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In a National Toxicology Program (NTP) chronic inhalation study with methyl isobutyl ketone (MIBK), increases in hepatocellular adenomas and hepatocellular adenomas and carcinomas (combined) were observed in male and female B6C3F

Background: Recently, a combination product (Daivobet® ointment: calcipotriol 50 µg/g, betamethasone dipropionate 0.5 mg/g) has been developed for the treatment of psoriasis. Objective: This study aimed to demonstrate that the atrophogenic potential of Daivobet is less or equal to the skin thinning produced by Diprosone® (betamethasone dipropionate 0.05 mg/g). Methods: The forearms of 45 subjects were treated with Daivobet and Diprosone or Daivobet and its vehicle twice daily over a 4-week period. Sonographic measurements for full skin thickness, clinical assessments and biopsies were carried out. Results: A confidence interval approach was used to establish that skin thinning following treatment with Daivobet was equal to or less than thinning with Diprosone. Histological results did not suggest differences between Daivobet and Diprosone. Clinical signs of atrophy or irritation were not observed. Conclusions: The atrophogenic potential of Daivobet and Diprosone was similar following twice daily application over a 4-week treatment period. Skin irritation was not observed.

The muon g-2 experiment at Brookhaven has successfully completed two exploratory runs using pion injection and direct muon injection for checkout and initial data taking. The main components of the experiment, which include the pion beam line, the superconducting storage ring and inflector magnets, the muon kicker and the lead-scintillating fiber calorimeters have been satisfactorily commissioned. First results on the anomalous magnetic moment of the positive muon from pion injection are in good agreement with previous experimental results for a(mu+) and a(mu-) from CERN and of comparable accuracy (13 ppm). Analysis of the 1998 muon injection run is in progress and expected to improve the precision to about 4 ppm. A first production run is scheduled for January 1999 with the goal of reaching the 1 ppm error level.

The muon anomalous magnetic moment has been measured in a new experiment at Brookhaven. Polarized muons were stored in a superferric ring, and the angular frequency difference, {omega}{sub a} , between the spin precession and orbital frequencies was determined by measuring the time distribution of high-energy decay positrons. The ratio R of {omega}{sub a} to the Larmor precession frequency of free protons, {omega}{sub p} , in the storage-ring magnetic field was measured. We find R=3.707thinsp220(48){times}10{sup {minus}3} . With {mu}{sub {mu}}/{mu}{sub p}=3.183thinsp 345thinsp47(47) this gives a{sub {mu}{sup +}}=1thinsp165thinsp 925(15){times}10{sup {minus}9} ({plus_minus}13 ppm ), in good agreement with the previous CERN measurements for {mu}{sup +} and {mu}{sup {minus}} and of approximately the same precision. {copyright} {ital 1999} {ital The American Physical Society}

The muon (g−2) experiment at Brookhaven has just completed a 3-month run for checkout and initial data-taking. In the first two months beam was taken in a parasitic mode where one out of ten AGS pulses was delivered for commissioning of the beam line, quadrupoles, detectors, and data acquisition system. This was followed by four weeks of dedicated data collection. The main components of the experiment, which include the pion/muon beam line, the superconducting inflector, the superferric storage ring with its pulsed electric quadrupoles and magnetic field measurement system, and the detector system based on lead-scintillating fiber electron calorimeters, have been satisfactorily commissioned. The muon (g−2) precession frequency is clearly seen as a large signal. It is estimaed that over 25×106 decay positrons with energies greater than 1.5 GeV have been detected.

Neutrophil adhesion and direct cytotoxicity for cardiac myocytes require chemotactic stimulation and are dependent upon CD18-ICAM-1 binding. To characterize the potential role of IL-8 in this interaction, canine IL-8 cDNA was cloned and the mature recombinant protein expressed in Escherichia coli BL21 cells. Recombinant canine IL-8 markedly increased adhesion of neutrophils to isolated canine cardiac myocytes. This adhesion resulted in direct cytotoxicity for cardiac myocytes. Both processes were specifically blocked by antibodies directed against CD18 and IL-8. In vivo, after 1 h of coronary occlusion, IL-8 mRNA was markedly and consistently induced in reperfused segments of myocardium. IL-8 mRNA was not induced in control (normally perfused) myocardial segments. Minimal amounts of IL-8 mRNA were detected after 3 or 4 h of ischemia without reperfusion. Highest levels of induction were evident in the most ischemic myocardial segments. IL-8 mRNA peaked in the first 3 h of reperfusion and persisted at high levels beyond 24 h. IL-8 staining was present in the inflammatory infiltrate near the border between necrotic and viable myocardium, as well as in small veins in the same area. These findings provide the first direct evidence for regulation of IL-8 in ischemic and reperfused canine myocardium and support the hypothesis that IL-8 participates in neutrophil-mediated myocardial injury.

The mechanism by which tumour cells may be killed in vitro by exogenous polyunsaturated fatty acids may involve lipid peroxidation. Gamma-linolenic acid caused a dose and time-dependent reduction in ZR-75-1 cell growth. However, altering either the incubator temperature (35, 37 and 39 degrees C) or the oxygen content (16, 21 and 26%) had little effect on either the growth of cells in the presence of gamma-linolenic acid or on thiobarbiturate reactive material levels over a 7 day period. Thus, small changes in cell culture conditions do not affect 18:3n-6 cytotoxicity or markers of lipid peroxidation.

Whiskey produced in illegal stills (ie, "moonshine") remains an important and underappreciated source of lead toxicity in some rural counties of the Southeast. From March 5 through October 26, 1991, eight adult patients with elevated blood lead levels were identified at a rural county hospital in Alabama and were reported to the Alabama Department of Public Health notifiable disease surveillance system. A case-patient was defined as any person 17 years of age or more who presented to the hospital from January 1, 1990, through December 31, 1991, and had a blood lead level of 0.72 mumol/L or more (15 micrograms/dL or more). To identify cases and potential sources of lead exposure, we reviewed medical and laboratory records from the hospital, interviewed patients with elevated blood lead levels, and determined the lead content of moonshine samples. Nine patients met the case definition, including one patient who was not reported to the state. Patients ranged in age from 28 to 62 years; blood lead values ranged from 0.77 to 12.50 mumol/L (16 to 259 micrograms/dL). The most frequent signs of possible lead toxicity included seizures (six), microcytic anemia (five), and encephalopathy (two); one patient died. The only identified source of lead exposure for the nine patients was moonshine ingestion. Moonshine samples available from local stills contained sufficient amounts of lead (340 to 4600 mumol/L) to result in the observed blood lead levels. This investigation emphasizes the adverse health effects and ongoing public health impact of moonshine ingestion.

We have developed a method for measuring the improvement in lithography produced using proximity correction. We have used this method to characterize the performance of the Cambridge Instruments proximity correction software. The goal of this work is to explore the parameter space of the correction. We have used our measurement technique to show quantitatively the effect on lithographic performance of: scattering fit model (double Gaussian, triple Gaussian, and double Gaussian plus exponential), variation in scattering coefficients, and variation of computation parameters (integration grid size). For our study, we have used a common e‐beam process: 0.5 μm thick PMMA resist on silicon, with a 20 KeV, 75 nm Gaussian beam. We have studied several geometries with dimensions as small as 0.2 μm. We have found that feature sizes of the proximity corrected exposures are quite insensitive to large variations in input parameters. Variation of the double gaussian parameters alpha and eta of ±30% from their best‐fit value produced

Newborn Holstein bull calves were fed either analytical pentachlorophenol (aPCP) or technical pentachlorophenol (tPCP) for 6 wk to establish and compare the clinical and pathologic manifestations of toxicity. Four groups of three calves/group were each fed either 1 or 10 mg X (kg body weight)-1 X d-1 of either aPCP or tPCP. A fifth group served as control. Dosages of both PCP preparations were normalized to contain equal concentrations of PCP. Toxic effects were observed only at the 10 mg/kg dose in the tPCP-treated calves. These effects included decreased body weight gain, anorexia, decreased serum protein concentration, elevated serum gamma glutamyl transferase, and decreased triiodothyronine (T3) and thyroxine (T4) concentrations. Histologic lesions included cortical atrophy in the thymus and squamous metaplasia and hyperkeratous changes in the Meibomian gland of the eyelid. Thyroid function, which was assessed in vivo by measuring the rate of T3 and T4 production over 4 h after thyrotropin-releasing hormone (TRH)-challenge, was not impaired suggesting an extrathyroidal site of toxic action. Although serum chemistry indicators were suggestive of hepatic injury there were no discernable lesions. Organ weight analyses were inconclusive but there was a tendency toward enlargement of liver, kidneys and thyroid and decreased weight of lungs, spleen and thymus. A toxic effect clearly related to PCP and not its contaminants was depressed active transport of p-aminohippurate measured in kidney slices in vitro. Steady state concentrations of PCP in serum were about 40 and 90 ppm for the 1 and 10 mg/kg groups, respectively. Concentrations of PCP among the major organs were comparable.

A throe dimensional variable dimensioned computer model of a man has been developed which can be used as a conversational mode design tool. This paper illustrates the use of this model for equipment design, in particular to determine whether controls can be reached and whether equipment dimensions are suitable to match different members of the population. The equipment may be described cither by special purpose or general purpose environmental modelling systems. The modules of the general purpose system may be assembled into a model of the equipment and then evaluated by taking the operator, represented by the computer man, through a typical work sequence. If the dimensions or positions of the modules are unsatisfactory they may be altered conversationally and the new design retested.

Summary: The incidence of rapid labour at Mill Road Maternity Hospital, Liverpool, increased between 1967 and 1971 due to active management of labour and more frequent induction of labour. The results of the present study of 722 patients indicate that provided rapid labour (whether induced or spontaneous) takes place under close supervision, there is no disadvantage to mother or fetus.

Liquid scintillation counting solutions for radioimmunoassay of hepatitis associated antigen (HBsAg) are evaluated and discussed. Data are also presented which indicates that liquid scintillation counting could be carried out by placing cut-off Ausria-125 test tubes in counting vials containing 10 ml of either Brays, Unogel, or Instagel solutions. The data suggest that Brays was the least effective and Unogel and Instagel were the most effective liquid scintillation counting solutions. This is a fundamental consideration if a laboratory is contemplating an initial investment in counting equipment. The acquisition of a liquid scintillation counter provides additional capabilities for the clinical laboratory interested in radioisotope measurements. In addition, if a laboratory already has a liquid scintillation counter (Beta counter), the director of the clinical laboratory may elect not to purchase additional counting equipment (gamma counter) since he already has the added advantage of measuring iodine-125 with the Beta counter. The authors propose liquid scintillation (RIA) as an alternative counting system for HBsAg detection in hospital patients and donors.

A modified microneutralization test for influenza A and B and parainfluenza 1 and 2 viruses was developed. Use of continuous cell lines (Madin-Darby canine kidney and LLC-MK2), hemagglutination for virus detection, and transfer plates and other microtiter equipment resulted in a highly mechanized technique suitable for titrating large numbers of sera easily and relatively inexpensively. Titers of heat-inactivated human sera were enhanced 0.5 to 3.5 log2 by addition of fresh hamster or human serum to the test. Seroconversion rates and identification of seronegative persons were not changed by fresh serum enhancement, but the magnitude of seroconversion was often increased and the distribution of positive titers was broadened. For influenza A and B, seroconversion rates in the microneutralization test were equivalent to those obtained in rhesus monkey kidney tube neutralization tests. For influenza B, seroconversion rates by micro-neutralization were almost double those obtained with the hemagglutination inhibition test, but the rates were similar for influenza A/USSR (H1N1). Preexisting microneutralization titers correlated well with resistance of infection with influenza B. Limited experience with parainfluenza 1 and 2 was similar to previously reported findings with the tube neutralization test.

Cardiac lymph from a canine model of myocardial ischemia and reperfusion was examined for evidence of chemotactic activity. Lymph was continuously collected from awake animals before and during a 60-minute coronary artery occlusion and up to 6 hours after the initiation of reperfusion. It was assessed for the ability to activate the following proinflammatory functions in neutrophils isolated from the blood of healthy dogs: 1) morphological changes characteristic of chemotactic stimulation, which were assessed by phase contrast microscopy, 2) orientation of canine neutrophils in a gradient of cardiac lymph, which was assessed in Zigmond chambers, 3) the binding of monoclonal antibodies reactive with CD11b and CD18 adherence glycoproteins, which was assessed by flow cytometry, and 4) adherence of canine neutrophils to monolayers of canine jugular vein endothelium, which was assessed in vitro by a visual assay. Lymph samples collected after 1 hour of reperfusion in animals demonstrating ECG evidence of ischemia and histological evidence of infarction exhibited significant stimulatory activity for each of the functions tested. Shape change-inducing activity was evaluated at more frequent intervals than other functions and was found to peak at 1 hour after initiation of reperfusion and to disappear by 6 hours. In addition, the CD11b/CD18 levels on neutrophils isolated from cardiac lymph collected during reperfusion were significantly greater than neutrophils obtained before or during occlusion. Animals that failed to exhibit evidence of infarction also failed to exhibit increased stimulatory activity in lymph collected during reperfusion, and surface levels of CD11b/CD18 on neutrophils collected from reperfusion lymph were not elevated. This study provides direct evidence supporting the hypothesis that chemotactic activity is generated in ischemic and reperfused myocardium.

The humoral and cellular contributions to PMN motility in vitro were studied in 37 malnourished (PCM) pediatric patients. Early-phase directed migration to BCF and to ZANS was diminished significantly (p less than 0.001) in severe PCM patients as compared to healthy adult or age-matched controls or respective nutritionally restored patients. Abnormalities were reversible after nutritional restoration and unrelated to occurrence of clinical infection. To determine the pathogenic mechanism of impaired PMN mobility in PCM, studies of cell morphology and adhesive function were performed. Abnormalities observed in severe PCM suspensions included significantly (p less than 0.001) increased baseline (unstimulated) adherence values and impaired CF modulation of adhesive function. Diminished enhancement of PMN adherence or decreased (relative to baseline) adherence values were observed in response to BCF (mean % delta = +5) or f-Met-Leu-Phe (mean % delta = -6) as compared to adult PMN values of +28% delta and +31% delta, respectively. That these abnormalities may result from in vivo CF prestimulation was suggested by findings of "activated" PMN morphology in suspensions prior to in vitro stimulation, and abnormalities of the distribution of PMN surface adhesion sites under conditions of chemotactic stimulation. Further investigations will be required to determine the underlying pathogenic mechanism(s) accounting for our observations.

The SAMMIE computer-aided workplace and work task design system is intended to facilitate the consideration of human factors within the design process from the conceptual, pre-mock-up stage of design onwards. The software consists of six main parts: a computerized man-model, a workplace modelling system, a language with which to describe the work tasks to be performed in that workplace, heuristic rules for workplace layouts, various measures of effectiveness which can aid the assessment of the suitability of the workplace, and finally a system for interactive man-machine communication. The workspace model and the model of the operator are displayed on a screen of an interactive graphics terminal and the workspace is then evaluated for an operator performing specified tasks. The dimensions and arrangements of the workspace, the dimensions of the operator, and to a lesser extent the work task may all be interactively changed, and the proposed design then reevaluated. Measures of effectiveness include reach, checks on visual suitability, and an evaluation of the methods and times required to perform the task. These, and other measures, may be used by the computer itself, and interactively under the designer's control.

Myocardial infarction is a rare complication of pregnancy, only 45 proven cases having been reported. In only one patient was rheumatic heart disease an associated factor (Goldberger and Pokress, 1950).

We compare and discuss three electrophoretic methods for identifying hemoglobins S, A, C, F, and D or G. Electrophoresis on citrate agar gel was more sensitive than electrophoresis on cellulose acetate for detecting hemoglobins S and F, a fundamental consideration in designing cord-blood screening programs for detecting hemoglobin S carriers. Electrophoresis on starch gel is evidently an acceptable method for subtyping hemoglobins AA, CC, AS, SS, AC, and SC, and is more sensitive than cellulose acetate for identifying hemoglobin A1A2. Costs for the citrate agar gel, cellulose acetate, and starch gel procedures are presented.

The records of 15 dogs diagnosed as having juvenile cellulitis (juvenile pyoderma, puppy strangles) were evaluated for clinical, laboratory, and therapeutic results. Mandibular lymphadenopathy was observed in 14 dogs, and was not associated with skin lesions in 5 dogs. Edema, pustules, papules, or crusts were noticed periorally, periocularly, on the chin or muzzle, or in the ears of those dogs with skin lesions. Eight dogs were lethargic; fever and anorexia were inconsistent findings. Four dogs had signs of pain on manipulation of their joints. Complete blood counts revealed leukocytosis with neutrophilia in 4 dogs, and normocytic, normochromic anemia in 6 dogs. Three dogs had suppurative lymphadenitis with many neutrophils. Cytology of the aspirate of pustules or abscesses in 6 dogs revealed many neutrophils without bacteria. Coagulase-positive Staphylococcus spp were isolated from draining lesions in 2 dogs. Intact abscesses and lymph nodes were negative for bacterial growth in 4 dogs. Three of these dogs were being administered antibiotics at the time of bacterial culturing. Cytology of the aspirates of joints in 3 of the 4 dogs with joint pain revealed suppurative arthritis with no bacteria, and the aspirates were negative for bacterial growth on culturing, although all 3 dogs were being administered antibiotics at the time of culturing. Of 12 dogs initially treated with antibiotics, only 4 (33%) responded favorably; the other 8 dogs were then given antibiotics and corticosteroids. Three dogs were initially given antibiotics and corticosteroids. All dogs treated concurrently with antibiotics and corticosteroids responded favorably. One of these dogs had a relapse after treatment was discontinued. The concurrent arthritis in 4 of the dogs resolved with treatment of the juvenile cellulitis and did not redevelop once the medication was discontinued. Concurrent treatment with antibiotics (cephalosporins) and prednisone (2.2 mg/kg of body weight/day) was the most consistently effective treatment in the dogs in this study.

Histologic examination was used to determine the anatomic organization of the feline bulbospongiosus muscle (BSM). Bilaterally symmetrical cranial, middle, and caudal muscle fiber groups were identified. The caudal group was the largest of the 3 groups. Mean cross-sectional diameter of nonfixed BSM fibers was 79 micron. Muscle spindles were not observed in serial histologic sections. The innervation of the BSM was provided by the deep perineal nerve. Contractile properties of the BSM were determined in vitro, using direct muscle stimulation. Mean time-to-peak tension values were 71.4 ms and 62.7 ms at 30 C and 37 C, respectively, and were longer than that for the feline periurethral striated muscle and external anal sphincter muscle, but slightly shorter than that for the slow-twitch soleus muscle. Stimulation frequency at peak tetanic tension was 40 Hz, twitch-to-tetanus ratio was 0.30, and stimulus interval at peak tension for double response was 44 ms. Electrophysiologic properties examined were resting potentials and miniature end-plate potentials (MEPP). Mean resting potential was 68 mV. The MEPP had low mean amplitude (0.57 mV), fast mean rise time (0.99 ms), and low maximal frequency (0.06 Hz). Only focally recordable MEPP were observed. Pharmacologic properties were investigated by alternating direct and indirect stimulation. The latter was accomplished by electric field stimulation of intramuscular nerve fibers. A high sensitivity of the BSM to d-tubocurarine blockade was present. The results of this study support classification of the BSM as a slow-twitch muscle.

A monoclonal antibody (MoAb), 273-34A, specifically binds to an epitope expressed almost exclusively on capillary endothelial cells of the lung. Within 15 min after i.v. injection, approximately 80 to 85% of the injected radioiodinated MoAb 273-34A accumulates in the lung. Approximately 90 to 95% of the recovered dose is found in the lung for up to 1 week postinjection. Ratios of MoAb 273-34A to a nonspecific, irrelevant MoAb 135-14 are 250 to 285 times higher in the lung than in the serum. When 273-34A was coupled with palmitic acid and incorporated into liposomes, the amount of 125I-labeled liposomes recovered per g of tissue was 12 times higher in the lung than in the liver at 15 min postinjection, and 22 times higher at 5 h postinjection. At 24 h postinjection the amount of liposomes per gram of lung tissue was still 6.0 times the amount per gram of liver tissue. Liposomes conjugated to MoAb 273-34A locate in the lung 20 and 15 times better than do liposomes conjugated to the nonspecific MoAb 135-14 at 15 min and 24 h postinjection, respectively. The results indicate that this immunoliposome system could be used as a model for enhanced drug delivery to the lung. The potential use for delivering anticancer drugs for therapy of lung tumors is discussed.

We report on the fabrication of a chirped, phase mask that was used to create a fiber Bragg grating (FBG) device for the compensation of chromatic dispersion in longhaul optical transmission networks. Electron beam lithography was used to expose the grating onto a resist-coated quartz plate. After etching, this phase mask was used to holographically expose an index grating into the fiber core [K. O. Hill, F. Bilodeau, D. C. Johnson, and J. Albert, Appl. Phys. Lett. 62, 1035 (1993)]. The linear increase in the grating period, “chirp,” is only 0.55 nm over the 10 cm grating. This is too small to be defined by computer aided design and a digital deflection system. Instead, the chirp was incorporated by repeatedly rescaling the analog electronics used for field size calibration. Special attention must be paid to minimize any field stitching and exposure artifacts. This was done by using overlapping fields in a “voting” method. As a result, each grating line is exposed by the accumulation of three overlapping ...