Relating Physiologic Swallowing Impairment, Functional Swallowing Ability, and Swallow-Specific Quality of Life.

Many studies include functional swallowing ability and quality of life information to indicate a response to a specific swallowing intervention or to describe the natural history of dysphagia across diseases and conditions. Study results are difficult to interpret because the association between these factors and actual swallowing impairment is not understood. We set out to test the associations between components of physiologic swallowing impairment, functional swallowing ability, and swallow-specific quality of life using standardized and validated measurement tools: Modified Barium Swallow Impairment Profile (MBSImP), Functional Oral Intake Scale (FOIS), Eating Assessment Tool (EAT-10), and Dysphagia Handicap Index (DHI). We specifically aimed to understand which factors may contribute to the overall relationships between these measurement tools when analyzed using total scores and item-level scores. This study included a heterogeneous cohort of 273 outpatients who underwent a modified barium swallow study (MBSS). We found significant correlations between MBSImP total scores and FOIS scores and DHI total scores, but not between MBSImP total scores and EAT-10 total scores. Significant correlations were also found between MBSImP item-level component scores and FOIS scores, EAT-10 total scores, and DHI total scores. Detailed item-level analyses revealed the MBSImP components of bolus transport/lingual motion, oral residue, and tongue base retraction were correlated with EAT-10 item-level scores and DHI item-level scores. The clinically modest associations between physiologic swallowing impairment, functional swallowing ability, and swallow-specific quality of life reveal different factors that uniquely contribute to patients' overall dysphagic profile, emphasizing the clinical impact of a comprehensive swallowing assessment.

Construct validity of the Eating Assessment Tool (EAT-10).

PURPOSE: We aimed to evaluate the construct validity of the Eating Assessment Tool (EAT-10) by determining its dimensionality, rating scale integrity, item-person match, precision and relationship with the degree of airway invasion and functional oral intake. METHODS: We conducted a retrospective analysis of patients' EAT-10 scores. We used the Rasch rating scale model. We investigated correlations between the EAT-10 and scores on the Penetration-Aspiration Scale (PAS) and Functional Oral Intake Scale (FOIS). RESULTS: The median score of the EAT-10 from 127 patients was 16 of 40 (range 0-40). Confirmatory factor analysis supported unidimensionality. The 5-point rating scale categories met published criteria. Two items misfit the Rasch model and two other items displayed differential item functioning. Rasch person reliability was 0.79. Our patient cohort was divided into three person-strata. Correlations between the EAT-10 and the PAS and FOIS were weak to moderate in strength (respectively: r = 0.26, p = 0.0036; r = -0.27, p = 0.0027). CONCLUSIONS: Our analyses identified deficits in the construct validity of the EAT-10 suggestive of a need to improve the EAT-10 to support its frequent use in clinical practice and research. Implications for Rehabilitation Swallowing disorders are associated with severe complications, such as pneumonia and malnutrition, and impose both social and psychological burdens on patients. The Eating Assessment Tool is a self-report instrument developed to estimate initial dysphagia severity and monitor change in patient-reported dysphagia symptoms as a response to treatment. This study shows that the Eating Assessment Tool has deficits in its construct validity and a need to improve the instrument to support its frequent use in clinical practice and research.

Identification of Swallowing Tasks From a Modified Barium Swallow Study That Optimize the Detection of Physiological Impairment.

Purpose: The purpose of this study was to identify which swallowing task(s) yielded the worst performance during a standardized modified barium swallow study (MBSS) in order to optimize the detection of swallowing impairment. Method: This secondary data analysis of adult MBSSs estimated the probability of each swallowing task yielding the derived Modified Barium Swallow Impairment Profile (MBSImP™©; Martin-Harris et al., 2008) Overall Impression (OI; worst) scores using generalized estimating equations. The range of probabilities across swallowing tasks was calculated to discern which swallowing task(s) yielded the worst performance. Results: Large-volume, thin-liquid swallowing tasks had the highest probabilities of yielding the OI scores for oral containment and airway protection. The cookie swallowing task was most likely to yield OI scores for oral clearance. Several swallowing tasks had nearly equal probabilities (≤ .20) of yielding the OI score. Conclusions: The MBSS must represent impairment while requiring boluses that challenge the swallowing system. No single swallowing task had a sufficiently high probability to yield the identification of the worst score for each physiological component. Omission of swallowing tasks will likely fail to capture the most severe impairment for physiological components critical for safe and efficient swallowing. Results provide further support for standardized, well-tested protocols during MBSS.

Crime scene analysis and the escalation of violence in serial rape.

The current study examines the crime scene behavior manifest by 108 serial rapists responsible for the perpetration of 565 rapes across various cities within the US. The goal of the current study is to identify which aspects of crime scene behavior reported to law enforcement by the victim are most useful in predicting, early in a series of offenses, which rapists are most likely to escalate into higher and, at times, life threatening levels of violence. Using 58 scales that quantify the verbal, physical, and sexual behavior manifest by a rapist in his interaction with his victim during his first reported rape and 36 modal variables that summarized approach, timing, demographics, and weapon usage across the series of rapes, the study attempts to differentiate between those rapists who escalate in their use of blunt force (Increasers) from those who do not (Non-Increasers). A logistic regression indicates that rapists who are white rather than of minority status and who, at the time of their first reported rape, rape their victims for longer periods of time and use more profanity are more likely to escalate in their level of blunt force than those rapists who do not exhibit these behaviors. The relevance of this type of predictive framework for law enforcement in its attempts to prioritize particular investigations is discussed.

The sexually sadistic serial killer.

This article explores characteristics and crime scene behavior of 20 sexually sadistic serial murderers. The pairing of character pathology with paraphilic arousal to the control and degradation of others is examined as it manifests itself in their murders. Commonalities across murders and across murderers are highlighted, i.e., the execution of murders that are well-planned, the use of preselected locations, captivity, a variety of painful sexual acts, sexual bondage, intentional torture, and death by means of strangulation and stabbing.

The effects of a novel and selective inhibitor of tryptophan 2,3-dioxygenase on tryptophan and serotonin metabolism in the rat.

The effects of a novel inhibitor 680C91 ((E)-6-fluoro-3-[2-(3- pyridyl)vinyl]-1H-indole) of the key enzyme of tryptophan catabolism tryptophan 2,3-dioxygenase (TDO) (EC 1.13.11.11), were examined on tryptophan catabolism in vitro and in vivo and on brain levels of tryptophan, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA). 680C91 was a potent (Ki = 51 nM) and selective TDO inhibitor with no inhibitory activity against indoleamine 2,3-dioxygenase (EC 1.13.11.17), monoamine oxidase A and B, 5-HT uptake and 5-HT1A,1D,2A and 2C receptors at a concentration of 10 microM. 680C91 had no effect on the binding of tryptophan to serum albumin in plasma and inhibited TDO competitively with respect to its substrate tryptophan. 680C91 inhibited the catabolism of tryptophan by rat liver cells and rat liver perfused in situ. The catabolism of L-[ring-2-14C]-tryptophan and a load dose of tryptophan (100 mg/kg) in vivo were inhibited by prior administration of 680C91. Administration of 680C91 alone produced marked increases in brain tryptophan, 5-HT and 5-HIAA. A load dose of tryptophan (100 mg/kg), producing increases in brain tryptophan 4-fold greater than that seen with 680C91, did not increase brain 5-HT and 5-HIAA to levels greater than those seen with 680C91 and produced a shorter-lasting increase in these parameters. These data therefore demonstrate the importance of TDO as a regulator of whole-body tryptophan catabolism and brain levels of tryptophan and 5-HT and suggest that a greater antidepressant efficacy might be achieved with inhibitors of TDO than tryptophan administration alone.

Determination of brain nitric oxide synthase inhibition in vivo: ex vivo assays of nitric oxide synthase can give incorrect results.

The in vivo potencies of N omega-nitro-L-arginine (L-NA), N omega-monomethyl-L-arginine (L-NMMA) and N omega-iminoethyl-L-ornithine (L-NIO) against brain nitric oxide synthase (NOS) were determined by assessing their ability to inhibit harmaline-induced increases in rat cerebellar cGMP. L-NA, L-NIO and L-NMMA were all able to completely prevent the harmaline-induced increase in cGMP with ID50s of 0.5, 30 and 55 mg/kg, respectively, and with the same order of potency as that seen for inhibition of cerebellar NOS in vitro. The inhibitory effects of low doses of L-NA on cerebellar cGMP were maintained for at least 8 hr. The ID50 of L-NA for inhibition of cerebellar cGMP in vivo was similar to its ID50 for inhibition of cerebellar NOS ex vivo but only when NOS activity was assayed as an initial rate. However, doses of L-NMMA and L-NIO that inhibited harmaline-induced increases in cerebellar cGMP in vivo by 50% failed to inhibit NOS ex vivo. The methyl ester of L-NA, L-NAME, produced substantial inhibition of cerebellar NOS ex vivo when given either orally, intraperitoneally or intravenously but with a slower onset of action than L-NA. These results demonstrate that measurement of NOS activity ex vivo can accurately reflect the degree of inhibition of NOS in vivo with inhibitors that dissociate slowly from the enzyme such as L-NA, but only when the initial rate of NOS activity is measured.

The effects of an inhibitor of tryptophan 2,3-dioxygenase and a combined inhibitor of tryptophan 2,3-dioxygenase and 5-HT reuptake in the rat.

The effects of a novel inhibitor 680C91 ((E)-6-fluoro-3-[2-(3-pyridyl)vinyl]-1H-indole) of the key enzyme of tryptophan catabolism tryptophan 2,3-dioxygenase (TDO), and a novel inhibitor 709W92 ((E)-6-fluoro-3-[2-(4-pyridyl)vinyl]-1H-indole), of both TDO and 5-hydroxytryptamine (5-HT) reuptake, were examined on tryptophan catabolism, cerebrospinal fluid (CSF) concentrations of tryptophan and 5-HT and serotonergic-mediated physiology and behaviour in the rat. The catabolism of L-[ring-2-14C]tryptophan in vivo was completely inhibited by prior administration of 709W92. 709W92, but not 680C91, potentiated head-twitch produced by 5-hydroxytryptophan, prevented head-twitch and whole brain 5-HT depletion produced by p-chloroamphetamine and rapidly decreased dorsal raphe firing. Both 709W92 and 680C91 elevated CSF tryptophan by up to 260% of basal concentration. A maximally effective dose of 680C91 elevated a global measure of brain extracellular 5-HT (CSF 5-HT) to concentrations similar to those seen maximally after exogenous tryptophan administration (approx 170% of basal). Maximally effective doses of 709W92 increased CSF 5-HT to concentrations comparable to those seen after tryptophan and 5-HT reuptake inhibitor coadministration (approx 900% of basal) and to concentrations greater than those achieved maximally with serotonergically active antidepressant monotherapy (approx 500% of basal). 709W92 did not elevate CSF 5-HT to concentrations associated with the serotonin syndrome (approx 3000% of basal). The combined TDO inhibitor/5-HT reuptake inhibitor, 709W92, showed anxiolytic activity in the rat-pup vocalization model of anxiety. These results show that 709W92 (a novel inhibitor of both TDO and 5-HT reuptake), can produce an elevation of CSF 5-HT similar to that achieved with a serotonin reuptake inhibitor/tryptophan combination therapy but with a more sustained timecourse; such compounds may therefore have superior antidepressant efficacy in the clinic.

Potent and selective inhibition of human nitric oxide synthases. Selective inhibition of neuronal nitric oxide synthase by S-methyl-L-thiocitrulline and S-ethyl-L-thiocitrulline.

Potent and selective inhibition of neuronal nitric oxide synthase (nNOS) compared to endothelial NOS (eNOS) and inducible NOS (iNOS) may be useful to treat cerebral ischemia (stroke) and other neurodegenerative diseases. S-Methyl-L-thiocitrulline (Me-TC) and S-ethyl-L-thiocitrulline (Et-TC) inhibited the oxidation of L-arginine and the L-arginine-independent oxidation of NADPH by nNOS from human brain. Me-TC and Et-TC were slow, tight binding inhibitors of nNOS with second-order association rate constants (kon) of 2.6 x 10(5) M-1 s-1 and 1.3 x 10(5) M-1 s-1, respectively. The respective dissociation rate constants (koff) were 3 x 10(-4) s-1 and 0.7 x 10(-4) s-1. Thus, the Kd values calculated from koff/kon were 1.2 and 0.5 nM, respectively. L-Arginine was a competitive inhibitor of Me-TC and Et-TC binding with competition constant (Ks) values of 2.2 and 2.7 microM, respectively. The Km of nNOS for L-arginine was 1.6 microM. The active site concentration of nNOS was estimated by titration with Et-TC. Based on this active site concentration, a kcat of 0.4 s-1 for the oxidation of L-arginine, was calculated. Me-TC and Et-TC were less potent inhibitors of human iNOS (Ki values of 34 and 17 nM, respectively) and human eNOS (Ki values of 11 and 24 nM). Thus, Me-TC and Et-TC were 10- and 50-fold, respectively, more potent inhibitors of nNOS than eNOS. Furthermore, Me-TC was also 17-fold selective for rat nNOS in neuronal tissue compared to rat eNOS in vascular endothelium, suggesting that Me-TC may be selective for nNOS in vivo and therefore, may be therapeutically useful to treat neurodegenerative diseases.

Effects of diabetes mellitus on lactation in the rat.

Diabetes mellitus adversely affects the process of lactation. Although insulin administration restores lactation, the manner by which it does so is unknown. The goals of this study were to determine which phase of lactation, milk synthesis/supply (MS), and/or milk release (MR) was affected. Inasmuch as insulin, corticosterone, and prolactin, among other hormones, are involved in milk synthesis in vitro, this study investigated their probable roles in the suppression of lactation in diabetes in vivo. Diabetes was induced in rats on Day 3 postpartum with streptozotocin (50-60 mg/kg, ip). Milk synthesis/supply and milk release were indirectly monitored using body weight gain of pups during a timed-feeding period on postnatal Days 8/9 and 13/14. Plasma corticosterone, insulin, C-peptide, and prolactin were measured by radioimmunoassay in control, diabetic, and insulin-replaced diabetic animals. Insulin replacement was provided by means of an osmotic minipump implanted subcutaneously in the nape of the neck. In addition, several parameters of maternal behavior were monitored in order to determine whether diabetes affected maternal behavior and, therefore, whether such changes played a role in the alterations of lactation observed during diabetes. Diabetes significantly suppressed MS and MR. However, the decrease in MR, which was restored after partial insulin replacement, was a reflection of the reduced MS. There were no significant differences between the parameters of maternal behavior monitored in control and diabetic animals. Blood glucose in diabetic dams was significantly increased over that of controls. Although the levels of plasma glucose in the insulin-replaced groups were significantly lower than those of their uncontrolled diabetic counterparts, they also remained higher than that of controls. Corticosterone was not significantly altered after induction of diabetes. Insulin and C-peptide levels were significantly reduced in the uncontrolled diabetics; however, insulin levels were corrected in the insulin-replaced groups. Serum levels of prolactin decreased in all diabetic groups and insulin failed to restore these levels to those of control animals. In conclusion, it appears that diabetes decreases lactation through a suppressive effect on MS rather than on MR, with insulin replacement correcting for such deficiency. In addition, despite the lactogenic importance of glucocorticoids, prolactin and insulin demonstrated in vitro, lactation in vivo can be corrected without returning the levels of all three hormones to normal. The importance of another factor(s), such as normoglycemia, as essential to the observed defects, needs to be investigated.

Compliant victims of the sexual sadist.

This is a descriptive summary of the experiences of a sample of women who have been consensually involved with criminal sexual sadists. The paper details the physical, sexual, and psychological abuse to which the women were subject as well as the process by which they were transformed from independent, competent women to the compliant appendages of their criminally active partners. Similarities in the sexual sadist's criminal and consensual sexual activities as they reflect a specific paraphilic preference are discussed.

Fatal and near-fatal autoerotic asphyxial episodes in women. Characteristic features based on a review of nine cases.

As asphyxial episodes during autoerotic activity are rarely reported in women, a review of eight fatal cases and one near-fatal case was conducted to delineate more clearly the characteristics of this syndrome in women. Six cases involved characteristic fatal autoerotic asphyxial activity. The remaining two fatal cases were atypical in that the apparatus that was used for sexual purposes was not intended to cause asphyxia in one case and did not directly cause asphyxial death in the second case. The final case was not fatal. Significantly, the majority of women did not use unusual clothing, props, or devices to augment their activity, for example, five were completely naked and only one was found with elaborate clothing and extra ligatures. Six of the fatal cases had objective evidence of sexual activity, three had used neck padding to prevent chafing, and eight had failed self-rescue mechanisms. Of note, the initial impression in four cases (44%) was homicide (two), attempted suicide (one), and accidental death during sexual activity with a partner (one). These results support the assertion that the manifestations of female autoerotic asphyxial activity reported to date may be initially misleading to investigators. Our purpose in presenting these findings, therefore, is to increase awareness of the more subtle features of this syndrome in women in an attempt to reduce the potential for underdiagnosis or confusion with nonaccidental death in future cases.

The effect of C-terminus and N-terminus iodination on avian pancreatic polypeptide (APP) binding to its chicken brain receptor.

In previous studies, membranes from chicken gastrointestinal tissues failed to bind appreciable levels of 125I-APP labeled at the C-terminus. In order to address the suggestion that this was due to steric hindrance of the critical C-terminus, N-terminally labeled 125I-APP was utilized in in vitro membrane binding assays. Membranes from chicken cerebellum and spleen specifically bound N-terminally iodinated APP, while those from gastrointestinal tissues including pancreas, mucosal and muscle layers of duodenum and proventriculus did not. Cerebral cortex membranes also failed to specifically bind Bolton-Hunter labeled 125I-APP. Liver membranes, which previously were shown to bind C-terminally iodinated APP with low affinity, also did not specifically bind N-terminally labeled preparations. It is concluded that the inability of membranes from gastrointestinal tissues and brain regions other than cerebellum to bind 125I-APP is not an artifact of location of iodine placement on the molecule and that both the N- and C-termini may be important for receptor binding. It is also concluded that liver APP binding sites may be structurally distinct from those in the cerebellum, and that gastrointestinal tissues may not be direct targets for APP action.

Specific neuropeptide Y binding sites in chicken brain.

In the present study, 125I-labeled neuropeptide Y (NPY) binding to chicken brain regions was evaluated. Cerebellum and cerebral cortex membranes bound significantly more 125I-NPY specifically than did membranes from other brain regions. Scatchard plots of NPY binding to cerebellar membranes were curvilinear; the high-affinity component had an affinity (Kd) of 1.1 nM, with a receptor concentration (Ro) of 182 fmol/mg membrane protein. Scatchard plots of NPY binding to chicken cerebral cortex membranes were linear, with a Kd of 0.63 nM and Ro of 90 fmol/mg. Unlabeled avian pancreatic polypeptide (APP) inhibited 125I-NPY binding to cerebellar membranes with a constant at which 50% inhibition occurs of 0.5 nM but showed essentially no affinity for cerebral cortex NPY binding sites. As previously reported, 125I-APP bound to cerebellar membranes with a Kd of 0.365 nM and an Ro of 323 fmol/mg, and unlabeled NPY showed about one order of magnitude lower affinity than did unlabeled APP for 125I-APP binding sites. Pseudo-Hill coefficients for APP binding to cerebellar APP receptors and NPY binding to cerebellar NPY receptors were 0.9. In contrast, pseudo-Hill plots for APP competition for 125I-NPY binding were curvilinear. It is concluded that the chicken cerebellum contains distinct APP and NPY receptors, whereas cerebral cortex contains only NPY receptors. APP is capable of binding with high affinity to the cerebellar, but not the cortical, NPY receptor.

A comparison of typical death scene features in cases of fatal male and autoerotic asphyxia with a review of the literature.

Autoerotic asphyxia is an increasingly recognised syndrome in which accidental death occurs during solitary sexual activity due to failure of an apparatus that was designed to produce hypoxic augmentation of the victim's sexual response. Evidence of repetitive, secretive behaviour utilizing ropes and ligatures characterizes cases involving either males or females. Here the similarity in reported cases ends with males tending to utilize a far greater range of elaborate devices and props, often designed to cause real or simulated pain with pornographic material and evidence of cross-dressing and fetishism. Females, on the other hand, have usually been found naked with only a single ligature and no unusual or bizarre equipment. To further clarify the similarities and differences between typical cases involving males and females and to assist in the diagnosis of less obvious cases, the literature is reviewed and characteristic findings in both sexes compared and contrasted.

The sexually sadistic criminal and his offenses.

This is an uncontrolled, descriptive study of 30 sexually sadistic criminals. All were men, and all intentionally tortured their victims in order to arouse themselves. Their crimes often involved careful planning, the selection of strangers as victims, approaching the victim under a pretext, participation of a partner, beating victims, restraining victims and holding them captive, sexual bondage, anal rape, forced fellatio, vaginal rape, foreign object penetration, telling victims to speak particular words in a degrading manner, murder or serial killings (most often by strangulation), concealing victims' corpses, recording offenses, and keeping personal items belonging to victims.

Characterization of liver and cerebellar binding sites for avian pancreatic polypeptide.

Microsomal membranes from chicken liver and cerebellum specifically bind 125I-labeled avian pancreatic polypeptide (APP) with widely different affinities. To understand further the structural basis for this affinity difference as well as to determine the nature of the PP receptor, certain biochemical characteristics of chicken cerebellar and liver membrane [125I] APP-binding sites were determined. Trypsin digestion markedly reduced liver and cerebellar membrane binding of [125I]APP. Neuraminidase did not alter binding, while phospholipase-C lowered liver specific [125I]APP binding via a nonspecific digestion of the membrane. Cerebellar [25I]APP binding was unaltered by phospholipase-C. Dithiothreitol significantly inhibited liver and cerebellar specific [125I]APP binding without altering affinity. N-Ethylmaleimide (NEM) potently inhibited specific cerebellar [125I]APP binding and affinity and increased liver [125I]APP binding without altering affinity. NEM inhibited [125I]APP degradation by both liver and cerebellar membranes. NEM caused significant dissociation of [125I]APP from cerebellar membranes. Collectively, these studies indicate that chicken liver and cerebellar membrane [125I]APP-binding sites (either the putative receptors per se or the surrounding membranes) are proteinaceous and possess disulfide bonds important in ligand binding. Free thiol groups appear essential for cerebellar [125I]APP binding, while in liver membranes, free thiol groups interfere with binding or play no role in the binding process per se. These studies provide a foundation for a more precise molecular definition of the structures of PP receptors.