The effects of incremental maxillomandibular advancement surgery on airway morphology: a cadaveric study.

Evidence demonstrates efficacy of maxillomandibular advancement (MMA) treatment of obstructive sleep apnea (OSA) and airway expansion. Patient studies are limited to pre/post-surgery comparisons. This cadaveric study evaluated intra-individual relationships between magnitudes of MMA advancement and airway changes. MMA with distraction osteogenesis devices and incremental advancement of the maxillomandibular complex, was performed on cadavers (n = 5). Computed tomography at each 2-mm advancement was used to measure volume and dimension of the oropharyngeal airway. Three-dimensional shape analysis visualized magnitudes and locations of changes. Incremental advancements caused volume, anteroposterior, and lateral dimensions to increase progressively, while length decreased. Changes were significant at lower advancements. Comparisons of MMA indicate alterations in airway volume from 4 to 6 mm and 6 to 8 mm were relatively greater than the changes from 8 to 10 mm (P = 0.044, P = 0.028, respectively), 10 to 12 mm (P = 0.024, P = 0.023), and 12 to 14 mm (P = 0.021, P = 0.019). These results may expand MMA application suggesting 6-8 mm advancements provide substantial increases in airway volume. MMA may be an OSA treatment option when large advancements are not possible. Lower magnitudes of advancement decrease risks of unfavorable facial esthetics from excess protrusion.

Effects of postural changes and removal of vestibular inputs on blood flow to and from the hindlimb of conscious felines.

Considerable data show that the vestibular system contributes to blood pressure regulation. Prior studies reported that lesions that eliminate inputs from the inner ears attenuate the vasoconstriction that ordinarily occurs in the hindlimbs of conscious cats during head-up rotations. These data led to the hypothesis that labyrinthine-deficient animals would experience considerable lower body blood pooling during head-up postural alterations. The present study tested this hypothesis by comparing blood flow though the femoral artery and vein of conscious cats during 20-60 degrees head-up tilts from the prone position before and after removal of vestibular inputs. In vestibular-intact animals, venous return from the hindlimb dropped considerably at the onset of head-up tilts and, at 5 s after the initiation of 60 degrees rotations, was 66% lower than when the animals were prone. However, after the animals were maintained in the head-up position for another 15 s, venous return was just 33% lower than before the tilt commenced. At the same time point, arterial inflow to the limb had decreased 32% from baseline, such that the decrease in blood flow out of the limb due to the force of gravity was precisely matched by a reduction in blood reaching the limb. After vestibular lesions, the decline in femoral artery blood flow that ordinarily occurs during head-up tilts was attenuated, such that more blood flowed into the leg. Contrary to expectations, in most animals, venous return was facilitated, such that no more blood accumulated in the hindlimb than when labyrinthine signals were present. These data show that peripheral blood pooling is unlikely to account for the fluctuations in blood pressure that can occur during postural changes of animals lacking inputs from the inner ear. Instead, alterations in total peripheral resistance following vestibular dysfunction could affect the regulation of blood pressure.

Effects of postural changes and removal of vestibular inputs on blood flow to the head of conscious felines.

Prior studies have shown that removal of vestibular inputs produces lability in blood pressure during orthostatic challenges (Holmes MJ, Cotter LA, Arendt HE, Cass SP, and Yates BJ. Brain Res 938: 62-72, 2002; Jian BJ, Cotter LA, Emanuel BA, Cass SP, and Yates BJ. J Appl Physiol 86: 1552-1560, 1999). Furthermore, these studies led to the prediction that the blood pressure instability results in susceptibility for orthostatic intolerance. The present experiments tested this hypothesis by recording common carotid blood flow (CCBF) in conscious cats during head-up tilts of 20, 40, and 60 degrees amplitudes, before and after the surgical elimination of labyrinthine inputs through a bilateral vestibular neurectomy. Before vestibular lesions in most animals, CCBF remained stable during head-up rotations. Unexpectedly, in five of six animals, the vestibular neurectomy resulted in a significant increase in baseline CCBF, particularly when the laboratory was illuminated; on average, basal blood flow measured when the animals were in the prone position was 41 +/- 17 (SE) % higher after the first week after the lesions. As a result, even when posturally related lability in CCBF occurred after removal of vestibular inputs, blood supply to the head was not lower than when labyrinthine inputs were present. These data suggest that vestibular influences on cardiovascular regulation are more complex than previously appreciated, because labyrinthine signals appear to participate in setting basal rates of blood flow to the head in addition to triggering dynamic changes in the circulation to compensate for orthostatic challenges.

Mental contamination and mental correction: unwanted influences on judgments and evaluations.

We define mental contamination as the process whereby a person has an unwanted response because of mental processing that is unconscious or uncontrollable. This type of bias is distinguishable from the failure to know or apply normative rules of inference and can be further divided into the unwanted consequences of automatic processing and source confusion, which is the confusion of 2 or more causes of a response. Mental contamination is difficult to avoid because it results from both fundamental properties of human cognition (e.g., a lack of awareness of mental processes) and faulty lay beliefs about the mind (e.g., incorrect theories about mental biases). People's lay beliefs determine the steps they take (or fail to take) to correct their judgments and thus are an important but neglected source of biased responses. Strategies for avoiding contamination, such as controlling one's exposure to biasing information, are discussed.

A model of dual attitudes.

When an attitude changes from A1 to A2, what happens to A1? Most theories assume, at least implicitly, that the new attitude replaces the former one. The authors argue that a new attitude can override, but not replace, the old one, resulting in dual attitudes. Dual attitudes are defined as different evaluations of the same attitude object: an automatic, implicit attitude and an explicit attitude. The attitude that people endorse depends on whether they have the cognitive capacity to retrieve the explicit attitude and whether this overrides their implicit attitude. A number of literatures consistent with these hypotheses are reviewed, and the implications of the dual-attitude model for attitude theory and measurement are discussed. For example, by including only explicit measures, previous studies may have exaggerated the ease with which people change their attitudes. Even if an explicit attitude changes, an implicit attitude can remain the same.

Collisionally activated dissociations of aminocyclitol-aminoglycoside antibiotics and their application in the identification of a new compound in tobramycin samples.

Several aminocyclitol-aminoglycoside antibiotics have been studied by tandem mass spectrometry. Glycosidic bond cleavages were the major reactions in the low energy collisionally activated decomposition (CAD) of the protonated antibiotics. Only the glycoside residing on the C6-O of the 2-deoxystreptamine was observed to undergo significant decomposition at the C2-C3 and O-C1 bonds. The comprehension of the CAD of known aminoglycosides aided in the identification of an unknown impurity in tobramycin. The unknown compound was initially detected by reverse phase high-performance liquid chromatography following dinitrofluorobenzene derivatization of the amino groups. The molecular weight of the dinitrobenzene derivative measured by LC mass spectrometry (MS) led to the detection of two isomeric impurities in tobramycin by LC-MS using an amino column. Their CAD spectra were subsequently acquired by LC-MS/MS. One of the two compounds was determined to be a known compound, 6"-O-carbamyltobramycin with the carbamyl group substituted on the glycoside residing on the C6-O of 2-deoxystreptamine. The fragmentation pattern of the other compound was interpreted as that the unknown was also a carbamyltobramycin. The carbamyl group was, however, substituted on 2-deoxystreptamine. It was speculated that the carbamyl group was substituted at the C1 amino group. This compound, to our knowledge, has not been reported before.

A new look at anchoring effects: basic anchoring and its antecedents.

In previous anchoring studies people were asked to consider an anchor as a possible answer to the target question or were given informative anchors. The authors predicted that basic anchoring effects can occur, whereby uninformative numerical anchors influence a judgment even when people are not asked to compare this number to the target value. Five studies supported these hypotheses: Basic anchoring occurs if people pay sufficient attention to the anchor value; knowledgeable people are less susceptible to basic anchoring effects; anchoring appears to operate unintentionally and nonconsciously in that it is difficult to avoid even when people are forewarned. The possible mechanisms of basic anchoring and the relation between these mechanisms and other processes of judgment and correction are discussed.

Thinking too much: introspection can reduce the quality of preferences and decisions.

In Study 1, college students' preferences for different brands of strawberry jams were compared with experts' ratings of the jams. Students who analyzed why they felt the way they did agreed less with the experts than students who did not. In Study 2, college students' preferences for college courses were compared with expert opinion. Some students were asked to analyze reasons; others were asked to evaluate all attributes of all courses. Both kinds of introspection caused people to make choices that, compared with control subjects', corresponded less with expert opinion. Analyzing reasons can focus people's attention on nonoptimal criteria, causing them to base their subsequent choices on these criteria. Evaluating multiple attributes can moderate people's judgments, causing them to discriminate less between the different alternatives.

Knowing what you'll do: effects of analyzing reasons on self-prediction.

Analyzing the reasons why one would or would not act in a certain way was predicted to increase the perceived likelihood of the behavior and to lower the accuracy of the self-predictions. In 3 studies, college students predicted whether they would act in friendly or unfriendly ways toward an acquaintance. Those asked to analyze reasons why they would or would not perform the behaviors, as compared with no-analyze controls, were more likely to say they would perform the behaviors, showing a confirmation bias; made less accurate predictions, because analyzing reasons changed their predictions but not their actual behavior; and were more overconfident, because analyzing reasons lowered accuracy but not confidence. Each of these effects was especially pronounced when people's initial liking for the target person was different from the valence of the behavior they were predicting.

Preferences as expectation-driven inferences: effects of affective expectations on affective experience.

Presents a model arguing that affect and emotion are often formed in an expectation-driven fashion. A pilot study and 2 experiments manipulated undergraduate Ss' affective expectations (e.g., how funny they expected a set of cartoons to be) and whether Ss' expectations were confirmed (e.g., whether the cartoons really were funny). When the value of a stimulus was consistent with an affective expectation, people formed evaluations relatively quickly. Even when the value of a stimulus was discrepant from an affective expectation, people sometimes assimilated the value of the stimulus to their expectations. Other times, such as when making a more fine-grained evaluation of the cartoons, people noticed that they were discrepant from their affective expectations. Under these conditions, people appeared to have more difficulty forming preferences. They took longer to evaluate and spent more time thinking about the cartoons.

Effects of introspecting about reasons: inferring attitudes from accessible thoughts.

Previous research has shown that analyzing reasons can change people's attitudes, but the exact mechanisms of this effect have not been entirely clear. It was hypothesized that introspecting about reasons focuses people's attention on thoughts that are accessible in memory and increases the extent to which people view their accessible thoughts as applicable to their current attitudes. In Study 1, college students formed initial impressions of a target person, and then positive or negative thoughts about the target person were made memorable. After a delay, half of the participants analyzed reasons for their attitude and half recalled the target person's behaviors. As predicted, people who analyzed reasons reported attitudes toward the target person that were based more on what they could recall about her. Study 2 showed that this effect occurs regardless of whether people initially form an online impression. Implications for the effects of analyzing reasons and for attitude formation are discussed.

Immune neglect: a source of durability bias in affective forecasting.

People are generally unaware of the operation of the system of cognitive mechanisms that ameliorate their experience of negative affect (the psychological immune system), and thus they tend to overestimate the duration of their affective reactions to negative events. This tendency was demonstrated in 6 studies in which participants overestimated the duration of their affective reactions to the dissolution of a romantic relationship, the failure to achieve tenure, an electoral defeat, negative personality feedback, an account of a child's death, and rejection by a prospective employer. Participants failed to distinguish between situations in which their psychological immune systems would and would not be likely to operate and mistakenly predicted overly and equally enduring affective reactions in both instances. The present experiments suggest that people neglect the psychological immune system when making affective forecasts.

Focalism: a source of durability bias in affective forecasting.

The durability bias, the tendency to overpredict the duration of affective reactions to future events, may be due in part to focalism, whereby people focus too much on the event in question and not enough on the consequences of other future events. If so, asking people to think about other future activities should reduce the durability bias. In Studies 1-3, college football fans were less likely to overpredict how long the outcome of a football game would influence their happiness if they first thought about how much time they would spend on other future activities. Studies 4 and 5 ruled out alternative explanations and found evidence for a distraction interpretation, that people who think about future events moderate their forecasts because they believe that these events will reduce thinking about the focal event. The authors discuss the implications of focalism for other literatures, such as the planning fallacy.

The illusion of external agency.

People typically underestimate their capacity to generate satisfaction with future outcomes. When people experience such self-generated satisfaction, they may mistakenly conclude that it was caused by an influential, insightful, and benevolent external agent. In three laboratory experiments, participants who were allowed to generate satisfaction with their outcomes were especially likely to conclude that an external agent had subliminally influenced their choice of partners (Study 1), had insight into their musical preferences (Study 2), and had benevolent intentions when giving them a stuffed animal (Study 3). These results suggest that belief in omniscient, omnipotent, and benevolent external agents, such as God, may derive in part from people's failure to recognize that they have generated their own satisfaction.

High-performance liquid chromatographic determination of hydrocortisone cypionate: method development and characterization of chromatographic behavior.

A reversed-phase high-performance liquid chromatographic method for hydrocortisone cypionate bulk drug and oral solution was developed that avoids the use of a heated column as described in USP XX. A study of the effect of the organic modifier concentration on the capacity factor suggests that mixed partition and adsorption phenomena are responsible for the retention of several steroids when acetonitrile is used in the mobile phase. Evidence is presented that hydrogen bonding of the solute molecule with silane hydroxyl groups may be responsible for the adsorption.

Calorimetric studies of dissolution of hydroxypropyl methylcellulose E5 (HPMC E5) in water.

The interaction of water with polymers is important because it directly or indirectly affects various properties such as rheological and transport properties. In this study, the hydration/dissolution of a hydrophilic polymer was investigated by calorimetric techniques. Hydroxypropyl methylcellulose E5 (Methocel, HPMC E5) was used as the model polymer. A water-insoluble, hydrophobic polymer, ethyl cellulose E4 (Ethocel, EC E4), was selected for comparison. The number of moles of non-freezing and freezing water were determined by differential scanning calorimetry. Moles of non-freezing water per polymer repeat unit were 6.2 +/- 1.3 and 1.6 +/- 0.3 for HPMC E5 and EC E4, respectively. The hydration/dissolution of HPMC E5 was exothermic, with a total heat of dissolution of -24.1 +/- 1.1 cal/g (n = 4). The heat of hydration of water-insoluble EC E4 was -2.6 cal/g (n = 2). The specific heat capacity value of HPMC E5 increased due to the addition of water. The heat of solution and an increase in specific heat capacity values were associated mainly with the addition of tightly bound water to the polymer. The dissolution of HPMC E5 in water is believed to have endothermic and exothermic components. In summary, the study provided insight into the dissolution of a representative hydrophilic polymer in water. The heat of solution and the specific heat capacity values were mainly dependent on the addition of tightly bound water.

Simultaneous liquid chromatographic determination of glutaric acid, phenylephrine, and benzyl alcohol in a prototype nasal spray with application to di- and tricarboxylic acids.

A rapid reversed-phase high-performance liquid chromatographic method for the simultaneous determination of glutaric acid, phenylephrine, and benzyl alcohol in nasal spray has been developed. UV detection was utilized at 210 nm for the assay of glutaric acid and phenylephrine with an adjustment to 254 nm for the measurement of benzyl alcohol. Linearity and recovery data were obtained for each component in spiked placebo studies. An investigation of the retention mechanisms of the three components showed that phenylephrine was retained by ion-pairing with octanesulfonate anion while glutaric acid and benzyl alcohol partitioned as a suppressed ion and a neutral molecule, respectively. The method has been further extended to the reversed-phase separation of di- and tricarboxylic acids using a totally aqueous 0.0074 M phosphoric acid mobile phase. The retention of these acids was related to their octanol-water partition coefficients and structural variation.

A modified HET-CAM assay approach to the assessment of anti-irritant properties of plant extracts.

Hen's egg--chorioallantoic membranes were used to screen for and assess anti-irritant properties among aqueous extracts of plants (HET-CAM tests), in connection with searches for plant-derived substances with topical anti-irritant action. The main question to be answered was whether CAM-assay screening of plant extracts could provide a useful route to identifying promising anti-irritant extracts for follow-up clinical testing. To be useful, the method would have to flag materials with strong anti-irritant properties, and would have to avoid registering false negatives. The tests conducted provided positive indications. We measured the delays in onset of three manifestations of membrane irritation-vascular hemorrhaging, membrane lysis and membrane coagulation-observed with test substances relative to positive controls. Aqueous 15% lactic acid, a commonly used irritant in direct tests on human skin, was employed as the test irritant in this study. The ratio [irritation onset times after test substance pre-treatment]:[onset times without test substance pretreatment] was used to measure the anti-irritant power of test substances. A scoring notation was devised for this which treats the delay parameters as independent effects. Most tested plant extracts showed no significant irritant or anti-irritant effects. Among the apparently anti-irritant plant extracts (approx. 10% of all those tested), most showed their greatest effect against hemorrhaging. Lesser but still readily measurable effects against membrane lysis and coagulation were also observed in nearly all the apparently anti-irritant extracts. Two of the tested extracts proved to be membrane irritants. Some key CAM assay results were compared with results obtained in direct tests on human skin using the same test irritant (15% lactic acid). In these comparative tests on skin, an essentially similar pattern of efficacy was obtained, with the plant extract deemed best in the CAM screenings, outperforming the benchmark anti-irritant hydrocortisone. From these initial results it appears that physiological CAM assays may prove useful in screening natural materials for anti-irritant properties, as alternatives to mechanism-dependent biochemical assays, or expensive direct screening tests on human subjects. Further work remains to extend the CAM screening approach to irritants other than lactic acid, and to assess its quantitative powers of prediction of topical anti-irritancy.

Liquid chromatographic methods validation for pharmaceutical products.

The current status of validation in LC methods for the analysis of pharmaceuticals has been reviewed with special reference to compatibility testing methods. Validation data were provided in terms of method linearity, accuracy, precision, system suitability, specificity, use of alternate methods, injection order, application of peak height or area measurements and of internal or external standards.

Calorimetric evaluation of hydration of cholestyramine.

We have investigated the mechanism of hydration of cholestyramine, a water-insoluble resin used pharmaceutically. Two types of water of hydration (freezing and non-freezing) and the amounts of heat evolved or absorbed during the hydration of cholestyramine were determined. From differential scanning calorimetry, 0.57 g water was observed to be tightly bound per gram of resin (non-freezing water). The hydration of dry cholestyramine was found to be exothermic. The heats of hydration of cholestyramine with chloride or nitrate counter-anions were found to be -6.05 and -3.46 cal g-1, respectively. Some of the partially hydrated cholestyramine samples showed absorption of heat during hydration. The data generated in the study were utilized to better understand the mechanism of hydration and swelling of cholestyramine.