were prophylactically immunised against H felis infection and gastritis assessed up to 18 months post-challenge. RESULTS: Prophylactic immunisation induced a reduction in bacterial colonisation following H felis challenge which was associated with increased severity of active gastritis with neutrophil infiltration and atrophy. However, immunised mice challenged with H pylori SS1 had little evidence of pathology. Long term follow up showed that post-immunisation gastritis was evident at three months. However, from six months onwards, although immunised/challenged mice still developed gastritis, there was no significant difference between inflammation in these mice and infected controls. Post-immunisation gastritis was not associated with the serum antibody response. Immunisation prevented the formation of secondary lymphoid aggregates in the gastric tissue. CONCLUSION: The H felis mouse model of post-immunisation gastritis is the most extreme example of this type of pathology. We have shown in this model that post-immunisation gastritis is a transient event which does not produce long term exacerbation of pathology.

Myofibroblasts, characterised by high expression of alpha-smooth muscle actin (alpha-SMA), are important and transient cells in normal wound healing but are found in increased number in various pathological conditions of the lung including asthma and pulmonary fibrosis. The mechanisms that regulate the myofibroblast phenotype are unknown but are likely to involve signals from the extracellular matrix transmitted via specific integrins. Vitronectin is a glycoprotein released during inflammation and has been shown to regulate the phenotype of vascular smooth muscle cells via alpha v and beta 1 integrins. In the current study we have examined whether vitronectin influences the phenotype and function of normal human lung fibroblasts (HFL-1). Incubation of HFL-1 cells with vitronectin induced a concentration-dependent reduction in alpha-SMA expression. By contrast, function-blocking monoclonal antibodies to the vitronectin integrins alpha v, beta 1, alpha v beta 3 and alpha v beta 5 induced the expression of alpha-SMA and its organization into stress fibers. Expression of alpha-SMA induced by all function-blocking monoclonal antibodies was abrogated by inhibition of protein kinase C and phosphatidylinositol-3 kinase, but the effects of inhibition of other signalling pathways was integrin dependent. Exposure to other extracellular matrix proteins such as fibronectin, collagen or their integrins did not influence expression of alpha-SMA. The expression and organization of alpha-SMA induced by exposure to function-blocking antibodies was translated into an augmented capacity of HFL-1 cells to contract fibroblast populated collagen gels. By contrast, contraction of collagen gels following incubation with vitronectin was not significantly different to control. This study has shown that vitronectin influences the phenotype and behaviour of HFL-1 cells by downregulating the expression of alpha-SMA and reducing their contractile ability. By contrast, occupancy of specific integrins by function-blocking antibodies upregulated the expression of alpha-SMA and induced the formation of functional stress fibers capable of contracting collagen gels. These results suggest that vitronectin modulates the fibroblast-myofibroblast phenotype, implying an important role in the remodelling process during lung development or response to injury.

We describe the rational design and synthesis of B- and A,B-ring-modified camptothecins. The key α-hydroxy-δ-lactone pharmacophore in 7-tert-butyldimethylsilyl-10-hydroxycamptothecin (DB-67, 14) displays superior stability in human blood when compared with clinically relevant camptothecin analogues. In human blood 14 displayed a t1/2 of 130 min and a percent lactone at equilibrium value of 30%. The tert-butyldimethylsilyl group renders the new agent 25-times more lipophilic than camptothecin, and 14 is readily incorporated, as its active lactone form, into cellular and liposomal bilayers. In addition, the dual 7-alkylsilyl and 10-hydroxy substitution in 14 enhances drug stability in the presence of human serum albumin. Thus, the net lipophilicity and the altered human serum albumin interactions together function to promote the enhanced blood stability. In vitro cytotoxicity assays using multiple different cell lines derived from eight distinct tumor types indicate that 14 is of comparable potency to camptothecin and 10-hydroxycamptothecin, as well as the FDA-approved camptothecin analogues topotecan and CPT-11. In addition, cell-free cleavage assays reveal that 14 is highly active and forms more stable top1 cleavage complexes than camptothecin or SN-38. The impressive blood stability and cytotoxicity profiles for 14 strongly suggest that it is an excellent candidate for additional in vivo pharmacological and efficacy studies.

Recently, portable C‐arm systems have been developed for cardiac studies. While these systems have been used at a number of centers on a small scale for procedures in the operating room, emergency room, or intensive care unit, there are no published data on the performance of the system under more demanding circumstances. Theoretically, a reliable portable C‐arm system could provide a low‐cost alternative to a fixed system in centers with limited resources, such as in developing countries. To test whether a portable C‐arm system could substitute for a permanent laboratory for cardiac catheterization and interventional procedures, we used a C‐arm system as our sole catheterization laboratory for a period of 3 months. The system's performance was compared to a comparable time period using a fixed catheterization laboratory system. The portable system was used to perform 222 procedures (36 interventional and 186 diagnostic), as compared to 236 procedures (30 interventional and 206 diagnostic) with the fixed lab during a comparable time period the preceding year. Although the image quality of the portable system was not as good as with the fixed laboratory, all procedures were performed successfully, with no difference in fluoroscopic time, radiation exposure to the patient, procedure related complications, or clinical restenosis at 1 year. However, radiation exposure to staff was greater, possibly due to the lack of shielding in the temporary lab and the need for the technician to remain close to the unit to set up views. Our results suggest that a portable C‐arm system, while subject to some limitations, can perform as a general catheterization laboratory for diagnostic and interventional procedures.

OBJECTIVE: To establish whether people exposed to drinking water contaminated with 20 tonnes of aluminium sulphate in the Camelford area of Cornwall in the south west of England in July 1988 had suffered organic brain damage as opposed to psychological trauma only. DESIGN: Retrospective study of affected people. Participants: 55 affected people and 15 siblings nearest in age to one of the group but who had not been exposed to the contaminated water were studied. MAIN OUTCOME MEASURES: Various clinical and psychological tests to determine medical condition and anxiety levels in affected people. Assessment of premorbid IQ (pFSIQ) with the national adult reading test, a computerised battery of psychomotor testing, and measurement of the difference in latencies between the flash and pattern visual evoked potentials in all participants. RESULTS: The mean (SE) pFSIQ was above average at 114.4 (1.1). The most sensitive of the psychomotor tests for organic brain disease was the symbol digit coding (SDC) test (normal score 100, abnormal <85). Participants performed less well on this test (54.5 (6.0)) than expected from their pFSIQ (P<0.0001) and a little less poorly on the averaged less discriminating tests within the battery (86.1 (2.5), P<0.0001). In a comparison with the 15 sibling pairs (affected people's age 41.0 (3.3) years v sibling age of 42.7 (3.1) years (P=0.36) the exposed people had similar pFSIQ (114.7 (2.1)) to their siblings (116.3 (2.1), (P=0.59) but performed badly on the symbol digit coding test (51.8 (16.6)) v (87.5 (4.9) for siblings, P=0.03). The flash-pattern differences in exposed people were greater than in 42 unrelated control subjects of similar age (27.33 (1.64) ms v 18. 57 (1.47) ms, P=0.0002). The 15 unexposed siblings had significantly better flash-pattern differences than their affected siblings (13.4 (2.4) ms v 29.6 (2.9) ms, P=0.0002). No effect of anxiety could be shown on these measurements from the analysis of the anxiety scores of exposed people. CONCLUSION: People who were exposed to the contaminated water at Camelford suffered considerable damage to cerebral function, which was not related to anxiety. Follow up studies would be required to determine the longer term prognosis for affected individuals.

OBJECTIVES: To determine the effect of adding salmeterol 50 micrograms twice daily for six months to current treatment in subjects with asthma who control their inhaled corticosteroid dose according to a management plan. DESIGN: A double blind, randomised crossover study. SETTING: Nottingham. SUBJECTS: 101 subjects with mild or moderate asthma taking at least 200 micrograms twice daily of beclomethasone dipropionate or budesonide. INTERVENTIONS: Salmeterol 50 micrograms twice daily and placebo for six months each, with a one month washout. Subjects adjusted inhaled steroid dose according to guidelines. MAIN OUTCOME MEASURE: Reduction in inhaled steroid use, exacerbations of asthma, and use of oral steroids. RESULTS: Data were available for 87 subjects. When compared with placebo salmeterol treatment was associated with a 17% reduction in inhaled steroid use (95% confidence interval 12% to 22%) with no significant difference in the number of subjects who had an exacerbation (placebo 25%, salmeterol 16%) or use of oral steroids. For secondary end points salmeterol treatment was associated with higher morning and evening peak expiratory flow and forced expiratory volume in one second; a reduction in symptoms, bronchodilator use and airway responsiveness to methacholine; and no effect on serum potassium concentration, 24 hour heart rate, or the final forced expiratory volume in one second achieved during a salbutamol dose-response study. CONCLUSIONS: In subjects who adjusted their inhaled steroid treatment according to guidelines the addition of salmeterol 50 micrograms twice daily was associated with a reduction in inhaled steroid use and improved lung function and symptom control.

The present study builds on Hunter and Boster's model of compliance-gaining by adding conceptual and operational definitions of emotional response and by providing a theoretical framework for understanding relationships between emotional response and message selection. Specifically, Russell's (1978) and Mehrabian's (1980) three dimensional model of emotional response is offered to clarify the key concept—emotion. A measurement tool designed to tap the dimensions of pleasure, arousal, and dominance is used to test two hypotheses that seek to: (a) define the relative importance of the predicted emotional response of the selector and listener for compliance-gaining message selection: and (b) define the relative importance of each dimension of the selector's predicted emotional response on compliance-gaining selection. As predicted the selector's level of pleasure was most related to compliance-gaining selection.

To study the systemic and regional hemodynamic effects of the new antihypertensive agent pinacidil, the authors administered intravenously two doses of pinacidil (0.1 mg/kg) to patients with hypertension after 3 days of randomized, double‐blind pretreatment with either propranolol or placebo. Pinacidil administration decreased systemic arterial pressure and total peripheral vascular resistance in both groups of patients. It also decreased pulmonary artery wedge pressure, and increased cardiac output, heart rate, and plasma norepinephrine levels; the changes in cardiac output and heart rate were attenuated by propranolol pretreatment. In addition, propranolol‐pretreated patients responded to pinacidil with a decrease in forearm blood flow. In contrast, pinacidil administration exerted no significant effects on right atrial pressure, stroke volume, or mean pulmonary arterial pressure alone or in combination with propranolol. The results show that pinacidil is a potent arterial dilator but has little effect on the venomotor tone in patients with hypertension.

Counting the warsCount Alexandre de Marenches and David A. Andelman:The Fourth World War: Diplomacy and Espionage in the Age of Terrorism William Morrow, New York, 1992, 281 p., $23.00.The Israeli nuclear minimaxSeymour M. Hersh:The Samson Option: Israel's Nuclear Arsenal and American Foreign Policy Random House, New York, 1991, 356 p., $23.00.Weighing evidence for the intelligence analystDavid A. Schum:Evidence and Inference for the Intelligence Analyst 2 Vols./ University Press of America, 1987, Vol. 1 - 486 p., $125.00; Vol.2 - 359 p., $85.00.Yankee secretsEdmund R. Thompson, ed.:Spies of the American Revolution David Atlee Phillips New England Chapter, Association of Former Intelligence Officers, Kennebunk, Maine, 1991, 234 p., $12.95.Enquiring minds want to know…Peter Gudgin:Military Intelligence: The British Story Arms and Armour Press, London, 1989, 156 p., $21.95.

"Shootdown" shutdownR. W. Johnson:Shootdown: Flight 00 7 and the American Connection Viking, New York, 1986, 335p., $18.95.A history of secretsChristopher Andrew:Her Majesty's Secret Service: The Making of the British Intelligence Community. Viking, New York, 1986, 619 p., $25.00Draining the swimming poolRoger Faligot and Pascal Krop:La picine. Les services secrets français 1944-1984 Seuil Paris, 1985,431 p., FFr99.What price complacency?Wesley K. Wark:The Ultimate Enemy - British Intelligence and Nazi Germany, 1933-1939. Cornell University Press, Ithaca, N.Y., 1985, 303 p., $32.50The intelligence bureaucracyG. W. Hopple and B. W. Watson, eds.:The Military Intelligence Community Westview Press, Boulder, Colo., 1986, 300 p., $29.50.A new remembrance of things pastRear Admiral Edwin T. Layton, N.S.N. (Ret.), with Captain Roger Pineau, U.S.N.R. (Ret.), and John Dostello:And I Was There. William Morrow & Co., New York, 1985, 596 p., $19.95.DisinformationLadislav Bittman:The KGB and Soviet Disinformation: An Insider's View Pergamon-Brassey's International Defense Publishers, McLean, Va., 1985, 226 p., $16.95.Revisiting the "Rogue Elephant" cageJohn M. Oseth:Regulating U.S. Intelligence Operations The University Press of Kentucky, Lexington, Ky., 1985, 254 p., $24.00.Loch K. Johnson:A Season of Inquiry: The Senate Intelligence Investigation The University Press of Kentucky, Lexington, Ky., 1985, 328 p., $31.00.Spookspeak for real?Henry S. A. Becket:The Dictionary Of Espionage, Spookspeak into English Stein and Day, Inc., New York, 1986, 203 p., $17.95.A case man on his ownWilliam Hood:Spy Wednesday. Norton & Co., New York, 1986, 282 p., $14.95.

The P450 2A6 catalyzed 7-hydroxylation of coumarin proceeded with a mean Km of 0.40 (+/-0.13) microM and Vmax of 6.34 nmol/nmol P450/min (36-fold variation) in microsomal preparations from a panel of 12 human livers. Substrate depletion was avoided during the kinetic determinations. 8-Methoxypsoralen (8-MOP) is a potent mechanism-based inactivator of human liver P450 2A6 and reconstituted purified recombinant P450 2A6 based on the following evidence: 1) 8-MOP causes time, concentration, and NADPH-dependent loss of P450 2A6 activity that is not reversed by potassium ferricyanide or extensive dialysis, 2) loss of P450 2A6 activity is associated with a loss of spectrally observable P450, 3) addition of nucleophiles or reactive oxygen scavengers to the incubations does not prevent inactivation of P450 2A6, and 4) 8-MOP-dependent P450 2A6 inactivation is inhibited (concentration dependent) by the addition of a competitive inhibitor (pilocarpine). Inactivation is selective for P450 2A6 at low concentrations of 8-MOP (2.5 microM) after short incubation time periods (3 min) and was characterized by a KI of 0.8 and 1.9 microM in a reconstituted and microsomal system, respectively, and a kinact of 1 min-1 and 2 min-1 in a reconstituted and microsomal system, respectively. A substrate depletion partition ratio of 21 was calculated for the inactivation of recombinant P450 2A6. Potency and selectivity suggest that 8-MOP could be a useful tool in vitro for evaluating P450 2A6 activity in various enzyme preparations.

An analysis of 55 adult patients (age >15 yr) with previously untreated acute lymphoblastic leukemia (ALL) was undertaken to correlate presenting clinical features with outcome of treatment. Patients achieving complete remission (CR) were compared to those without CR for the presence or magnitude of 24 pretreatment characteristics. The effect of each characteristic on remission duration and survival was studied using the proportional hazards method. Younger age predicted longer remission duration and survival but was not related to attainment of CR. The L1 FAB subtype was more frequently associated with CR than was L2. It predicted longer remission duration and survival compared to L2, but when age was considered concurrently, the effect of FAB subtype was lost for remission duration and considerably diminished for survival. The absence of infection favored attainment of CR, and elevated serum creatinine had a negative effect on survival. Statistically less certain associations were marrow cellularity >90% and absence of weight loss favoring CR; female sex and lower neutrophils and hemoglobin favoring longer remission duration; and lower aspartate transaminase favoring longer survival. Total numbers of white cells, blasts or platelets, fever, purpura, organomegaly, lymphadenopathy, and other serum chemistries were not significantly related to outcome. For adults with ALL, these results both confirm and repudiate previously noted prognostic associations and demonstrate that many important prognostic indicators of childhood ALL do not apply to the adult disease.

The article reports on the birth of a beam documents, which is considered as the advent of a vital new technology in World War II Britain. As it was stated by Air Chief Marshal Hugh Dowding, commander in chief of Royal Air Force (RAF) Fighter Command, to the head of research at Fighter Command that the war will be won by science thoughtfully applied to operational requirements. His words summed up the essence of the RAF's victory in the Battle of Britain, but this aspect is often underplayed in accounts of World War II. Without an effective detection system, defending fighters would have had to spend long hours on standing patrols; which, with its limited resources, the RAF could ill-afford to do.

The skin lesions of erythema annulare centrifugum developed in a 58-year-old woman who had Hodgkin's disease. Response of the neoplasm to vinblastine sulfate was accompanied by disappearance of the skin lesions. When therapy was discontinued, both disorders recurred, and both responded to reinstitution of vinblastine therapy. To our knowledge, this case is the first reported association of erythema annulare centrifugum and Hodgkin's disease. The cutaneous manifestations in this patient were a nonneoplastic concomitant of her neoplastic disorder.(Arch Intern Med 139:486-487, 1979)

Peak compression phenomena are studied and applied to the analysis of lipid emulsion samples of clevidipine. Alcohols and water are found to generate system peaks on a silica column with 2-propanol-modified carbon dioxide. The retention times of the system peaks are found to vary as a function of type (water or alcohol) and chromatographic conditions (pressure, temperature, and modifier). By selecting an appropriate system peak generator and chromatographic conditions, the peak compression effect is created for the analysis of an emulsion sample of clevidipine solution containing water, methanol, and acetonitrile. The presence of buffer or lipids in the sample does not affect the peak compression phenomena.

The mechanism for the initiation of blood-brain barrier damage and intrathecal inflammation in patients infected with the human immunodeficiency virus (HIV) is poorly understood. We have recently reported that tumour necrosis factor-α (TNF-α) mediates active neural inflammation and blood-brain barrier damage in HIV-1 infection. Stimulation of endothelial cells by TNF-α induces the expression of intercellular adhesion molecule-1 (ICAM-1), which is an important early marker of immune activation and response. We report herein for the first time the detection of high levels of free circulating ICAM-1 in serum and cerebrospinal fluid of patients with HIV-1 infection. Free circulating ICAM-1 in these patients correlated with TNF-α concentrations and with the degree of blood-brain barrier damage and were detected predominantly in patients with neurologic involvement. These findings have important implications for the understanding and investigation of the intrathecal inflammatory response in HIV-1 infection.

The pathogenesis of brain inflammation and damage by human immunodeficiency virus (HIV) infection is unclear. Because blood–brain barrier damage and impaired cerebral perfusion are common features of HIV-1 infection, we evaluated the role of tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in mediating disruption of the blood–brain barrier. Levels of TNF-α were more elevated in cerebrospinal fluid (CSF) than in serum of HIV-1 infected patients and were mainly detected in those patients who had neurologic involvement. Intrathecal TNF-α levels correlated with signs of blood–brain barrier damage, manifested by high CSF to serum albumin quotient, and with the degree of barrier impairment. In contrast, intrathecal IL-1β levels did not correlate with blood-brain barrier damage in HIV-1 infected patients. TNF-α seems to be related to active neural inflammation and to blood–brain barrier damage. The proinflammatory effects of TNF-α in the nervous system are dissociated from those of IL-1β.

A high-performance liquid chromatograph-evaporative light scattering detector is modified and interfaced with a supercritical fluid chromatograph. The detector performance is evaluated by monitoring the response of several steroids. Specifically the effects of nitrogen makeup gas flow rate, carbon dioxide modifier type, modifier concentration, evaporative light scattering detector orifice size, and detector temperature are determined. As the nitrogen gas flow rate increases, the response of the analyte decreases, but the increased flow improves peak shape to mimic that obtained with ultraviolet detection. Furthermore, increasing the detector temperature causes the response of the analytes to decrease. A detection limit of 10 ng or less is determined for progesterone and testosterone with 2% and 20% (v/v) methanol-modified carbon dioxide on a Deltabond cyano column (4.6 mm × 15 cm, 5 μm) at 150 mL/min and 1000 mL/min decompressed carbon dioxide. The separations of polyethylene glycols and ginko biloba leaf extract with the optimized conditions are reported.

Several letters to the editor are presented in response to articles in previous issues, including "Britain's Gallantry Is Not Dead," by William L. Worden in the February 17, 1951 issue, "The Impostor," by Michael Fessier in the February 3, 1951 issue, and "The Rockefellers," by Joe Alex Morris in the December 30, 1951 issue.