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Surveillance and diagnosis of parasitic Bonamia ostreae infections in flat oysters (Ostrea edulis) are prerequisites for protection and management of wild populations. In addition, reliable and non-lethal detection methods are required for selection of healthy brood oysters in aquaculture productions. Here we present a non-lethal diagnostic technique based on environmental DNA (eDNA) from water samples and demonstrate applications in laboratory trials. Forty oysters originating from Limfjorden, Denmark were kept in 30 ppt sea water in individual tanks. Water was sampled 6 days later, after which all oysters were euthanized and examined for infection, applying PCR. Four oysters (10%) were found to be infected with B. ostreae in gill and mantle tissue. eDNA purified from the water surrounding these oysters contained parasite DNA. A subsequent sampling from the field encompassed 20 oysters and 15 water samples from 5 different locations. Only one oyster turned out positive and all water samples proved negative for B. ostreae eDNA. With this new method B. ostreae may be detected by only sampling water from the environment of isolated oysters or isolated oyster populations. This non-lethal diagnostic eDNA method could have potential for future surveys and oyster breeding programs aiming at producing disease-free oysters.

Background: Several pathologies, including pharyngitis, are associated with abdominal pain that can mimic appendicitis. We sought to further understand the link between appendicitis-like symptoms and streptococcal (strep) pharyngitis., Methods: All patients undergoing ultrasound imaging for appendicitis in our emergency department during 2013 were reviewed (n = 1572). A total of 207 patients were identified who underwent both ultrasound for appendicitis and testing for strep pharyngitis. Demographic and outcomes data between rule out appendicitis patients who underwent strep testing and those who did not were compared., Results: Strep testing was more common in younger patients (mean age = 8.26 vs 10.26 years P < .001) and evenly matched by gender (104 male, 103 female). Of the 207 patients tested for strep pharyngitis, 8 (3.9%) patients had appendicitis and 35 (16.9%) patients tested positive for strep pharyngitis. No cases of concurrent strep pharyngitis and appendicitis were identified. The negative appendectomy rate in the strep pharyngitis tested group was 38.5% (5/13), compared with 7.7% (23/296) ( P = .003) in the nontested group. The appendicitis rate among the strep tested group was 3.8% (8/207) compared with 20% (273/1365) in the nontested group ( P < .001)., Conclusions: Patients undergoing testing for strep pharyngitis were younger, had lower rates of appendicitis, and had a higher rate of negative appendectomy. A diagnosis of concurrent appendicitis and strep pharyngitis is rare. In cases of patients with sufficient symptoms to warrant testing for strep pharyngitis a diagnosis of appendicitis is less likely and surgical intervention leads to higher negative appendectomy rates.

Background: Ultrasound is preferred over computed tomography (CT) for diagnosing appendicitis in children to avoid undue radiation exposure. We previously reported our experience in instituting a standardized appendicitis ultrasound template, which decreased CT rates by 67.3%. In this analysis, we demonstrate the ongoing cost savings associated with using this template., Methods: Retrospective chart review for the time period preceding template implementation (June 2012-September 2012) was combined with prospective review through December 2015 for all patients in the emergency department receiving diagnostic imaging for appendicitis. The type of imaging was recorded, and imaging rates and ultrasound test statistics were calculated. Estimated annual imaging costs based on pretemplate ultrasound and CT utilization rates were compared with post-template annual costs to calculate annual and cumulative savings., Results: In the pretemplate period, ultrasound and CT rates were 80.2% and 44.3%, respectively, resulting in a combined annual cost of $300,527.70. Similar calculations were performed for each succeeding year, accounting for changes in patient volume. Using pretemplate rates, our projected 2015 imaging cost was $371,402.86; however, our ultrasound rate had increased to 98.3%, whereas the CT rate declined to 9.6%, yielding an annual estimated cost of $224,853.00 and a savings of $146,549.86. Since implementation, annual savings have steadily increased for a cumulative cost savings of $336,683.83., Conclusions: Standardizing ultrasound reports for appendicitis not only reduces the use of CT scans and the associated radiation exposure but also decreases annual imaging costs despite increased numbers of imaging studies. Continued cost reduction may be possible by using diagnostic algorithms., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Trauma is one of the leading causes of pediatric morbidity and mortality with significant patient and economic impacts that necessitate constant study. Significant differences in outcomes and resource use exist between blunt and penetrating mechanisms., Methods: The National Trauma Data Bank was analyzed for patients aged 0-18 y with International Classification of Diseases, 9th Revision injury codes for blunt and penetrating trauma from 2007-2012. Demographic information, causes, treatments, complications, and outcomes were assessed., Results: A total of 748,347 pediatric trauma patients were assessed. Blunt trauma was identified as the cause in 601,898 (80.43%) patients compared with 55,597 (7.4%) patients with penetrating trauma. Blunt trauma patients were younger on average and more likely to be female. Despite having a slightly higher mean injury severity scores, blunt trauma patients had shorter length of stay in the hospital (2.9 versus 4.3 d, P < 0.001), fewer complications (34.8% versus 38.6%, P < 0.001), and a much lower mortality rate (1.3% versus 7.1%, P < 0.001). Blunt trauma patients were more likely to undergo computed tomography scanning but less likely to receive transfusions (1.79% versus 5.5%, P < 0.001) and to undergo exploratory laparotomy (0.9% versus 9.4%, P < 0.001) and thoracotomy (0.07% versus 1.7%, P < 0.001). Variations in outcome and resource use were also noted by age., Conclusions: Compared with penetrating trauma, blunt trauma is more common and patients have shorter length of stay, less complications, lower mortality, and are less likely to need operative intervention or blood transfusion. Resource use also varied by age., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: One-quarter to one half of pediatric appendicitis patients present with ruptured appendicitis and about 3%-25% go on to form postoperative intra-abdominal abscesses. The optimal timing of postoperative imaging for suspected abscess formation has been a subject of debate., Methods: All patients who underwent appendectomy for complex appendicitis and were not discharged before postoperative day (POD) #5 from April 2012-October 2014 were identified. Patients were stratified into groups for comparison as follows: group 1 had postoperative computed tomography (CT) scans before POD#7 (n = 26) and group 2 did not (n = 169). Group 2 was further divided into those who were afebrile (group 2a, n = 106) or febrile (group 2b, n = 63) at POD#5., Results: A total of 195 patients met criteria. Early use of CT scans resulted in more drainage procedures (group 1, 73.1% versus group 2b, 28.6%, P < 0.001) and a higher recurrent CT scan rate (38.5% versus 9.5%). The groups had equivalent lengths of stay (11.9 versus 9.8 d, P = 0.10) and readmission rates due to abscesses (19.2% group 1 versus 6.3%, group 2b, P = 0.12) with no septic events. In total, 130 of the 169 patients (76.9%) in group 2 had resolution of symptoms before discharge without intervention with readmission for abscess in only 5.9%., Conclusions: Waiting until POD#7 before scanning led to fewer drainage procedures and recurrent CT scans without increasing length of stay or readmission rates. Most complex appendicitis patients still admitted at POD#5 had resolution of symptoms without need for intervention., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Mutational analysis of Sulfolobus solfataricus class II α-mannosidase was focused on side chains that interact with the hydroxyls of the -1 mannosyl of the substrate (Asp-534) or form ligands to the active site divalent metal ion (His-228 and His-533) judged from crystal structures of homologous enzymes. D534A and D534N appeared to be completely inactive. When compared to the wild-type enzyme, the mutant enzymes in general showed only small changes in K(M) for the substrate, p-nitrophenyl-α-mannoside, but elevated activation constants, K(A), for the divalent metal ion (Co²⁺, Zn²⁺, Mn²⁺, or Cd²⁺). Some mutant enzyme forms displayed an altered preference for the metal ion compared to that of the wild type-enzyme. Furthermore, the H228Q, H533E, and H533Q enzymes were inhibited at increasing Zn²⁺ concentrations. The catalytic rate was reduced for all enzymes compared to that of the wild-type enzyme, although less dramatically with some activating metal ions. No major differences in the pH dependence between wild-type and mutant enzymes were found in the presence of different metal ions. The pH optimum was 5, but enzyme instability was observed at pH <4.5; therefore, only the basic limb of the bell-shaped pH profile was analyzed.

Purpose: Beginning in 2003, the pediatric emergency medicine (PEM) physician replaced the surgeon as the team leader for all level II trauma resuscitations at a busy pediatric trauma center. The purpose was to review the outcomes 10 years after implementing this practice change., Methods: Trauma registry data for all level II activations requiring admission were extracted for the 21 months (April 1, 2001-December 31, 2002) prior to policy change (period 1, **n=627) and compared to the admitted patients from the 10 subsequent years (2003-2013; period 2, n=2694). Data included demographics, length of stay (LOS), injury severity score (ISS), readmissions, complications, and mortality., Results: Mean ISS scores for admitted patients during period 1 (8.5) were higher than during period 2 (7.8). During period 1, 53.6% of patients underwent abdominal CT versus 41.8% in period 2 (p<.001), and the median ED LOS was 135 versus 191 minutes in period 2. From 2000 to 2003, 91% of patients seen as level II trauma alerts were admitted compared to 56.6% of patients in period 2 (p<0.001). There were no missed abdominal injuries identified, and readmission rate was low., Conclusions: We conclude that level II trauma resuscitations can be safely evaluated and managed without immediate surgeon presence. Although ED LOS increased, admission rate and CT scan usage decreased significantly without an increase in missed injuries., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Computed tomography (CT) for the diagnosis of appendicitis is associated with radiation exposure and increased cost. In an effort to reduce the diagnostic use of CT scans, we implemented a standardized ultrasound report template based on validated secondary signs of appendicitis., Methods: In September 2012, as part of a quality improvement project, we developed and introduced a four category standardized ultrasound report template for limited right lower quadrant abdominal ultrasounds. Outcomes for patients undergoing ultrasound or CT scan for appendicitis between 9/10/2012 and 12/31/2013 (Period 2, n=2033) were compared to the three months prior to implementation (Period 1, n=304)., Results: In Period 1, 78 of 304 (25.7%) patients had appendicitis versus 385 of 2033 (18.9%) in Period 2 (p=0.006). Non-diagnostic exams decreased from 48% to 0.1% (p<0.001). Ultrasound sensitivity improved from 66.67% to 92.2% (p<0.001). Specificity did not significantly change (96.9% to 97.69%, p=0.46). CT utilization for appendicitis decreased from 44.3% in Period 1 to 14.5% at the end of Period 2 (p<0.001)., Conclusions: Implementation of a standardized ultrasound report template based on validated secondary signs of appendicitis nearly eliminated non-diagnostic exams, improved diagnostic accuracy, and resulted in a striking decrease in CT utilization., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We have measured infrared spectra from several types of calcite: chalk, freshly cultured coccoliths produced by three species of algae, natural calcite (Iceland Spar), and two types of synthetic calcite. The most intense infrared band, the asymmetric carbonate stretch vibration, is clearly asymmetric for the coccoliths and the synthetic calcite prepared using the carbonation method. It can be very well fitted by two peaks: a narrow Lorenzian at lower frequency and a broader Gaussian at higher frequency. These two samples both have a high specific surface area. Density functional theory for bulk calcite and several calcite surface systems allows for assignment of the infrared bands. The two peaks that make up the asymmetric carbonate stretch band come from the bulk (narrow Lorenzian) and from a combination of two effects (broad Gaussian): the surface or near surface of calcite and line broadening from macroscopic dielectric effects. We detect water adsorbed on the high surface area synthetic calcite, which permits observation of the chemistry of thin liquid films on calcite using transmission infrared spectroscopy. The combination of infrared spectroscopy and density functional theory also allowed us to quantify the amount of polysaccharides associated with the coccoliths. The amount of polysaccharides left in chalk, demonstrated to be present in other work, is below the IR detection limit, which is 0.5% by mass.

Barley α-amylase isozyme 1 (AMY1, EC 3.2.1.1) contains two surface binding sites, SBS1 and SBS2, involved in the degradation of starch granules. The distinct role of SBS1 and SBS2 remains to be fully understood. Mutational analysis of Tyr-380 situated at SBS2 previously revealed that Tyr-380 is required for binding of the amylose helix mimic, β-cyclodextrin. Also, mutant enzymes altered at position 380 displayed reduced binding to starch granules. Similarly, binding of wild type AMY1 to starch granules was suppressed in the presence of β-cyclodextrin. We investigated the role of SBS2 by comparing kinetic properties of the wild type AMY1 and the Y380A mutant enzyme in hydrolysis of amylopectin, amylose and β-limit dextrin, and the inhibition by β-cyclodextrin. Progress curves of the release of reducing ends revealed a bi-exponential hydrolysis of amylopectin and β-limit dextrin, whereas hydrolysis of amylose progressed mono-exponentially. β-Cyclodextrin, however, inhibited only one of the two reaction rates of amylopectin and β-limit dextrin hydrolysis, whereas hydrolysis of amylose was unaffected. The Y380A enzyme showed no detectable inhibition by β-cyclodextrin but displayed similar kinetics to the inhibited wild type AMY1. These results point to SBS2 as an important binding site in amylopectin depolymerization., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The active site for the family GH38 class II α-mannosidase is constituted in part by a divalent metal ion, mostly Zn(2+), as revealed in the crystal structures of enzymes from both animal and bacterial sources. The metal ion coordinates to the bound substrate and side chains of conserved amino acid residues. Recently, evidence has accumulated that class II α-mannosidase is active in complex with a range of divalent metal ions. In the present work, with employment of the class II α-mannosidase, ManA, from the hyperthermophilic archaeon Sulfolobus solfataricus, we explored the influence of the divalent metal ion on the associated steady-state kinetic parameters, K(M) and k(cat), for various substrates. With p-nitrophenyl-α-d-mannoside as a substrate, the enzyme showed activity in the presence of Co(2+), Cd(2+), Mn(2+), and Zn(2+), whereas Ni(2+) and Cu(2+) were inhibitory and nonactivating. Co(2+) was the preferred metal ion, with a k(cat)/K(M) value of about 120 mM(-1) s(-1), 6 times higher than that with Cd(2+) and Zn(2+) and 10 times higher than that with Mn(2+). With α-1,2-, α-1,3-, α-1,4-, or α-1,6-mannobiose as a substrate, Co(2+) was the only metal ion promoting hydrolysis of all substrates; however, Mn(2+), Cd(2+), and Zn(2+) could substitute to a varying extent. A change in the divalent metal ion generally affected the K(M) for the hydrolysis of p-nitrophenyl-α-d-mannoside; however, changes in both k(cat) and K(M) for the hydrolysis of α-mannobioses were observed, along with changing preferences for the glycosidic linkage. Finally, it was found that the metal ion and substrate bind in that order via a steady-state, ordered, sequential mechanism.

Introduction: Regaining basic mobility independence is considered important for elderly hospitalised patients. The Cumulated Ambulation Score (CAS) is a valid tool for evaluating these patients' basic mobility (getting in and out of bed, sit-to-stand from a chair and walking) in orthopaedic wards, and its use is recommended in Denmark for patients with hip fracture. The aims of the present study were to evaluate the feasibility of the CAS in a geriatric ward and to describe its use after hip fracture in Denmark., Material and Methods: A total of 101 consecutive patients (with a mean age of 84.9 (standard deviation 7.2) years) were evaluated with the CAS upon admission and at discharge from a geriatric ward, while data concerning the use of the CAS after hip fracture were collected from national Danish reports., Results: All geriatric patients could be evaluated with the CAS. A total of 41% were independent in terms of basic mobility at admission and 83% of patients at discharge from the ward (p < 0.001). Patients who were not independent in basic mobility upon admission died more often during admission or were more often not discharged to their own home than patients who were independent in basic mobility. National data from the year 2010 showed that the CAS was reported by 21 (78%) of the 27 hospitals and used in 92% of the hospitals that will be treating patients with hip fracture in the future., Conclusion: In geriatric wards, the CAS is a feasible tool for evaluating all patients' basic mobility, and we recommend that it be used in other settings and at all hospitals treating patients with hip fracture.

Determination of the thiol-disulfide status in biological systems is challenging as redox pools are easily perturbed during sample preparation. This is particularly pertinent under neutral to mildly alkaline conditions typically required for alkylation of thiols. Here we describe the synthesis and properties of a thiol-specific reagent, fluorescent cyclic activated disulfide (FCAD), which includes the fluorescein moiety as fluorophore and utilizes a variation of thiol-disulfide exchange chemistry. The leaving-group character of FCAD makes it reactive at pH 3, allowing modification at low pH, limiting thiol-disulfide exchange. Different applications are demonstrated including picomolar thiol detection, determination of redox potentials, and in-gel detection of labeled proteins., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Since interleukin (IL)-18 is a proinflammatory cytokine, mice lacking IL-18 or its ligand-binding receptor (IL-18R) should exhibit decreased cytokine and chemokine production. Indeed, production of IL-1alpha, IL-6, and MIP-1alpha was reduced in IL-18 knock-out (ko) mouse embryonic fibroblast (MEF)-like cells. Unexpectedly, we observed a paradoxical 10-fold increase in IL-1beta-induced IL-6 production in MEF cells from mice deficient in the IL-18R alpha-chain (IL-18Ralpha) compared with wild type MEF. Similar increases were observed for IL-1alpha, MIP-1alpha, and prostaglandin E2. Likewise, coincubation with a specific IL-18Ralpha-blocking antibody augmented IL-1beta-induced cytokines in wild type and IL-18 ko MEF. Stable lines of IL-18Ralpha-depleted human A549 cells were generated using shRNA, resulting in an increase of IL-1beta-induced IL-1alpha, IL-6, and IL-8 compared to scrambled small hairpin RNA. In addition, we silenced IL-18Ralpha with small interfering RNA in primary human blood cells and observed up to 4-fold increases in the secretion of lipopolysaccharide- and IL-12/IL-18-induced IL-1beta, IL-6, interferon-gamma, and CD40L. Mechanistically, despite increases in Stat1 and IL-6, induction of SOCS1 and -3 (suppressor of cytokine signaling 1 and 3) was markedly reduced in the absence of IL-18Ralpha. Consistent with these observations, activation of the p38alpha/beta and ERK1/2 MAPKs and of protein kinase B/Akt increased in IL-18Ralpha ko MEF, whereas the negative feedback kinase MSK2 was more active in IL-18 ko cells. These data reveal a role for SOCS1 and -3 in the seemingly paradoxical hyperresponsive state in cells deficient in IL-18Ralpha, supporting the concept that IL-18Ralpha participates in both pro- and anti-inflammatory responses and that an endogenous ligand engages IL-18Ralpha to deliver an inhibitory signal.

Background: While social differences in childhood injuries are recognized, less is known about how social and demographic differences relate to injury mechanism. The purpose of the study was to reveal how sociodemographic factors affect the incidence of unintentional home injuries in Danish children for specific injury mechanisms and involved products., Methods: Information on injuries in 173 504 children treated at emergency departments was recorded for the period 1998-2003. The information was linked to data including parents' education and income and family type, and the results were compared with those for a random sample of the population., Results: A total of 50 561 injuries were analysed. The risk was 1.5 (1.5-1.6) for children with mothers having only primary education compared to tertiary education, and 1.5 (1.4-1.6) for children in families with the lowest vs. the highest income. Risk differences were found for all injury mechanisms; however the risk for burns was 1.9 (1.6-2.3) times higher in the lowest-income group than in the highest-income group, the relative risk for poisoning was 1.7(1.4-2.1). For scalds from hot water, tea or coffee, the relative risk for the lowest-income group was 2.4(1.8-3.2). Living in a one- or two-parent family and size of the dwelling had little or no effect on risk., Conclusion: Childhood injury incidence depended on sociodemographic factors. The effect of the sociodemographic factors varied between injury mechanisms and products involved in the injury.

Peptidyl deformylase (PDF) is a metallo protease that catalyzes the removal of a formyl group from the N-termini of prokaryotic prepared polypeptides, an essential step in bacterial protein synthesis. Screening of our compound collection using Staphylococcus aureus PDF afforded a very potent inhibitor with an IC(50) in the low nanomolar range. Unfortunately, the compound that contains a hydroxamic acid did not exhibit antibacterial activity (MIC). In order to address the lack of activity in the MIC assay and to determine what portion of the molecule was responsible for binding to PDF, we prepared several analogues. This paper describes our findings that the hydroxamic acid functionality found in 1 is mainly responsible for the high affinity to PDF. In addition, we identified an alternative class of PDF inhibitors, the N-hydroxy urea 18, which has both PDF and antibacterial activity.

Appropriate antidepressant dosing and trial duration are crucial for successful treatment of depression. Before prescribing an antidepressant, primary care physicians should take into account each patient's history, responses to previous antidepressants, depressive symptoms, coexisting illnesses, and current prescriptions. Physicians must be able to help patients manage side effects and know when to discontinue treatment, switch antidepressants, or refer patients to a psychiatrist.

There are several reports of familial testicular cancer in the literature but few systematic attempts have been made to estimate the risk of testicular cancer in first-degree relatives of patients with this neoplasm, and the risk remains to be fully assessed in population-based studies. By means of data from the Danish Cancer Registry, we identified all testicular cancer patients (index cases) born and diagnosed during 1950-1993 in Denmark. Their fathers were identified from national registries, as were the brothers of a subcohort of these patients. Familial cancer occurrence was determined through linkage with the cancer registry and compared with the cancer incidence in the general male population in Denmark. The ratio of observed to expected cancers generated the measure used for the relative risk. Fathers of 2,113 index cases with testicular cancer experienced an almost 2-fold risk of developing testicular cancer themselves (RR = 1.96; 95% CI: 1.01-3.43). Overall, the fathers had a decreased relative cancer risk (RR = 0.84; 95% CI: 0.74-0.95) with a significantly decreased risk of cancers of the lung and digestive organs. Brothers of a subcohort of 702 index cases showed a markedly increased risk of testicular cancer (RR = 12.3; 95% CI: 3.3-3 1.5). In conclusion, we documented a significantly increased familial risk of testicular cancer which was relatively more pronounced between brothers than between fathers and sons. These findings support the possible involvement of a genetic component in the aetiology of testicular cancer, but also leave room for a hypothesized influence of in-utero exposures, such as specific maternal hormone levels, that might be shared by brothers.

A prospective comparison of office blood pressure, daytime ambulatory blood pressure and urinary albumin excretion was performed in 284 consecutive patients from general practice with newly diagnosed, untreated mild to moderate hypertension. Based on daytime ambulatory blood pressure 173 were classified as established hypertensives and 111 as white coat hypertensives. A sample of 127 subjects drawn from the Danish national register served as a normotensive control group. It was found that urinary albumin/creatinine ratio differed significantly between the three groups; the difference remained significant after correction for covariables. Early morning urine albumin/creatinine ratio was weakly but significantly correlated to blood pressure. Early morning urine albumin/creatinine ratio was as reproducible a measure as 24-hour albumin excretion. It is concluded that white coat hypertensive patients have less renal involvement than patients with established hypertension, but more than a normotensive control group.

We compared urinary albumin excretion in normotensive subjects and patients with white coat and established hypertension. The study involved prospective comparison of office blood pressure, daytime ambulatory blood pressure, and urinary albumin excretion in consecutive patients (n = 284) who were selected from general practice with newly diagnosed mild to moderate hypertension before the institution of pharmacologic antihypertensive therapy. All patients had a diastolic office blood pressure above 90 mm Hg; 173 had a consistently elevated diastolic blood pressure (established hypertension), and 111 had an average daytime ambulatory blood pressure below 90 mm Hg (white coat hypertension). A sample of 127 subjects drawn from the Danish national register served as a normotensive control group. The main outcome measure was the ratio of early morning urinary albumin to creatinine. This ratio differed significantly among the three groups, being (on a molar basis) 21 +/- 69 x 10(-6) in the normotensive subjects, 22 +/- 39 x 10(-6) in the white coat hypertensive patients, and 51 +/- 177 x 10(-6) in patients with established hypertension. The difference remained significant after correction for covariables. The ratio of early morning urinary albumin to creatinine was weakly but significantly correlated to blood pressure, was more pronounced for ambulatory than for office measurements, was more pronounced for systolic than for diastolic pressure, and was more pronounced for hypertensive than for normotensive individuals. The ratio was as reproducible a measure as 24-hour albumin excretion. We conclude that white coat hypertensive patients have less renal involvement than patients with established hypertension but more than a normotensive control group.

This study was designed to compare the cardiac mass and geometry in white coat hypertensive patients and established hypertensive patients through the prospective comparison of office blood pressure, daytime ambulatory blood pressure, and echocardiographically determined left ventricular mass and cardiac geometry in consecutive patients. We studied 143 patients from general practice in an outpatient hypertension unit. The patients had newly diagnosed mild-to-moderate hypertension prior to the institution of pharmacological anti-hypertensive therapy. All patients had a diastolic office blood pressure above 90 mm Hg; 90 had a consistently elevated diastolic blood pressure (established hypertension), whereas 53 had an average daytime ambulatory blood pressure below 90 mm Hg (white coat hypertension). Left ventricular mass index was significantly higher in the group with established hypertension, 102.4 +/- 26.6 g/m2 (mean +/- SD) v 93.6 +/- 23.5 (P = .045). Relative wall thickness was likewise significantly higher, 0.36 +/- 0.07 v 0.33 +/- 0.06 (P = .004). There was no significant difference in left atrial dimension. In a multiple regression model the ambulatory measurements and not the office measurements were statistically significantly associated with the extent of cardiac hypertrophy. Further, 44/53 (83%) of the patients with white coat hypertension had normal left ventricular dimensions, versus only 55/90 (61%) of the patients with established hypertension (P = .033). Thus, white coat hypertensive patients display less cardiac involvement than patients with established hypertension, indicating that they should rather be treated as normotensives than as hypertensives, ie, not with pharmacological antihypertensive therapy.

U-54494A, 3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzamide, has been shown to be a potent and long-acting anticonvulsant without analgesic or sedative effects on intact animals. The persistence of anticonvulsant activity after a decline in its concentration in the brain implies the conversion of the parent drug into active metabolites. In this study, two major metabolites of U-54494A, U-83892E [cis-N-(2-aminocyclohexyl)-3,4-dichlorobenzamide] and U-83894A [cis-N-(2-methylaminocyclohexyl)-3,4-dichlorobenzamide], were identified. The synthetic metabolites displayed anticonvulsant activity against electric shock in experimental animals and blocked voltage-gated sodium channel in N1E-115 neuroblastoma cells in voltage- and use-dependent manner by interacting with the inactivated channels as well as with the channels in the resting state (like the parent compound). These observations may provide one explanation for the long duration of the anticonvulsant activity of the parent compound U-54494A and further underscore the importance of voltage-dependent sodium channels in neuronal excitability, especially during seizures.

A microtiter plate format previously reported for the biochemical characterization of microorganisms was modified by adding agar to all of the different test media instead of using a combination of liquid and solid media. This modification, termed the Modified Microtiter Plate procedure (MMP), offered the same advantages of the original method (labor saving, inexpensive, and custom designed for special needs) as well as having the added advantages of longer term storage prior to use and ease of handling. In this study, 60 bacterial isolates (both Listeria suspects and known Listeria cultures) were biotyped using the MMP protocol and compared to results obtained using the classical tube-based US-FDA recommended protocol as the standard identification method and the BBL-Minitek system.

Hooded-Lister rats were inoculated with 6, 25, 50 or 100 metacercariae of the intestinal trematode Echinostoma caproni. Worm establishment and the pattern of egg excretion were followed during the course of primary infections with 6, 25 and 50 metacercariae. Peripheral blood eosinophilia was followed at all infection levels. After 1 month, worm recovery and faecal egg output showed a gradual decline with increasing duration of infection. High worm burdens were expelled later than smaller worm burdens, and egg output persisted longer in animals exhibiting a high initial egg output. The level of blood eosinophilia increased with increasing degree of infection and with the level of egg output. A marked concomitant resistance to superimposed infection was observed on the challenge of rats harbouring 21- and 49-day-old infections with 50 metacercariae. In addition, rats were partially resistant to secondary infection at challenge day 14 following anthelmintic removal of primary 7-day-old infections with 50 metacercariae and were completely resistant at challenge day 7 following elimination of a primary 14-day-old primary infection.

A bacteriocin produced by Pediococcus acidilactici had an inhibitory and bactericidal effect on Listeria monocytogenes associated with fresh meat. MICs were significantly lower than minimum killing concentrations. When meat was inoculated with L. monocytogenes, the bacteriocin reduced the number of attached bacteria in 2 min by 0.5 to 2.2 log cycles depending upon bacteriocin concentration. Meat treated initially with the bacteriocin resulted in attachment of 1.0 to 2.5 log cycles fewer bacteria than that attained with the control. The bacteriocin, after 28 days of refrigerated storage on meat surfaces, was stable and exhibited an inhibitory effect on L. monocytogenes.

Pregnanolone emulsion, a new steroid anaesthetic agent, was administered intravenously as bolus doses to six young healthy male volunteers in a preliminary pharmacokinetic and pharmacodynamic study. The plasma concentration-time curves fitted a two-compartment model. The elimination half-life was between 0.9 and 1.4 hours, volume of central compartment between 0.95 and 2.10 litres/kg, volume of distribution between 3.75 and 5.58 litres/kg and total body clearance between 1.80 and 3.07 (litres/hour)/kg. The excretion in urine of unchanged pregnanolone was less than 0.1%. The pharmacodynamic properties were found to be similar to those of Althesin, with immediate induction of anaesthesia of short duration. The anaesthetic affected haemodynamics only slightly; minor depression of ventilation, with an increase in PaCO2, occurred in several of the subjects. Excitation of short duration occurred in one subject during induction of sleep and slight involuntary muscle movements in another subject during sleep. It is impossible to draw any clear conclusions of the clinical efficacy and tolerance from this limited normal subject trial, but pregnanolone emulsion seems worthy of further clinical trial.

The anticonvulsive activity (ED50), acute toxicity (LD50), and minimal neurotoxicity (TD50) of diazepam in an emulsion form (Diazemuls) were compared with two different water-based diazepam solutions (Valium and Stesolid). The diazepam preparations were administered intravenously to male mice. After determination of time of peak drug activity, the ED50's were established against pentetrazol-induced convulsions, at peak drug activity. The most important difference between the three diazepam preparations was a significantly higher LD50 of diazemuls (275 mg/kg) compared to valium (49 mg/kg) and stesolid (51 mg/kg). ED50 was: diazemuls 0.24 mg/kg, valium 0.14 mg/kg and stesolid 0.10 mg/kg. The therapeutic indices (LD50/ED50) were thus calculated to be 1146 for diazemuls, 350 for valium and 510 for stesolid. Time of peak drug activity and TD50 were equal for all three drugs. No signs of pain on injection or necrosis were observed following diazemuls, whereas this was common after valium and stesolid.

N-Nitrosobis(2-hydroxypropyl)amine (ND2HPA) is a potent pancreatic carcinogen in hamsters and induces gastrointestinal and respiratory tract cancer in rats. The precursor amines, diisopropanolamine (Di-PA) and triisopropanolamine (Ti-PA), are used in some manufacturing processes and in cosmetic preparations. We have found low levels of ND2HPA in commercial Ti-PA (21-270 ng/g) and in Di-PA (20-1 300 ng/g) and have demonstrated that ND2HPA is formed from Ti-PA and nitrite in a yield comparable to that observed for formation of N-nitrosodiethanolamine (NDELA) from triethanolamine under relatively mild conditions. After reaction for 4 h at 37 degrees C (10 mmol/L amine, 40 mmol/L nitrite, pH 3.0), the ND2HPA yield was 0.51%. The NDELA yield under the same conditions was 0.96%. ND2HPA was determined by gas chromatography-thermal energy analysis (GC-TEA) and GC-high-resolution mass spectrometry (GC-MS) selected ion monitoring of the tert-butyldimethylsilyl (t-BDMS) ether after extraction on a Celite 560 column. The t-BDMS ethers of ND2HPA and NDELA yielded intense, structurally significant peaks at m/z 333.2030 and 305.1716, respectively. The GC-MS procedure provides sensitivity and selectivity comparable to that of GC-TEA.

In 15 patients (ASA I-II) undergoing intraabdominal gynaecological surgery, muscle paralysis for tracheal intubation and surgery was achieved by a combined bolus and demand infusion of vecuronium. The initial loading dose of 67 micrograms kg-1 and the rate of subsequent infusion were determined by evaluation of the tactile twitch response to train-of-four (TOF) stimulation of the ulnar nerve while the neuromuscular blockade obtained was recorded blindly for control on the contralateral arm. A maintenance dose of 4.9 mg h-1 (2.0-7.6 mg h-1) produced a smooth course of blockade with minimum and maximum values of twitch height during infusion of 2% and 12%, respectively. A period of 15.9 min elapsed from the end of infusion to a TOF-ratio of 0.7, when neostigmine 2.5 mg was administered at the point of two palpable twitches to TOF-stimulation. Simple tactile evaluation of peripheral nerve stimulation is sufficient to determine the infusion rate of vecuronium required to produce stable and appropriate neuromuscular blockade during intra-abdominal surgery.

The anaesthetic activity of pregnanolone (a metabolite of progesterone) in emulsion formulation administered intravenously to male mice was compared with that of Althesin. The loss of righting reflex for 15 seconds was used to estimate the anaesthetic effect. The mean anaesthetic dose (AD50) for the pregnanolone emulsion was 5.25 mg/kg and for Althesin, 2.8 mg/kg. The mean lethal dose (LD50) was 44 mg/kg for pregnanolone and 54 mg/kg for Althesin. The sleeping time after pregnanolone was 2.5-3.5 times longer than after Althesin in dosages above 7.5 mg/kg. No signs of pain or local reaction from injection were observed for either of the drugs. The onset of action was fast for both drugs, with only minor signs of excitation, and recovery was rapid and without excitation. The results indicate that the anaesthetic properties of pregnanolone emulsion are very similar to those of Althesin. Further studies will show whether it can fill the major vacuum left in anaesthetic practice after the withdrawal of Althesin.

We studied 20 otherwise healthy women undergoing lower abdominal surgery. Immediately after wound closure, while still anaesthetized, they received either electroacupuncture (EA) or no further treatment. They were allowed pethidine for postoperative analgesia by patient-controlled infusion pump. Signs of postoperative distress (pain, nausea, drowsiness) were evaluated after 2 and 6 h by visual analogue scale scores. The group receiving EA consumed half the quantity of pethidine as that used used by the no treatment group. Two patients in the EA group had no postoperative analgesia in the first 2 h. There was no difference in the assessments of postoperative distress between groups. No patient was aware of having received EA or not.

In a double-blind study, 39 patients (ASA groups I-II,) were given either pancuronium or atracurium as an infusion during surgery. The drugs were given as an initial loading dose of 0.064 mg kg-1 or 0.30 mg kg-1, respectively, followed by an infusion, the rate of which was regulated to produce a constant 95% depression of the evoked twitch response throughout surgery. No significant difference in the number of corrections of the infusion rate per hour was found (4.6 v. 4.9). Mean infusion maintenance doses were 35 and 356 micrograms kg-1 h-1, respectively. The inter-individual variability of maintenance doses for the two drugs did not differ, the coefficients of variation being 0.32 and 0.24. On stopping the infusion, the patients given atracurium recovered to a 15% twitch faster than those given pancuronium. In addition neostigmine produced a quicker recovery in this group. Thus atracurium may be a more satisfactory drug for use by infusion.