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Morphologists have historically had to rely on destructive procedures to visualize the three‐dimensional (3‐D) anatomy of animals. More recently, however, non‐destructive techniques have come to the forefront. These include X‐ray computed tomography (CT), which has been used most commonly to examine the mineralized, hard‐tissue anatomy of living and fossil metazoans. One relatively new and potentially transformative aspect of current CT‐based research is the use of chemical agents to render visible, and differentiate between, soft‐tissue structures in X‐ray images. Specifically, iodine has emerged as one of the most widely used of these contrast agents among animal morphologists due to its ease of handling, cost effectiveness, and differential affinities for major types of soft tissues. The rapid adoption of iodine‐based contrast agents has resulted in a proliferation of distinct specimen preparations and scanning parameter choices, as well as an increasing variety of imaging hardware and software preferences. Here we provide a critical review of the recent contributions to iodine‐based, contrast‐enhanced CT research to enable researchers just beginning to employ contrast enhancement to make sense of this complex new landscape of methodologies. We provide a detailed summary of recent case studies, assess factors that govern success at each step of the specimen storage, preparation, and imaging processes, and make recommendations for standardizing both techniques and reporting practices. Finally, we discuss potential cutting‐edge applications of diffusible iodine‐based contrast‐enhanced computed tomography (diceCT) and the issues that must still be overcome to facilitate the broader adoption of diceCT going forward.

NOTE from the Editor: Nursing Administration Quarterly does not normally publish literature searches. However, for our Informatics Column this quarter, we are sharing an overview of the sixth annual American Medical Informatics Association Nursing Informatics Working Group's (AMIA-NIWG) review o

Purpose Video-assisted thoracoscopic surgery (VATS) lobectomy has become an accepted procedure for the treatment of selected cases of lung cancer. The aim of this project was to establish national practical recommendations for the management of patients suitable for VATS lobectomy. Methods The Scientific Committee of the VATS Lobectomy Group (a branch of the Italian Society of Thoracic Surgery) identified the consensus conference as an appropriate tool for a national debate. The consensus conference was organized following indications of the Italian Department of Health: a panel of experts reviewed the literature, the jury board revised the experts’ reports, and the national conference discussed and voted on statements. The strength of recommendation for a statement was classified as weak, fair, or high when the total score ranged between 51% and 67%, 68% and 84%, or 85% and 100%, respectively. Results Eighty-six Italian thoracic surgeons attended the 1st Italian Consensus Conference on VATS lobectomy in Giulianova, Italy, on October 29-30, 2015. Thirty-three topics were discussed: indications, surgical strategy, perioperative management, and training were the main topics. Consensus was reached on 24 statements that were consequently recommended. Conclusions The Italian Consensus Conference is the first attempt to discuss VATS lobectomy-related issues in a national scientific community. Such experience determined an improvement in epistemic knowledge among the Italian thoracic surgeons and could be a suggestion for other national communities.

Forensic taphonomy is an essential research field; however, the decomposition of human cadavers at forensic science facilities may lead to nutrient loading and the introduction of unique biological compounds to adjacent areas. The infrastructure of a water retention sys- tem may provide a mechanism for the biogeochemical processing and retention of nutrients and compounds, ensuring the control of runoff from forensic facilities. This work provides a proof of concept for a hydrologic retention system and an autonomous water quality monitoring pro- gram designed to mitigate runoff from The Southeast Texas Applied Forensic Science (STAFS) Facility. Water samples collected along a sam- ple transect were analyzed for total phosphorous, total nitrogen, NO 3 ,N O 2 ,N H4 ,F , and Cl. Preliminary water quality analyses confirm the overall effectiveness of the water retention system. These results are discussed with relation to how this infrastructure can be expanded upon to monitor additional, more novel, byproducts of forensic science research facilities.

“The additional potential (beyond the thermodynamic requirement) needed to drive a reaction at a certain rate is called the overpotential.”1 Over the last decade there has been considerable interest in the design and testing of molecular electrocatalysis for the interconversion of renewable energy and chemical fuels.2-5 One of the primary motivations for such research is the replacement of expensive and rare precious metal catalysts, such as platinum, with cheaper, more abundant metals.2,6-8 To become competitive with current electrocatalytic energy conversion technologies, new catalysts must be robust, fast, and energy-efficient. This last feature, the energy-efficiency, is dependent upon the overpotential. For molecular catalysts, the determination and reporting of overpotentials can be complicated by the frequent dependence on assumptions, especially when working in nonaqueous solvents. As overpotentials become lower, the meaningful comparison of molecular catalysts will require improved accuracy and precision. The intended purpose of this viewpoint is to provide a clear and concise description of overpotential and recommendation for its determination in molecular electrocatalysis. This material is based upon work supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the US Department of Energy, Office of Science, Office of Basic Energy Sciences.

Goals of this study were to: (1) develop distributional maps of modern rodent genera throughout the countries of South Africa, Lesotho, and Swaziland by georeferencing museum specimens; (2) assess habitat preferences for genera by cross-referencing locality position with South African vegetation; and (3) identify mean annual precipitation and temperature range where the genera are located. Conterminous South Africa including the countries of Lesotho and Swaziland Digital databases of rodent museum specimens housed in the Ditsong National Museum of Natural History, South Africa (DM), and the Division of Mammals, National Museum of Natural History, Smithsonian Institution, United States (NMNH), were acquired and then sorted into a subset of specimens with associated coordinate data. The coordinate data were then used to develop distributional maps for the rodent genera present within the study area. Percent habitat occupation and descriptive statistics for six climatic variables were then determined for each genus by cross-referencing locality positions with vegetation and climatic maps. This report presents a series of maps illustrating the distribution of 35 rodent genera based on 19,471 geo-referenced specimens obtained from two major collections. Inferred habitat use by taxon is provided for both locality and specimen percent occurrence at three hierarchical habitat levels: biome, bioregion, and vegetation unit. Descriptive statistics for six climatic variables are also provided for each genus based on locality and specimen percent incidence. As rodent faunas are commonly used in paleoenvironmental reconstructions, an accurate assessment of rodent environmental tolerance ranges is necessary before confidence can be placed in an actualistic model. While the data presented here represent only a subset of the modern geographic distributions for many of the taxa examined, a wide range of environmental regimes are observed, suggesting that more research is necessary in order to accurately reconstruct an environmental signature when these taxa are found in the fossil record.

Sustainable, carbon-neutral energy is needed to supplant the worldwide reliance on fossil fuels in order to address the persistent problem of increasing emissions of CO2. Solar and wind energy are intermittent, highlighting the need to develop energy storage on a huge scale. Electrocatalysts provide a way to convert between electrical energy generated by renewable energy sources and chemical energy in the form of chemical bonds. Oxidation of hydrogen to give two electrons and two protons is carried out in fuel cells, but the typical catalyst is platinum, a precious metal of low earth abundance and high cost. In nature, hydrogenases based on iron or iron/nickel reversibly oxidize hydrogen with remarkable efficiencies and rates. Functional models of these enzymes have been synthesized with the goal of achieving electrocatalytic H2 oxidation using inexpensive, earth-abundant metals along with a key feature identified in the [FeFe]-hydrogenase: an amine base positioned near the metal. The diphosphine ligands P(R)2N(R')2 (1,5-diaza-3,7-diphosphacyclooctane with alkyl or aryl groups on the P and N atoms) are used as ligands in Ni, Fe, and Mn complexes. The pendant amines facilitate binding and heterolytic cleavage of H2, placing the hydride on the metal and the proton on the amine. The pendant amines also serve as proton relays, accelerating intramolecular and intermolecular proton transfers. Electrochemical oxidations and deprotonations by an exogeneous amine base lead to catalytic cycles for oxidation of H2 (1 atm) at room temperature for catalysts derived from [Ni(P(Cy)2N(R')2)2](2+), Cp(C6F5)Fe(P(tBu)2N(Bn)2)H, and MnH(P(Ph)2N(Bn)2)(bppm)(CO) [bppm = (PAr(F)2)2CH2]. In the oxidation of H2 catalyzed by [Ni(P(Cy)2N(R')2)2](2+), the initial product observed experimentally is a Ni(0) complex in which two of the pendant amines are protonated. Two different pathways can occur from this intermediate; deprotonation followed by oxidation occurs with a lower overpotential than the alternate pathway involving oxidation followed by deprotonation. The Mn cation [Mn(P(Ph)2N(Bn)2)(bppm)(CO)](+) mediates the rapid (10(4) s(-1) at -95 °C), reversible heterolytic cleavage of H2. Obtaining the optimal benefit of pendant amines incorporated into the ligand requires that the pendant amine be properly positioned to interact with a M-H or M(H2) bond. In addition, ligands are ideally selected such that the hydride-acceptor ability of the metal and the basicity of a pendant are tuned to give low barriers for heterolytic cleavage of the H-H bond and subsequent proton transfer reactions. Using these principles allows the rational design of electrocatalysts for H2 oxidation using earth-abundant metals.

To convert solar energy into viable fuels, coupling light-harvesting materials to catalysts is a crucial challenge. Now, the combination of an organic supramolecular hydrogel and a non-precious metal catalyst has been demonstrated to be effective for photocatalytic H2 production.

Despite therapy with diuretics, digoxin, and angiotensin-converting enzyme inhibitors, congestive heart failure remains an important health problem with high mortality, and it is clear that new treatments for heart failure are needed. Evidence from basic research, animal studies, and clinical human trials indicates that high adrenergic tone in patients with heart failure is deleterious; furthermore, the deleterious effects are partially reversible with beta-adrenergic blockade. This article reviews the recent developments in our understanding of the pathophysiology of heart failure and the recent data concerning the treatment of heart failure with beta-blocking agents.

Ursodeoxycholic acid (UDCA) and methotrexate (MTX) have both been proposed as treatments for patients with primary biliary cirrhosis (PBC). It has been suggested that a combination of the two drugs may offer advantages over either used separately. In this pilot study, we sought to evaluate the safety and efficacy of this combination for patients with PBC. Thirty-two patients with antimitochondrial antibody positive PBC were prospectively entered into a pilot study and received UDCA, 13 to 15 mg/kg/d, in conjunction with MTX, 0.25 mg/kg/wk, for a period of 2 years. The results of this treatment were compared with those obtained from 180 patients with PBC studied in a placebo-controlled trial of UDCA alone conducted during the same period. Patients in the pilot study and randomized study were comparable with regard to age, gender, and liver biochemistries. The UDCA/MTX-treated patients were of earlier histologic stage and had a lower mean Mayo risk score. During this period, seven patients in the UDCA/MTX group were withdrawn, four for pulmonary toxicity (two who required hospitalization), and one each with mouth ulcer, extreme fatigue, and hair loss. The use of UDCA/MTX was not associated with improvement in symptoms. In the patients receiving UDCA/MTX, biochemical changes were comparable to those of patients receiving UDCA alone but superior to those in the placebo group (P < .05). Histological changes were comparable in all groups at 2 years. Cessation of MTX while UDCA was continued led to no deterioration in liver biochemistries.(ABSTRACT TRUNCATED AT 250 WORDS)

A case-control analysis of cancer registry data was used to examine the hypothesis that occupational exposure to sunlight influences the risk of melanoma. Occupation at diagnosis was available for 3,527 cutaneous melanomas and 53,129 other cancers identified by the Los Angeles County (California, United States) Cancer Surveillance Program among non-Spanish-surnamed White males aged 20 to 65 years between 1972 and 1990. Occupational exposure to sunlight was assessed by blinded expert coding of job titles as indoor, outdoor, and mixed indoor/outdoor. Relative to indoor occupations, proportionate odds ratios (OR) adjusted for age, level of education, and birthplace were 1.16 (95 percent confidence interval [CI] = 1.07-1.27) for indoor/outdoor occupations and 1.15 (CI = 0.94-1.40) for outdoor occupations. However, increasing levels of the education or training required for the occupation was associated more strongly with increased melanoma occurrence (ORs adjusted for age, occupational sun exposure, and birthplace, were 1.0, 1.63, 2.09, 2.23, and 2.99 for low-skill occupation, high school, college, postgraduate, and doctoral levels, respectively). Analysis of melanoma occurrence by job titles confirmed a clear variation by the required education or training level but not by the category of occupational sunlight exposure. The findings suggest that lifestyle factors associated with higher levels of education may be more important determinants of melanoma risk than characteristics of the work environment.

Preview Since the discovery of Helicobacter pylori 10 years ago, its role in peptic ulcer disease has been recognized. Now the questions are, What is the best way to eradicate the organism, and which patients should receive treatment? Dr Anderson explores the issues concerning H pylori infection in patients with recurrent ulcers and describes the most reliable treatment regimens available.

External root resorption is a frequent iatrogenic consequence of orthodontic treatment, particularly in the maxillary anterior teeth. Since resorption also occurs is a normal function of aging and since altered behaviors such as bruxism and chronic nailbiting accelerate resorption even in the absence of treatment, it was hypothesized that the long-term orthopedic forces of tongue thrusting leading to anterior open bites would also enhance the rates of clastic activity. In a series of 32 adolescents with open bites, the roots of permanent maxillary central incisors were significantly shorter and exhibited higher modal grades of periapical resorption than a matched series with deep bites before treatment. The open bite group also had less facial bony support for these teeth. Both series experienced discernible resorption during full-banded treatment but to comparable extents so that, after active treatment, the open bite series continued to possess significantly greater degrees of resorption. Consequently, the oral forces leading to apertognathia are themselves destructive of root integrity and merit early recognition and interception.

We tested the safety and efficacy of sibutramine, 5 and 20 mg, and placebo on weight loss. Medication was added to caloric restriction, behavior modification, and exercise in a parallel-group, double-blind clinical trial. Participants were 130% to 180% of ideal body weight and in good health. The study lasted 12 weeks over Thanksgiving, Christmas, and New Year's Day. Weight loss during 8 weeks of study medication was: placebo, 1.4 ± 2.1 kg (n = 19); 5 mg sibutramine, 2.9 ± 2.3 kg (n = 18); and 20 mg sibutramine, 5.0 ± 2.7 kg (n = 18) (p < 0.05 sibutramine, 5 and 20 mg, versus placebo; p < 0.05 sibutramine, 20 mg versus 5 mg). There is a significant dose-effect relationship. Five participants left the study before completion, all because of adverse events: placebo (one patient), 5 mg sibutramine (one patient), and 20 mg sibutramine (three patients). Sleep difficulties were noted by eight participants (20 mg sibutramine, seven patients; 5 mg, one patient; and placebo, no patients). Six of 21 participants receiving 20 mg complained of irritability, unusual impatience, or “excitation.” Sibutramine, 5 and 20 mg, added to a multimodal program assisted participants in losing weight. Clinical Pharmacology and Therapeutics (1991) 50, 330–337; doi:10.1038/clpt.1991.144

Ninety-two children with juvenile rheumatoid arthritis were randomly assigned to treatment in a multicenter, double-blind, 12-week trial designed to compare the efficacy and safety of a liquid formulation of ibuprofen at a dosage of 30 to 40 mg/kg/day versus those of aspirin at a dosage of 60 to 80 mg/kg/day. No significant intergroup differences in response rates or in the amount of improvement in articular indexes of disease activity were observed. More children treated with aspirin discontinued treatment early because of adverse reactions. After this trial, 84 additional patients with juvenile rheumatoid arthritis entered a 24-week, multidose (30, 40, and 50 mg/kg/day), open trial of ibuprofen suspension. Favorable response rates for the three groups were similar, and continued improvement was observed throughout the 24-week period. A dose-response relationship was observed with respect to adverse reactions of the upper gastrointestinal tract. We conclude that ibuprofen suspension is an effective nonsteroidal antlinflammatory drug and that its tolerability in children is acceptable.

The Multiband Imaging Photometer for Spitzer (MIPS) provides long wavelength capability for the mission, in imaging bands at 24, 70, and 160 microns and measurements of spectral energy distributions between 52 and 100 microns at a spectral resolution of about 7%. By using true detector arrays in each band, it provides both critical sampling of the Spitzer point spread function and relatively large imaging fields of view, allowing for substantial advances in sensitivity, angular resolution, and efficiency of areal coverage compared with previous space far-infrared capabilities. The Si:As BIB 24 micron array has excellent photometric properties, and measurements with rms relative errors of 1% or better can be obtained. The two longer wavelength arrays use Ge:Ga detectors with poor photometric stability. However, the use of 1.) a scan mirror to modulate the signals rapidly on these arrays, 2.) a system of on-board stimulators used for a relative calibration approximately every two minutes, and 3.) specialized reduction software result in good photometry with these arrays also, with rms relative errors of less than 10%.

Hepatic steatosis is a recognized feature of hepatitis C viral infection, particularly in genotype 3. The demographics and the associations contributing to moderate to severe steatosis in genotype 3 are not very well studied. The aim of this study is to determine the demographics and association of steatosis with fibrosis, obesity, diabetes, lipid levels, and risk factors among patients with hepatitis C virus (HCV) genotype 3. Two hundred ninety-three consecutive HCV patients (genotype 1, n = 218; genotype 2, n = 43; genotype 3, n = 32) at our institution were studied retrospectively. Demographic information such as height, weight, genotype, risk factors, serum cholesterol and triglyceride, and liver biopsy was collected. Steatosis was graded using the Brunt classification. HCV genotype 3-infected patients were younger (P < 0.04) and had lower serum cholesterol levels (P < 0.02) compared to nongenotype 3 patients. Moderate to severe steatosis was more prevalent in HCV genotype 3 patients (P < 0.001) with intravenous drug abuse as a risk factor (P = 0.04). Genotype 3 was the independent predictor of steatosis in all patients. There was no statistical association between grade of steatosis and body mass index, fibrosis, necroinflammation, or hyperlipidemia when only HCV genotype 3 patients were included in the multivariate logistic model. Hepatic steatosis is a feature of genotype 3. Patients with HCV genotype 3 are younger and have lower serum cholesterol levels. Genotype 3 is the independent predictor for steatosis in HCV patients. HCV genotype 3 patients with moderate to severe steatosis are more likely to have intravenous drug use as a risk factor.

Background/Aim: Ursodeoxycholic acid in doses of 13–15 mg·kg −1 ·day −1 , is a safe and cost-effective treatment for patients with primary biliary cirrhosis. However, very limited information exists regarding the most appropriate dose of ursodeoxycholic acid. The aim of the study was to compare three dosages of ursodeoxycholic acid with respect to changes in liver biochemistries, Mayo risk score, biliary enrichment with ursodeoxycholic acid and side effects over at least a 1-year period. Methods: A total of 155 patients were randomized to receive low- (5–7 mg·kg −1 ·day −1 ), standard-(13–15 mg·kg −1 ·day −1 ), and high- (23–25 mg·kg −1 ·day −1 ) doses of ursodeoxycholic acid. Results: The improvements in alkaline phosphatase ( p =0.0001), aspartate aminotransferase ( p =0.0001), Mayo risk score ( p =0.002), and ursodeoxycholic acid enrichment ( p =0.0001) were significantly greater in the standard- and high-dose groups compared to the low-dose group, but not between the standard- and high-dose groups. Changes in serum bilirubin were similar between the three groups ( p =0.07). No significant effects on symptoms were noted with any dose. No patients discontinued ursodeoxycholic acid because of side effects or toxicity. Conclusions: Ursodeoxycholic acid in doses of 5–25 mg·kg −1 ·day −1 is safe and well tolerated. The dose of 13–15 mg·kg −1 ·day −1 appears to be the preferred dose for patients with primary biliary cirrhosis.

BRAY, GEORGE A., GEORGE L. BLACKBURN, JAMES M. FERGUSON, FRANK L. GREENWAY, ADESH K. JAIN, CARL M. MENDEL, JOSEPH MEN-DELS, DONNA H. RYAN, SHERWYN L. SCHWARTZ, MONTE L. SCHEINBAUM, AND TIMOTHY B. SEATON. Sibutramine produces dose-related weight loss. Obes Res. Objective Sibutramine is a weight control drug that inhibits the reuptake of both serotonin and norepinephrine. In animals, it reduces food intake and increases thermogenesis and preliminary data in human beings showed weight loss. This paper reports a 24-week dose-ranging study to determine the effect of sibutramine on body weight of patients with obesity. Research Methods and Procedures Seven clinical centers screened 1463 patients with obesity and randomized 1047 to 24 weeks of treatment with 1 of 6 doses of sibutramine (1, 5, 10, 15, 20, or 30 mg) or placebo once daily. Six hundred eighty-three patients completed the study. A two-week placebo run-in period was used to initiate a standardized program of diet, physical activity, and lifestyle changes. Results Weight loss was dose-related and statistically significant vs. placebo (p

Background/Aims: A double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) was conducted in 180 patients with primary biliary cirrhosis (PBC) to define the efficacy and safety of UDCA. Efficacy was assessed by time to treatment failure defined as death; liver transplantation; histological progression; development of varices, ascites, or encephalopathy; doubling of total serum bilirubin levels; progression of fatigue or pruritus; drug toxicity; or voluntary withdrawal. Methods: Patients with well-defined PBC underwent complete history, physical examination, liver chemistries, ultrasonography, upper endoscopy, and liver biopsy at entry as well as at 2 years. Liver chemistries were determined every 3 months. Results: In patients receiving UDCA, treatment failure was delayed compared with the placebo-treated group ( P = 0.0003, log rank test). Seven patients receiving UDCA died or required transplantation compared with 12 in the placebo group ( P = 0.18). No patients discontinued UDCA because of side effects or toxicity. Conclusions: UDCA was extraordinarily safe and well tolerated, and its use was associated with delayed progression of the disease as defined in this study. However, the lack of effects on symptoms, histology, and the need for liver transplantation or survival indicate that further evaluation is necessary to determine the ultimate role of UDCA in the treatment of PBC.

Cyclophosphamide is widely used in the treatment of many vasculitides. Hepatotoxicity associated with such therapy is uncommon but possible. Herein we describe a well-substantiated case of cyclophosphamide-induced hepatotoxicity in a patient with Wegener's granulomatosis. Physicians should be aware of this potentially serious reaction when cyclophosphamide therapy is initiated. Baseline liver function tests and periodic assessment are recommended during treatment with cyclophosphamide.

We enrolled 32 patients with chronic hepatitis C into a randomized, controlled trial to evaluate the efficacy of recombinant alpha-2a-interferon treatment. Sixteen patients were randomized to receive 1.5 million units of recombinant alpha-2a-interferon subcutaneously, thrice weekly, for six months while the remaining 16 patients were randomized to a control group that received no treatment. The mean serum alanine aminotransferase (ALT) level during the six-month study period, expressed as a percentage of the prestudy baseline value, was 82% for the control group compared to 56% for the treatment group (P = 0.014). One fourth of the treatment group normalized their serum ALT level compared to only 6% of the controls (P = 0.05). During posttherapy follow-up, 86% of responders clinically relapsed. Loss of anti-HCV IgM and HCV RNA occurred exclusively in interferon-treated responders. Anti-interferon antibodies developed in 32% of all treated patients. Forty percent of nonresponders developed anti-interferon antibodies compared to only 14% of responders (P = NS). We conclude that recombinant alpha-2a-interferon is clinically effective in patients with chronic hepatitis C. However, most responders in this trial of low-dose interferon relapsed upon cessation of treatment.

One hundred colonoscopies were done. The colonoscopist noted whether the cecum had been intubated as well as the markers used to make this determination. With the colonoscope in position at maximum penetration, a radiologist independently determined its position using fluoroscopy, with a contrast agent delivered through the colonoscope. The cecum was entered in 86 of 100 cases. The tip of the colonoscope was at the level of the ileocecal valve in nine additional cases; the colonoscopist judged that the cecum was well seen in five of these nine. In one case, the colonoscopist overestimated the extent of the examination when transillumination in the right lower quadrant was the only confirming marker. When the more reliable markers (ileocecal valve, appendiceal orifice, converging indentations of the taenia coli in the cecal pole) were seen, no errors were made. Experienced colonoscopists are accurate in assessing the extent of colonoscopy and fluoroscopic confirmation is not routinely needed. When reliable markers are not seen during the examination, a barium enema, preferably with air contrast, should be done.

• Objective. —To determine whether febrile children receiving 2.5-, 5-, or 10-mg/kg ibuprofen therapy via a liquid or 15-mg/kg acetaminophen therapy via an elixir every 6 hours for 24 to 48 hours show equivalent fever reduction or suffer adverse effects of the drug administered. Design. —Randomized, double-blind, multidose, parallel-group, variable-duration (24 to 48 hours) clinical trial. Setting. —The academically affiliated Children's Hospital in Columbus, Ohio. Participants. —64 febrile (defined as oral or rectal temperature of 39°C to 40.5°C) but otherwise healthy children aged 6 months to 11 years 7 months randomly assigned to one of the four drug regimens. Interventions. —Treatment with either ibuprofen or acetaminophen as described above. Administration of antibiotics or intravenous fluids was allowed only after at least 24 hours of treatment with the assigned drug. Measurements/Main Results. —In 61 of the 64 evaluable patients, treatments were effective and well tolerated during the entire study. While the rates of temperature reduction and maximal reduction of fever after administration of the initial dose were equal for patients receiving 10-mg/kg ibuprofen therapy and 15-mg/kg acetaminophen therapy, and both regimens were more effective than smaller doses of ibuprofen in reducing fever, after the second dose (and continuing to the end of the study) there were no statistically significant differences in temperature response among the treatment groups. Six children were withdrawn from the study, two because of dosing errors, three because of hypothermia (temperature of less than 35.6°C; all three patients were in the acetaminophen group), and one because of gastrointestinal distress (this child was in the group receiving 2.5-mg/kg ibuprofen therapy). No other significant symptoms or adverse laboratory or physical findings were noted. While further confirmatory studies are needed, ibuprofen liquid (10 mg/kg) and acetaminophen elixir (15 mg/kg) administered every 6 hours for 24 to 48 hours appeared to be most effective in reducing fever. These two regimens were equally effective and equally tolerated in febrile children. Lower ibuprofen doses (2.5 and 5 mg/kg) were less effective than acetaminophen and 10-mg/kg ibuprofen therapy after the initial dose but were at least equally effective as these two higher-dose regimens thereafter. (AJDC. 1992;146:626-632)

• Objective. —To compare the antipyretic efficacy of ibuprofen, placebo, and acetaminophen. Design. —Double-dummy, double-blind, randomized, placebo-controlled trial. Setting. —Emergency department and inpatient units of a large, metropolitan, university-based, children's hospital in Michigan. Participants. —37 otherwise healthy children aged 2 to 12 years with acute, intercurrent, febrile illness. Interventions. —Each child was randomly assigned to receive a single dose of acetaminophen (10 mg/kg), ibuprofen (7.5 or 10 mg/kg), or placebo. Measurements/Main Results. —Oral temperature was measured before dosing, 30 minutes after dosing, and hourly thereafter for 8 hours after the dose. Patients were monitored for adverse effects during the study and 24 hours after administration of the assigned drug. All three active treatments produced significant antipyresis compared with placebo. Ibuprofen provided greater temperature decrement and longer duration of antipyresis than acetaminophen when the two drugs were administered in approximately equal doses. No adverse effects were observed in any treatment group. Conclusions. —Ibuprofen is a potent antipyretic agent and is a safe alternative for the selected febrile child who may benefit from antipyretic medication but who either cannot take or does not achieve satisfactory antipyresis with acetaminophen. (AJDC. 1992;146:622-625)

The effect of single 0.25 mg, 0.75 mg, 1.5 mg, and 3.0-mg oral doses of trimoprostil and placebo on the inhibition of meal-stimulated gastric acid secretion was investigated in duodenal ulcer patients. Drug and placebo were administered in a double-blind, randomized, crossover study under fasting conditions. A bactopeptone meal was administered 30 minutes after dosing. Gastric acid output was measured by intragastric titation (pH 5.5) and trimoprostil plasma concentrations were measured by a specific gas chromatography-negative chemical ionization-mass spectrometric method. Meal-stimulated gastric acid secretion was significantly reduced when compared to placebo for one hour after 0.25 mg, 1.5 hours after 0.75 mg, and for 2.5-3.0 hours after both 1.5 mg and 3.0 mg doses. The maximal inhibition of gastric acid ranged from 65% reduction after 0.75 mg to 74% after 1.5 mg to 82% after 3.0-mg doses. Trimoprostil was rapidly absorbed and eliminated; terminal elimination half-life ranged from 21 to 45 minutes. Both maximum concentration and area under the plasma concentration-time curve increased proportionately with an increase in the dose. The concentration-effect data at a given dose were simultaneously fit to a pharmacokinetic/pharmacologic effect model. An IC50 (plasma concentration needed to elicit a 50% inhibition effect) value of 0.2 ng/mL was observed at doses of 0.75 mg to 3.0 mg. Overall, trimoprostil was effective in inhibiting acid output in a dose-related manner in duodenal ulcer patients.

The respiratory stimulant effect of progesterone has been known for many years and has led to the hypothesis that this hormone protects young, premenopausal women from disordered breathing and apnea during sleep. Therefore, sleep, breathing, and gonadal hormone parameters were evaluated for 11 normal, menstruating women during times of high and low progesterone levels. No sleep or breathing parameter changed significantly with varying levels of progesterone. Although normal women show a significant change in progesterone levels across the course of the menstrual cycle, the levels achieved did not produce significant changes in breathing parameters.

A relationship between intestinal giardiasis and ocular inflammatory conditions may result in significant vision loss. The parasitic infestation may not produce gastrointestinal symptoms and since early eradication of the parasite may prevent permanent visual loss, it is important that gastroenterologists as well as ophthalmologists be aware of this association.

When the syndrome consisting of sleep-induced apnea and hypersomnolence is due to upper airway obstruction, the hypersomnolence is believed to be the direct result of deprivation of sleep related to such obstructions. The purpose of this report is to describe a group of four asymptomatic subjects with upper airway obstruction during sleep. These subjects were matched with a group of patients with the syndrome of sleep-induced apnea and hypersomnolence. There were no significant differences between symptomatic and asymptomatic groups in terms of the absolute number of upper airway obstructions (252 vs 231), their mean duration (20.8 vs 25.9 seconds), the mean arterial carbon dioxide tension during sleep (39 vs 39 mm Hg), or the electroencephalographic patterns during sleep. The only variables that emerged as significantly different between the two groups were the weights (128 vs 90 kg; P less than 0.05), the low arterial oxygen pressure (PaO2) on waking (54 vs 80 mm Hg; P less than 0.002), and the lower PaO2 during sleep (47 vs 70 mm Hg; P less than 0.01) in the symptomatic patients. From these data, we conclude that the hypersomnolence in patients with sleep-induced apnea due to upper airway obstruction cannot be explained by deprivation of sleep, and other factors need to be carefully examined in future studies.

Objectives. This study sought to examine the hemodynamic and autonomic dose response to digoxin.Background. Previous studies have demonstrated an increase in contractility and heart rate variability with digitalis preparations. However, little is known about the dose-response to digoxin, which has a narrow therapeutic window.Methods. Nineteen patients with moderate heart failure and a left ventricular ejection fraction

To investigate a possible inhibitory effect of blood drawing through an indwelling forearm vein needle on gastric acid secretion, 11 subjects were studied on four occasions each. The first session was for adapting the subject to the 3-hr collection of gastric juice. In 7 subjects the second through fourth sessions gave three conditions in balanced order: (1) an indwelling forearm vein needle and the withdrawal of 5 or 10 cc of blood every 20 min, (2) only a nonfunctional “dummy” needle implanted subcutaneously in the forearm skin, and (3) the control condition with no needle. In four additional subjects the sessions were identical except that condition (1) involved an indwelling forearm vein needle kept open by a slow infusion of saline solution and no blood was drawn. Phenol red recovery from an initial intragastric injection was measured in all. Results showed that blood drawing, but not saline infusion or venipuncture per se, inhibited gastric acid output.