Validity and severity thresholds for the depression subscale of the affective self rating scale: An equipercentile equating study using classical test theory.

BACKGROUND: The Affective Symptoms Scale (ASRS) is a unique instrument designed to separately measure depressive and manic symptoms in mood disorders. We validated the ASRS against the Patient Health Questionnaire (PHQ-9) and the Quick Inventory of Depressive Symptomatology (QIDS-16). METHODS: A retrospective study of 258 patients who completed the PHQ-9, QIDS-16 and ASRS as part of routine clinical care. To establish meaningful clinical thresholds for the depression subscale of the ASRS, it was equated with the QIDS and the PHQ-9. RESULTS: The depression subscale of the ASRS had significant positive correlations with the QIDS-16 and the PHQ-9 (respectively, r= 0.8, t[253] = 19.8, p < 0.001, and r= 0.8, t[245] = 28.2, p < 0.001). The equipercentile equating method with the PHQ-9 indicated that the thresholds corresponded to ASRS depression subscale scores of 5.4, 10.6, 16.1, and 23. Equating with the QIDS indicated that thresholds corresponded to ASRS depression subscale scores of 5.1, 11, 18.4, and 27.5. LIMITATIONS: Limitations include a small sample size that did not allow more detailed statistical analysis, such as Item Response Theory. The population is a heterogenous population at a university outpatient setting. CONCLUSIONS: The ASRS depression subscale significantly correlated with the PHQ-9 and QIDS-16. Our proposed threshold scores for the ASRS are 5, 11, 16 and 23 to indicated mild, moderate, severe and very severe depression respectively.

Perinatal nutrition interacts with genetic background to alter behavior in a parent-of-origin-dependent manner in adult Collaborative Cross mice.

Previous studies in animal models and humans have shown that exposure to nutritional deficiencies in the perinatal period increases the risk of psychiatric disease. Less well understood is how such effects are modulated by the combination of genetic background and parent-of-origin (PO). To explore this, we exposed female mice from 20 Collaborative Cross (CC) strains to protein deficient, vitamin D deficient, methyl donor enriched or standard diet during the perinatal period. These CC females were then crossed to a male from a different CC strain to produce reciprocal F1 hybrid females comprising 10 distinct genetic backgrounds. The adult F1 females were then tested in the open field, light/dark, stress-induced hyperthermia, forced swim and restraint stress assays. Our experimental design allowed us to estimate effects of genetic background, perinatal diet, PO and their interactions on behavior. Genetic background significantly affected all assessed phenotypes. Perinatal diet exposure interacted with genetic background to affect body weight, basal body temperature, anxiety-like behavior and stress response. In 8 of 9 genetic backgrounds, PO effects were observed on multiple phenotypes. Additionally, we identified a small number of diet-by-PO effects on body weight, stress response, anxiety- and depressive-like behavior. Our data show that rodent behaviors that model psychiatric disorders are affected by genetic background, PO and perinatal diet, as well as interactions among these factors.

Characterization of the EP receptor subtype that mediates the inhibitory effects of prostaglandin E2 on IgE-dependent secretion from human lung mast cells.

BACKGROUND: Prostaglandin E2 (PGE2 ) has been shown to inhibit IgE-dependent histamine release from human lung mast cells. This effect of PGE2 is believed to be mediated by EP2 receptors. However, definitive evidence that this is the case has been lacking in the absence of EP2 -selective antagonists. Moreover, recent evidence has suggested that PGE2 activates EP4 receptors to inhibit respiratory cell function. OBJECTIVE: The aim of this study was to determine the receptor by which PGE2 inhibits human lung mast cell responses by using recently developed potent and selective EP2 and EP4 receptor antagonists alongside other established EP receptor ligands. METHODS: The effects of non-selective (PGE2 , misoprostol), EP2 -selective (ONO-AE1-259, AH13205, butaprost-free acid) and EP4 -selective (L-902,688, TCS251) agonists on IgE-dependent histamine release and cyclic-AMP generation in mast cells were determined. The effects of EP2 -selective (PF-04418948, PF-04852946) and EP4 -selective (CJ-042794, L-161,982) antagonists on PGE2 responses of mast cells were studied. The expression of EP receptor subtypes was determined by RT-PCR. RESULTS: Prostaglandin E2 , EP2 agonists and EP4 agonists inhibited IgE-dependent histamine release from mast cells. PGE2 and EP2 agonists, but not EP4 agonists, increased cyclic-AMP levels in mast cells. EP4 -selective antagonists did not affect the PGE2 inhibition of histamine release, whereas EP2 -selective antagonists caused rightward shifts in the PGE2 concentration-response curves. RT-PCR studies indicated that mast cells expressed EP2 and EP4 receptors. CONCLUSIONS AND CLINICAL RELEVANCE: Although human lung mast cells may express both EP2 and EP4 receptors, the principal mechanism by which PGE2 inhibits mediator release in mast cells is by activating EP2 receptors.

Assessment of NMDA receptor activation in vivo by Fos induction after challenge with the direct NMDA agonist (tetrazol-5-yl)glycine: effects of clozapine and haloperidol.

Induction of Fos protein by the potent and direct NMDA agonist (tetrazol-5-yl)glycine (TZG) was examined in mice. Effects of antipsychotic drugs were assessed on this in vivo index of NMDA receptor activation. TZG induced the expression of Fos in a neuroanatomically selective manner, with the hippocampal formation showing the most robust response. In mice genetically altered to express low levels of the NR1 subunit of the NMDA receptor, TZG-induced Fos was reduced markedly in comparison to the wild type controls. TZG-induced Fos was also blocked by the selective NMDA antagonist MK-801. Pretreatment of mice with clozapine (3 and 10 mg/kg) reduced TZG-induced Fos in the hippocampal formation but not in other brain regions. Haloperidol at a dose of 0.5 mg/kg did not antagonize TZG induced Fos in any region. Haloperidol at a dose of 1.0 mg/kg did attenuate the induction of Fos by TZG in the hippocampus but not in other brain regions. The relatively high dose (1 mg/kg) of haloperidol required to block effects of TZG suggests that this action may not be related to the D(2) dopamine receptor-blocking properties, since maximal D(2) receptor blockade was probably achieved by the 0.5 mg/kg dose of haloperidol. The antidepressant drug imipramine (10 or 20 mg/kg) did not antagonize TZG induced Fos in any brain region. The data suggest that clozapine can reduce excessive activation of NMDA receptors by TZG administration in vivo at doses relevant to the drugs' actions in rodent models of antipsychotic activity. Whether or not this action of clozapine contributes to its therapeutic properties will require further study.

Dietetic guidelines: diet in secondary prevention of cardiovascular disease (first update, June 2003).

AIM: To update dietetic guidelines summarizing the systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention). METHODS: The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to November 2002 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomised controlled trials relating to diet and secondary prevention of CVD. Two members of the UK Heart Health and Thoracic Dietitians Group critically appraised each review. The quality and results of each review were discussed and summarized in a meeting of the whole group. RESULTS: Providing evidence-based dietary information (including increasing omega-3 fat intake) to all people who have had a myocardial infarction will save more lives than concentrating dietary advice on just those in need of weight loss or lipid lowering. The practice of prioritizing dietetic time in secondary prevention to those with raised lipids is out of date since the advent of statin therapy. However, effective dietary advice for those with angina, stroke, peripheral vascular disease or heart failure is less clear. CONCLUSION: There is good systematic review evidence that dietary advice to those with coronary heart disease can reduce mortality and morbidity as well as modify some risk factors. Dietary advice that does this most effectively should be prioritized.

Marine protozoa produce organic matter with a high affinity for PCBs during grazing.

Processes influencing organic carbon distribution and composition can control the speciation of organic contaminants such as polychlorinated biphenyls (PCBs) and ultimately determine their residence time in aquatic environments. Protozoan grazers are active in the remineralization and recycling of organic material both in the water column and at the sediment-water interface. Thus, they influence the quality and quantity of potential PCB binding substrates in the suspended and dissolved phases of aqueous systems. In this study, common headspace systems were used to compare the chlorobiphenyl-binding affinity of dissolved organic carbon (DOC) in protozoan and bacterial culture filtrates (<0.2 microm) relative to DOC in a seawater control. Culture filtrates from three marine protozoan species were compared-Uronema sp., Cafeteria sp., and Paraphysomonas imperforata. Each protozoan species was fed the same bacterial prey, Halomonas halodurans, which was also used as a bacterial control. Affinities of culture DOC for [14C]3,3',4,4'-tetrachlorobiphenyl (IUPAC 77) were normalized to DOC and surfactant concentrations. Values of DOC equilibrium partition coefficients (K(DOC)) ranged from 10(4.6) in seawater (Vineyard Sound, MA) to 10(5.4) and 10(5.5) in protist cultures, indicating that grazer-modified DOC was a better sorbent for PCBs than DOC in bacterial or seawater controls.

Importance of passive diffusion in the uptake of polychlorinated biphenyls by phagotrophic protozoa.

Unicellular protozoan grazers represent a size class of organisms where a transition in the mechanism of chlorobiphenyl (CB) introduction, from diffusion through surface membranes to ingestion of contaminated prey, could occur. This study compares the relative importance of these two processes in the overall uptake of polychlorinated biphenyls by protists. Uptake rates and steady-state concentrations were compared in laboratory cultures of grazing and nongrazing protozoa. These experiments were conducted with a 10-microm marine scuticociliate (Uronema sp.), bacterial prey (Halomonas halodurans), and a suite of 21 CB congeners spanning a range of aqueous solubilities. The dominant pathway of CB uptake by both grazing and nongrazing protozoa was diffusion. Organic-carbon-normalized CB concentrations (in the protozoan cell) were equivalent in grazing and nongrazing protozoa for all congeners studied. Rate constants for uptake into and loss from the protozoan cell were independently determined by using [3,3',4, 4'-(14)C]tetrachlorobiphenyl (IUPAC no. 77), 0.38 +/- 0.03 min(-1) and (1.1 +/- 0.1) x 10(-5) (g of organic carbon)(-1) min(-1), respectively. Magnitudes of the uptake and loss processes were calculated and compared by using a numerical model. The model result was consistent with data from the bioaccumulation experiment and supported the hypothesis that diffusive uptake is faster than ingestive uptake in phagotrophic unicellular protozoa.

Ability of laboratory methods to predict in-use efficacy of antimicrobial preservatives in an experimental cosmetic.

Volume 60, no. 12, p. 4553: a present address for S. J. Wells should be given, as follows: (dag) Present address: Cadbury Beverages North America, Trumbull, CT 06611. [This corrects the article on p. 4553 in vol. 60.].

The role of ciprofloxacin in a patient with delirium due to multiple etiologies.

A 40-year-old female with a lumbar drain was admitted to the neurosurgery service with a bacterial meningitis. During the course of her treatment with multiple central nervous system (CNS) active medications, the patient became disoriented and agitated with visual hallucinations and generalized myoclonus. A psychiatric consultation was requested. The case is presented and discussed within the context of the importance of understanding etiological mechanisms in treating and reversing delirium. The fluoroquinolone agent ciprofloxacin was considered to be the primary etiology of the patient's delirium. This class of medication as a cause of altered mental status is discussed.

Ability of laboratory methods to predict in-use efficacy of antimicrobial preservatives in an experimental cosmetic.

The abilities of nine antimicrobial systems to preserve an experimental water-based cosmetic formulation were evaluated by six microbiological challenge tests: the U.S. Pharmacopeia test; the British Pharmacopeia test; the Cosmetic, Toiletry, and Fragrance Association test; the rapid screen test; the sequential challenge test; and the post-use test. The antimicrobial systems contained various combinations and amounts of two parabens and a quaternary compound in order to provide a broad range of preservation. The results obtained were compared with the abilities of the formulations to support maintenance and growth of microorganisms in microfloras obtained from human axilla areas and finger skin during an 8-week simulated in-use test. Without statistical analysis all of the tests predicted the results obtained with well-preserved or poorly preserved formulations. The rapid screen test was the best test for predicting differences at intermediate levels of preservation. Statistically, all of the tests were equivalent predictors of preservation efficacy in the in-use test (P = 0.05). At the P = 0.10 level, only the U.S. Pharmacopeia, British Pharmacopeia, rapid screen, Cosmetic, Toiletry, and Fragrance Association tests were significantly predictive. The results of prediction by a test, based on the preservative levels used, agreed well with the in-use test results (P = 0.01). A total of 20% of the formulations that contained excessive microbial levels contained human axilla microorganisms. The levels of preservation in failed products were similar to the levels of preservation in unused controls.

Influence of infusion pump operation and flow rate on hemodynamic stability during epinephrine infusion.

OBJECTIVE: To determine whether variations in the flow rate of epinephrine solutions administered via commonly available infusion pumps lead to significant variations in blood pressure (BP) in vivo. DESIGN: Prospective, randomized, crossover study with factorial design, using infusion pumps with four different operating mechanisms (pulsatile diaphragm, linear piston/syringe, cyclic piston-valve, and linear peristaltic) and three drug delivery rates (1, 5, and 10 mL/hr). SUBJECTS: Two healthy, mixed-breed dogs (12 to 16 kg). INTERVENTIONS: Dogs were made hypotensive with methohexital bolus and continuous infusion. BP was restored to normal with constant-dose epinephrine infusion via two pumps at each rate. MEASUREMENTS: Femoral mean arterial pressure (MAP) was recorded every 10 secs. Pump-flow continuity was quantitated in vitro using a digital gravimetric technique. Variations in MAP and flow continuity were expressed by the coefficient of variation; analysis of variance was used for comparisons. RESULTS: The mean coefficients of variations for MAP varied from 3.8 +/- 3.1% (linear piston/syringe) to 6.1 +/- 6.6% (linear peristaltic), and from 3.4 +/- 2.2% (10 mL/hr) to 7.9 +/- 6.6% (1 mL/hr). The coefficients of variation for in vitro flow continuity ranged from 9 +/- 8% (linear piston-syringe) to 250 +/- 162% (pulsatile diaphragm), and from 35 +/- 44% (10 mL/hr) to 138 +/- 196% (1 mL/hr). Both the type of pump and infusion rate significantly (p < .001) influenced variation in drug delivery rate. The 1 mL/hr infusion rate significantly (p < .01) influenced MAP variation. Cyclic fluctuations in MAP of < or = 30 mm Hg were observed using the pulsatile diaphragm pump at 1 mL/hr. CONCLUSION: Factors inherent in the operating mechanisms of infusion pumps may result in clinically important hemodynamic fluctuations when administering a concentrated short-acting vasoactive medication at slow infusion rates.

Uterine stromal sarcoma cell line. A cytogenetic and electron microscopic study.

Uterine sarcomas constitute approximately 3% of all malignant uterine corpus tumors. Of these, the tumors that originate solely in the stromal elements of the uterine wall are relatively infrequent and have not been well characterized cytogenetically. We report data from a low-grade endometrial stromal sarcoma both at the time of resection and after months in long-term tissue culture. Cytogenetic analysis showed a clonal population of cells with an abnormal karyotype of 46,XX,del(5)(q31.1),der(7)t(6;7)(p21;p22) which remained unchanged in long-term culture. Electron microscopy suggests that these cells are similar to other neoplastic cells in having immature-appearing nuclei surrounded by a relatively mature cytoplasm (with well-developed organelles). Determination of the specificity of these observations must await study of additional stromal sarcomas.

Biogeochemical processes governing exposure and uptake of organic pollutant compounds in aquatic organisms.

This paper reviews current knowledge of biogeochemical cycles of pollutant organic chemicals in aquatic ecosystems with a focus on coastal ecosystems. There is a bias toward discussing chemical and geochemical aspects of biogeochemical cycles and an emphasis on hydrophobic organic compounds such as polynuclear aromatic hydrocarbons, polychlorinated biphenyls, and chlorinated organic compounds used as pesticides. The complexity of mixtures of pollutant organic compounds, their various modes of entering ecosystems, and their physical chemical forms are discussed. Important factors that influence bioavailability and disposition (e.g., organism-water partitioning, uptake via food, food web transfer) are reviewed. These factors include solubilities of chemicals; partitioning of chemicals between solid surfaces, colloids, and soluble phases; variables rates of sorption, desorption; and physiological status of organism. It appears that more emphasis on considering food as a source of uptake and bioaccumulation is important in benthic and epibenthic ecosystems when sediment-associated pollutants are a significant source of input to an aquatic ecosystem. Progress with mathematical models for exposure and uptake of contaminant chemicals is discussed briefly.

DNA attachment to the hamster sperm nuclear matrix and nuclear annulus.

Hamster sperm DNA is packaged so tightly that it is the most highly condensed eukaryotic DNA known. Nevertheless, the sperm genome is also organized in a very specific fashion by two nuclear structures, the nuclear matrix and the nuclear annulus. The nuclear matrix organizes sperm DNA into loop domains approximately 46 Kb in length by specific attachment sequences. When the sperm nucleus is induced to decondense, the nuclear matrix almost completely dissipates, leaving only the nuclear annulus, a structure located at the implantation fossa within the nucleus. All the DNA remains anchored to the annulus during decondensation. Rotary shadowing transmission electron microscopy of isolated nuclear annuli retaining only a small portion of this anchored DNA suggests that the DNA is anchored to the annulus in a series of mini-loops, 5-10 Kb in length. These data support our previous suggestions that sperm DNA is organized in a very specific manner.