Development of an abbreviated symptom score for the neonatal abstinence syndrome.

OBJECTIVE: We sought a shortened MOTHER neonatal abstinence syndrome (NAS) and Finnegan score that would retain comparable performance characteristics of the full instrument. STUDY DESIGN: Retrospective cohort. RESULTS: In total, 124,170 MOTHER NAS scores between August 2007 and May 2016 from 775 infants (≥36 weeks) were examined. Classification and regression tree model identified the most important subsets of the scored variables. A 9-element shortened scale yielded >90% sensitivity and specificity to predict clinical endpoints based on the full 19-element MOTHER NAS score. Conversion of the data sets to the Finnegan score, and applying the same procedure resulted in a nine-element score with similar performance characteristics. CONCLUSION: Shortened scoring instruments were identified with the high-predictive power for clinical endpoints based on the 19-element full MOTHER NAS score. There was no substantial variation in performance for age, supporting the current practice of utilizing a single scoring tool regardless of postnatal age.

Pharmacological and non-pharmacological treatments for the Neonatal Abstinence Syndrome (NAS).

Neonatal abstinence syndrome is defined by signs and symptoms of withdrawal that infants develop after intrauterine maternal drug exposure. All infants with documented in utero opioid exposure, or a high pre-test probability of exposure should have monitoring with a standard assessment instrument such as a Finnegan Score. A Finnegan score of >8 is suggestive of opioid exposure, even in the absence of declared use during pregnancy. At least half of infants in most locales can be treated without the use of pharmacologic means. For this reason, symptom scores will drive the decision for pharmacologic therapy. Nevertheless, all infants, regardless of initial manifestations, should be first be managed with non-pharmacologic approaches which in turn, should not be considered as the sole alternative to drug therapy, but rather, as the base upon which all patients are treated. Those who continue to have symptoms despite supportive care should be pharmacologically treated, which in the most severe cases, is life-saving.

Transgenic avian-derived recombinant human interferon-alpha2b (AVI-005) in healthy subjects: an open-label, single-dose, controlled study.

BACKGROUND/AIMS: This study characterized the safety and pharmacological properties of AVI-005, a novel glycosylated recombinant human interferon-alpha2b produced from the egg whites of chickens transfected with human cDNA. METHODS: 18 healthy volunteers received single subcutaneous rising doses (0.5, 1.66 or 5 million international units, MIU) of AVI-005. A randomized parallel comparator group of 10 subjects received 5 MIU of unglycosylated IFN-alpha2b (Intron A). The pharmacokinetic parameters t1/2, tmax, Cmax, AUC0-24h, Vd, and clearance were compared between AVI-005 and unglycosylated IFN-alpa2b. RESULTS: At equipotent doses, AVI-005 had a larger AUC0-24h than the control interferon. Pharmacodynamic markers ofneopterin and beta2-microglobulin for the two treatments were similar. These markers were increased by AVI-005 in a dose-dependent manner. Pharmacodynamic responses to treatment with AVI-005 were shown by the change in mRNA expression for interferon inducible protein kinase and 2'5'-oligoadenylate synthetase. Adverse events in the two groups were qualitatively and quantitatively similar. CONCLUSION: AVI-005 demonstrates biological activity and pharmaco-kinetic properties in humans that support further development.

The Nephrotoxicity of Vancomycin.

Vancomycin use is often associated with nephrotoxicity. It remains uncertain, however, to what extent vancomycin is directly responsible, as numerous potential risk factors for acute kidney injury frequently coexist. Herein, we critically examine available data in adult patients pertinent to this question. We review the pharmacokinetics/pharmacodynamics of vancomycin metabolism. Efficacy and safety data are discussed. The pathophysiology of vancomycin nephrotoxicity is considered. Risk factors for nephrotoxicity are enumerated, including the potential synergistic nephrotoxicity of vancomycin and piperacillin-tazobactam. Suggestions for clinical practice and future research are given.

Reversibility of Apixaban Anticoagulation with a Four-Factor Prothrombin Complex Concentrate in Healthy Volunteers.

It was hypothesized that the four-factor prothrombin complex concentrate (4F-PCC) Kcentra 25 unit/kg would reverse impairment of thrombin generation in healthy volunteers dosed with apixaban to steady state. In this randomized, two-period crossover, assessor-blinded trial, 12 healthy subjects received 5 mg apixaban every 12 h. Three h after the fifth dose, four-factor prothrombin complex concentrate (4F-PCC) 25 unit/kg or saline were infused. Serial blood samples were assessed for thrombin generation using PPP-reagent and PPP-reagent low, anti-Xa, PT, and PTT assays. Geometric mean ratio was calculated at 30 min postinfusion, and at 24, 48, and 72 h. Peak thrombin generation was 76% higher at 30 min postinfusion with 4F-PCC (p = 0.025). The difference declined to 24% at 24 h and resolved by 48 h. Other thrombin generation parameters were also partially normalized. There was no difference between 4F-PCC and saline in anti-Xa assessment at 30 min or later time points.

A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy.

The literature on the pharmacokinetics of vancomycin in patients undergoing extracorporeal membrane oxygenation (ECMO) therapy is sparse. A population pharmacokinetic (PK) model for vancomycin in ECMO patients was developed using a nonlinear mixed effects modeling on the concentration-time profiles of 14 ECMO patients who received intravenous vancomycin. Model selection was based on log-likelihood criterion, goodness of fit plots, and scientific plausibility. Identification of covariates was done using a full covariate model approach. The pharmacokinetics of vancomycin was adequately described with a two-compartment model. Parameters included clearance of 2.83 L/hr, limited central volume of distribution 24.2 L, and low residual variability 0.67%. Findings from the analysis suggest that standard dosing recommendations for vancomycin in non-ECMO patients are adequate to achieve therapeutic trough concentrations in ECMO patients. This further shows that ECMO minimally affects the PK of vancomycin in adults including in higher-weight patients.

Effect of Vorapaxar Alone and in Combination with Aspirin on Bleeding Time and Platelet Aggregation in Healthy Adult Subjects.

The effect of the protease-activated receptor-1 (PAR-1) antagonist vorapaxar on human bleeding time is not known. This was a randomized, two-period, open-label trial in healthy men (n = 31) and women (n = 5). In period 1, subjects received 81 mg aspirin q.d. or a vorapaxar regimen achieving steady-state plasma concentrations equivalent to chronic 2.5 mg q.d. doses, for 7 days. In period 2, each group added 7 days of the therapy alternate to that of period 1 without washout. Bleeding time and platelet aggregation using arachidonic acid, ADP, and TRAP agonists were assessed. Bleeding time geometric mean ratio (90% CI) for vorapaxar/baseline was 1.01 (0.88-1.15), aspirin/baseline was 1.32 (1.15-1.51), vorapaxar + aspirin/vorapaxar was 1.47 (1.26-1.70), and vorapaxar + aspirin/aspirin was 1.12 (0.96-1.30). Unlike aspirin, vorapaxar did not prolong bleeding time compared with baseline. Bleeding time following administration of vorapaxar with aspirin was similar to that following aspirin alone.

Manufacturer's drug interaction and postmarketing adverse event data: what are appropriate uses?

Governmental agencies overseeing pharmaceutical products use a risk/benefit approach to analyse data and make regulatory decisions. Comprehensive public dissemination of the safety profile of pharmaceutical products is part of an overall strategy for reducing risk associated with the use of any medical product. In the US, reports of postmarketing surveillance of approved drugs are in the public domain. Some, but not all, of the information in drug interaction studies is available to the public through the Freedom of Information Act (FOIA). However, there are concerns over the misuse of these data for commercial or other gain. The need to protect intellectual property and foster innovation in drug development, and concerns of legal liability are often cited as reasons to limit full public access to data from drug development studies. In contrast, intellectual freedom. public safety, and a mandate for transparent decision-making processes by regulatory agencies are issues that support open access to these data. Ultimately. concern for the public safety justifies open access to postmarketing surveillance data, and to a lesser degree, data regarding drug interactions in marketed products, and should outweigh the potential loss of competitive advantage by pharmaceutical companies.

Paradoxical hypotension and bradycardia after intravenous arginine vasopressin.

Standard therapy for variceal bleeding includes endoscopic sclerotherapy and esophageal balloon tamponade. In addition, pharmacologic therapies, including arginine vasopressin (AVP), are frequently used in hemodynamically unstable patients or where sclerotherapy has been unsuccessful. A case is described herein of a 30-year-old woman with a history of ethanol abuse, hematemeisis, and biopsy-proven hepatic cirrhosis in which the addition of AVP to an antivariceal regimen of octreotide was associated with a paradoxical episode of hypotension, bradycardia, and hypoxia. Indeed, within 15 minutes after initiation of an AVP infusion, the patient exhibited hypotension with a systolic blood pressure of 80 mmHg, a relative bradycardia to 76 beats per minute, and a desaturation of blood oxygen to 84%. The AVP infusion was discontinued 2 hours later and blood pressure, heart rate, and oxygen saturation rapidly returned to baseline. This temporal correlation between the onset and termination of the physiologic effects and the initiation and discontinuation of the AVP infusion suggests a causal relationship. The paradoxical physiologic effects might reflect cardiac ischemia secondary to vasospasm and/or central suppression of the autonomic nervous system induced by AVP.

Evaluation of a selective enrichment technique for the isolation of Campylobacter pylori.

To cultivate Campylobacter pylori from contaminated biopsy specimens, Brucella broth was supplemented with 10% fetal calf serum, 1% Vitox, 1000 units/ml polymyxin B sulfate, 10 micrograms/ml vancomycin, and 2 micrograms/ml amphotericin B. Pseudomonas aeruginosa, Candida albicans, and Enterococcus fecalis were cocultivated with C. pylori. All four strains of C. pylori were recoverable at 24 h. When 21 C. pylori strains were studied in pure culture, 86% grew in the selective enrichment medium. In a clinical study, the selective enrichment technique resulted in isolation of C. pylori from 50% of patient samples, compared with isolation from only 36% of samples with agar cultivation. The selective enrichment technique may be more sensitive than techniques currently employed to isolate C. pylori from gastric tissue.

Cytotoxic activity in broth-culture filtrates of Campylobacter pylori.

Broth-culture filtrates of Campylobacter pylori induced non-lethal cytopathic effects in vitro in 7 of 9 mammalian cell lines tested. Transmission electronmicroscopy revealed that the response consisted of intracellular vacuolisation. Intestine 407 cells were among the most responsive and were used for routine assay. About 55% of isolates of C. pylori tested, originating from four geographic regions worldwide, produced cytotoxic activity. The activity was neutralisable by specific antisera to broth-culture filtrates or to sonicated bacteria but not by antisera to other bacterial preparations. Cytotoxic activity was heat-labile (70 degrees C for 30 min), was protease-sensitive and ammonium-sulphate precipitable. It did not pass through an ultrafiltration membrane with a nominal mol.-wt limit of 100 X 10(3). It was concluded that C. pylori can produce a factor that alters cultured cells in vitro. The relevance of this factor to the pathogenesis of gastritis associated with C. pylori remains to be determined.

A simple touch-down polymerase chain reaction for the detection of canine parvovirus and feline panleukopenia virus in feces.

A polymerase chain reaction (PCR) assay is described for the detection of parvovirus in feces of dogs and cats. A touch-down protocol was used which enabled the specific amplification of virion DNA from feces after a fast and simple boiling pretreatment. The sensitivity of PCR was as high as ten infectious particles per reaction which corresponds to a titer of about 10(3) infectious particles per gram of unprocessed feces. This renders the PCR about 10- to 100-fold more sensitive than electron microscopy, the standard method for parvovirus diagnosis. The very rapid and simple sample preparation recommends this PCR assay as an alternative technique for routine parvovirus diagnosis.

Preparation and antimicrobial assessment of 2-thioether-linked quinolonyl-carbapenems.

This reports the synthesis and in vitro antimicrobial properties of a series of 2-thioether-linked quinolonyl-carbapenems. Although the title compounds exhibited broad spectrum activity, the MICs were generally higher than those observed for selected benchmark carbapenems, quinolonyl-penems, and quinolones. Enzyme assays suggested that the title compounds are potent inhibitors of penicillin binding proteins and inefficient inhibitors of bacterial DNA-gyrase. Uptake studies indicated that the new compounds are not substrates for the norA encoded quinolone efflux pump.

Geriatrics in canine and feline internal medicine.

The increasing life expectancy in humans--at least in the developed countries--including all medical, social, and political consequences is a generally accepted phenomenon at the end of this century. In earlier examinations it could be noticed that also in dogs and cats a remarkable increase of the life span seems to occur in the last 15 years (Beelitz 1988; Danckert and Kraft 1997; Davis 1996; Eichelberg and Seine 1996; Goldston 1989; Kraft 1978, 1990, 1997 a-c; Kraft and Danckert 1997; Kraft et al. 1989; Pauling 1990; Trimborn 1990). If this is true, it could have a series of consequences not only for the veterinary practice but also for the comparative medicine. The aim of this paper was to examine a population of dogs and cats to find out, if the life span of these companion animals really increases and the consequences it may have for medical care. The following criteria were examined: (1) the distribution of the age of the dogs and cats at their last presentation as out-patients (2) the change of the age at which the animals died on an average (3) the influence of the breed on the life expectancy (4) the relation of the sex and expectation of life (5) age related multimorbidity (6) the appearance of the most common organ diseases and functional disturbances during the life span

Comparison of T-cell subpopulations in cats naturally infected with feline leukaemia virus or feline immunodeficiency virus.

T-cell subsets were studied by flow cytometry in 58 feline leukaemia virus (FeLV)-positive cats with naturally acquired FeLV infection to determine whether the changes in CD4+ or CD8+ T cell populations differed from those observed in 55 feline immunodeficiency virus (FIV)-positive cats with naturally acquired FIV infection. The sole criterion for inclusion into the study was seropositivity. Mean (SD) CD4+ T cell values of FeLV positive cats were decreased to 31.1 (8.0) per cent and their CD8+ T cell values were increased to 22.8 (6.3) per cent in comparison with uninfected control cats (37.9 [9.5] per cent CD4+; 15.2 [6.3] per cent CD8+). The CD4+/CD8+ ratio was reduced to 1.5 (0.7), compared with 3.0 (1.5) in 39 FeLV-and FIV-negative control cats. Differences from control values were significant, but there was no significant difference between CD4+ and CD8+ lymphocytes of FeLV-versus FIV-infected cats. These findings indicate that FeLV and FIV have similar effects on T lymphocyte subsets. Both retrovirus infections can induce immunodeficiency, both viruses infect a broad range of lymphohaemopoietic cells, despite having different primary target cells, and can induce the killing of lymphocytic cells in vitro. It is concluded that a decreased CD4+/CD8+ ratio is not restricted to FIV infections but may also occur in FeLV infection.

Endothelin concentration in plasma of healthy dogs and dogs with congestive heart failure, renal failure, diabetes mellitus, and hyperadrenocorticism.

Plasma concentrations of endothelin (ET)-1 and -3 were determined simultaneously in dogs with various pathophysiological conditions, because these peptides may display different pharmacological profiles. The study pays special attention to the characterization of plasma ET immunoreactivity (ET-IR), using high-pressure liquid chromatography (HPLC) analysis with off-line detection by radio-immunoassay (RIA). In most sick dogs evaluated total plasma ET-1-IR concentration did not differ from that of healthy dogs. However, HPLC analysis of their total plasma ET-1-IR revealed distinct ET-IR profiles. Big-ET-1, which is barely detectable in control dogs, does represent the predominant ET in sick dogs. Regardless of the pathophysiological conditions, considerable amounts of high-molecular weight ET-1-IR, most likely aggregated ET-material, was found consistently. With respect to ET-3, we constantly observed moderately increased concentrations, though no major difference of molecular pattern was evident between healthy and sick dogs. The data show a distinct regulation of ET-1 and ET-3 in dogs. Furthermore, specific molecular forms of ET-IR were found to occur in various diseases. The endothelins may therefore prove to be of diagnostic importance in the pathophysiology of vascular diseases.

Attitudes of psychiatrists toward diagnostic options and issues.

Debate regarding the control of mental health services has marked the mental health scene for several decades. The debate continued and broadened, however, with the publication of DSM-III. The ubiquitous use of that diagnostic system for third-party reimbursement led some mental health professionals to call attention to the likely possibility that whoever controls diagnosis will also control mental health (O'Keefe 1980). This study sought to gather attitudinal information on psychiatrists' views regarding DSM-III, alternative nosological models, selected adjunct issues related to the medical model and mental illness concepts, and other professional concerns.

Atrial natriuretic peptide concentration in dogs with congestive heart failure, chronic renal failure, and hyperadrenocorticism.

The function of atrial natriuretic peptide (ANP) is claimed to be control of salt and water homeostasis, and thus, the hormone may be involved in the pathogenesis of certain diseases with impaired volume regulation. We, therefore, studied plasma ANP concentration in dogs with chronic renal failure, congestive heart failure, and hyperadrenocorticism. Dogs with chronic renal failure had twofold higher plasma ANP concentration (16.2 +/- 5.8 fmol/ml), compared with healthy dogs (8.3 +/- 3.5 fmol/ml). An even more distinct increase (sixfold) of plasma ANP concentration was found in dogs with congestive heart failure (52.9 +/- 29.7 fmol/ml). In contrast, dogs with hyperadrenocorticism did not have high ANP plasma concentration (5.5 +/- 2.0 fmol/ml). High-performance liquid chromatographic analysis of plasma from dogs with congestive heart failure indicated that, in addition to the normal circulating form of ANP (99-126), the unprocessed precursor ANP (1-126) is detectable in the circulation. These qualitative and quantitative alterations of plasma ANP concentration in dogs further suggest involvement of this peptide in the development and/or maintenance of diseases associated with impaired volume regulation.

Etiology and treatment of dental anxiety and phobia.

Dental anxiety and phobia afflict millions of people. Dental patients who are anxious anticipate pain and feel vulnerable and out of control. Hypnotherapy to alleviate dental anxiety and phobias has received clinical and empirical support. Our purpose in this paper is to provide a body of objective data from American Society of Clinical Hypnosis members regarding incidence rates and the relative importance of various etiological and conceptual issues in the development and maintenance of dental anxiety and treatment interventions. From these data, we constructed a model of etiology, maintenance, and treatment of dental anxiety.

[Development of the age structure of a cat population compared with the dog]. / Entwicklung des Altersaufbaus einer Katzenpopulation im Vergleich zum Hund.

The dogs and cats, treated at the Clinic of Internal Medicine of the University of Munich since 1983 show a tendency to a higher age of life; this is true especially in cats. The age structure of the dog population expresses a tendency to an increase of older individuals since a longer time period, whereas in the cat population this development could not be verified before the year of 1987. The results of this examination require an intensive work on the problems of increasing age, especially with those of multimorbidity, the preponderance of chronic diseases, prophylaxis, nutrition, and posture.