Lessons learned from the development of a hidradenitis suppurativa xenograft mouse model.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease originating from the pilosebaceous unit, in which patients develop painful abscesses, sinus tracts, nodules and scarring, typically in intertriginous areas. Major gaps in our understanding of HS exist, and these may be partially due to the lack of an animal model for experimental studies. We developed an HS xenograft mouse model using human HS lesions grafted onto immunocompromised mice. Although the model had its limitations, several informative lessons were learned, which may contribute to future attempts at an HS animal model.

Specimen Collection for Translational Studies in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by painful nodules, sinus tracts, and scars occurring predominantly in intertriginous regions. The prevalence of HS is currently 0.053-4%, with a predominance in African-American women and has been linked to low socioeconomic status. The majority of the reported literature is  retrospective, population based, epidemiologic studies. In this regard, there is a need to establish a repository of biospecimens, which represent appropriate gender and racial demographics amongst HS patients. These efforts will diminish knowledge gaps in understanding the disease pathophysiology. Hence, we sought to outline a step-by-step protocol detailing how we established our HS biobank to facilitate the formation of other HS tissue banks. Equipping researchers with carefully detailed processes for collection of HS specimens would accelerate the accumulation of well-organized human biological material. Over time, the scientific community will have access to a broad range of HS tissue biospecimens, ultimately leading to more rigorous basic and translational research. Moreover, an improved understanding of the pathophysiology is necessary for the discovery of novel therapies for this debilitating disease. We aim to provide high impact translational research methodology for cutaneous biology research and foster multidisciplinary collaboration and advancement of our understanding of cutaneous diseases.

Obesity increases the risk of small intestinal bacterial overgrowth (SIBO).

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) has been associated with anatomical and motility-related abnormalities. Specifically, obesity has been postulated to alter small bowel motility, leading to SIBO. AIMS: (i) Assess the prevalence of SIBO in obesity; (ii) determine the relationship of obesity and SIBO, using small bowel transit time (SBTT) and pH; (iii) profile the gut microbiome in obese and non-obese patients with SIBO. METHODS: Thirty consecutive participants referred for SIBO underwent lactulose breath tests (LBTs) and wireless motility capsule (WMC) studies. Composition of the intestinal microbiome was assessed by analyzing samples from three different gastrointestinal sites via 16S rRNA gene-sequencing. KEY RESULTS: SIBO was more frequent among obese patients vs non-obese patients (88.9% vs 42.9%, P < .05). Obesity did not correlate with small bowel transit time (SBTT), gastric pH, and small bowel pH. In patients with normal SBTT, obesity was associated with an 11-fold increase (P = .05) in the risk of SIBO. Whereas in those with prolonged SBTT, there was no correlation between obesity and SIBO. Obese vs non-obese patients exhibited significant differences in microbiome diversity in rectal samples. Obesity was associated with increased odds of developing SIBO (P = .04) in multivariate regression analyses. CONCLUSIONS AND INFERENCES: While obesity was significantly associated with SIBO, our findings suggest that alterations in gut pH, SBTT, and decline in species richness do not account for the obesity-SIBO relationship.

Nicotinic receptor subtypes mediating relaxation of the normal human clasp and sling fibers of the upper gastric sphincter.

BACKGROUND: Proper function of the gastro-esophageal high pressure zone is essential for the integrity of the antireflux barrier. Mechanisms include tonic contractions and the decreased tone during transient lower esophageal sphincter relaxations. METHODS: We characterized the pharmacology of nicotinic receptors mediating relaxations of the human upper gastric sphincter (clasp and sling fibers) using currently available subtype selective nicotinic antagonists in tissue from organ transplant donors. Donors with either a history of gastro-esophageal reflux disease or histologic evidence of Barrett's esophagus were excluded. Clasp and sling muscle fiber strips were used for one of three paradigms. For paradigm 1, each strip was exposed to carbachol, washed, exposed to nicotinic antagonists then re-exposed to carbachol. In paradigm 2, strips were exposed to a near maximally effective bethanechol concentration then nicotine was added. Strips then were washed, exposed to nicotinic antagonists then re-exposed to bethanechol followed by nicotine. In paradigm 3, strips were exposed to bethanechol then choline or cytisine. KEY RESULTS: 100 µM methyllycaconitine has no inhibitory effects on relaxations, eliminating homomeric α7 subtypes. Subtypes composed of α4ß2 subunits are also eliminated because choline acts as an agonist and dihydro-beta-erythroidine is ineffective. CONCLUSIONS & INFERENCES: Because mecamylamine blocks the relaxations and both choline and cytisine act as agonists in both clasp and sling fibers, the nicotinic receptor subtypes responsible for these relaxations could be composed of α3ß4ß2, α2ß4, or α4ß4 subunits.

Enhanced nicotinic receptor mediated relaxations in gastroesophageal muscle fibers from Barrett's esophagus patients.

BACKGROUND: Increased nicotinic receptor mediated relaxation in the gastroesophageal antireflux barrier may be involved in the pathophysiology of reflux. This study is designed to determine whether the defects we previously identified in gastroesophageal reflux disease patients in- vivo are due to abnormalities of the gastric sling, gastric clasp, or lower esophageal circular (LEC) muscle fibers. METHODS: Muscle strips from whole stomachs and esophagi were obtained from 16 normal donors and 15 donors with histologically proven Barrett's esophagus. Contractile and relaxant responses of gastric sling, gastric clasp, or LEC fibers were determined to increasing concentrations of carbachol and to nicotine after inducing maximal contraction to bethanechol. Muscarinic receptor density was measured using subtype selective immunoprecipitation. KEY RESULTS: Barrett's esophagus gastric sling and LEC fibers have decreased carbachol-induced contractions. Barrett's esophagus sling fibers have decreased M2 -muscarinic receptors and LEC fibers have decreased M3 receptors. Relaxations of all three fiber types are greater in Barrett's esophagus specimens to both high carbachol concentrations and to nicotine following bethanechol precontraction. The maximal response to bethanechol is greater in Barrett esophagus sling and LEC fibers. CONCLUSIONS & INFERENCES: The increased contractile response to bethanechol in Barrett's specimens indicates that the defect is likely not due to the smooth muscle itself. The enhanced nicotinic receptor mediated response may be involved in greater relaxation of the muscles within the high-pressure zone of the gastroesophageal junction during transient lower esophageal sphincter relaxations and during deglutitive inhibition and may be involved in the pathophysiology of gastroesophageal reflux disease.

Characterization of the distal esophagus high-pressure zone with manometry, ultrasound and micro-computed tomography.

BACKGROUND: We sought to determine how the individual components of the distal esophagus and proximal stomach form the gastroesophageal junction high-pressure zone (GEJHPZ) antireflux barrier. METHODS: An endoscopic ultrasound/manometry catheter was pulled through the proximal stomach and distal esophagus in 20 normal subjects. The axial length and width of individual structures on endoscopic ultrasound were measured. The anatomic orientation of gastroesophageal junction (GEJ) components was examined in two organ donor specimens using micro-computed tomography (micro-CT). KEY RESULTS: The three distinct structures identified within the GEJHPZ, from distal to proximal, were as follows: the gastric clasp and sling muscle fiber complex, crural diaphragm, and lower esophageal circular smooth muscle fibers (LEC). The LEC was statistically significantly thicker than adjacent esophageal muscles. These structures were associated with three pressure peaks. The pressure peak produced by the clasp/sling fiber complex often overlapped with the pressure peak from the crural diaphragm. The most proximal peak, associated with the LEC, was significantly greater and bimodal in nine of 20 subjects. This bimodal LEC pressure peak correlated with two areas of thickened muscle observed with ultrasound. Micro-CT of GEJ from organ donors confirmed the two areas of thickened muscle. CONCLUSIONS & INFERENCES: Three distinct anatomic structures, the clasp and sling muscle fibers, crural diaphragm, and LEC combine to form the antireflux barrier of the proximal stomach and distal esophagus. The clasp and sling muscle fibers combine with the crural diaphragm to form a distal pressure profile. The more proximal LEC has a bimodal pressure profile in some patients.

Caregiver cognitive status and potentially harmful caregiver behavior.

The association between caregiver cognitive status and potentially harmful caregiver behavior was assessed in a sample of 180 caregiver-care recipient dyads. Compromised cognitive status was identified in 39% of these informal caregivers. Beyond variance explained by demographic factors, amount of care provided, care recipient cognitive status, and caregiver depressed affect, care recipients reported more frequently being subjected to potentially harmful caregiver behavior when their caregivers evidenced compromised cognitive status. While preliminary, critical areas of caregiver cognition appeared to be deficits in language comprehension and memory. Results indicate that compromised cognitive status is common among informal caregivers of impaired elders and that this may adversely influence the quality of care they provide.

Partial tears of the distal biceps tendon: MR appearance and associated clinical findings.

PURPOSE: To describe the magnetic resonance (MR) appearance and associated clinical findings of partial distal biceps tendon tears. DESIGN: Twenty elbow MR images at 1.5 T, performed over a 7 year period, were reviewed for an appearance of partial tears in the distal biceps. These images were assessed by two musculoskeletal radiologists for the extent of: (a) abnormal signal intensity within the tendon, and the presence of (b) bicipitoradial bursitis, and (c) bony microavulsive injury of the radial tuberosity. Medical records for nine of the 20 cases were reviewed for the clinical findings of ecchymosis, trauma, sensation of a "pop", loss of function, and acuity of onset. RESULTS: Twenty partial distal biceps tendon tears were seen. All displayed an abnormally increased signal in the distal biceps tendon. Three of 20 (15%) showed a 25% to 50% tear, ten of 20 (50%) showed a 50% tear, and seven of 20 (35%) showed a 75% to 90% tear. Bicipitoradial bursitis was seen in 11 of 20 (55%) cases. Bony microavulsive injury of the radial tuberosity was observed in 10 of 20 (50%). Of the nine cases reviewed for associated clinical findings, surprisingly, only three (33%) experienced an acute traumatic episode with an abrupt onset of pain. An insidious onset was reported in four of nine (44%). Sensation of a "pop" was recorded in only two of nine (22%) cases. Ecchymosis and loss of function were not seen in any of the cases. Finally, surgical conformation was obtained for three cases. CONCLUSION: Partial distal biceps tendon tears have a characteristic MR appearance, demonstrate little functional deficit, and may be attritional in their etiology due to the observation of a low number of patients reporting trauma or an acute onset.

Assessing posttraumatic stress disorder with the MMPI-2 in a sample of workplace accident victims.

In this study, the predictive capacity of the Minnesota Multiphasic Personality Inventory-2 Posttraumatic Stress Disorder-Keane (MMPI-2 PK) scale was examined in a sample of trauma victims who experienced a serious workplace-related accident and subsequent injury. In keeping with a number of previous investigations, the PK scale was largely ineffective in identifying posttraumatic stress disorder (PTSD) beyond overall symptom and functional severity. In contrast, sets of clinical and content scales proved to be significant predictors of PTSD. These findings suggest that the PK scale is not particularly useful in detecting PTSD in civilian trauma samples. Clinicians might be best advised to use the MMPI-2 clinical and content scales in their assessment of PTSD in civilian patients presenting with a history of trauma.

Local longitudinal muscle shortening of the human esophagus from high-frequency ultrasonography.

We analyzed local longitudinal shortening by combining concurrent ultrasonography and manometry with basic principles of mechanics. We applied the law of mass conservation to quantify local axial shortening of the esophageal wall from ultrasonically measured cross-sectional area concurrently with measured intraluminal pressure, from which correlations between local contraction of longitudinal and circular muscle are inferred. Two clear phases of local longitudinal shortening were observed during bolus transport. During luminal filling by bolus fluid, the muscle layer distends and the muscle thickness decreases in the absence of circular or longitudinal muscle contraction. This is followed by local contraction, first in longitudinal muscle, then in circular muscle. Maximal longitudinal shortening occurs nearly coincidently with peak intraluminal pressure. Longitudinal muscle contraction begins before and ends after circular muscle contraction. Larger longitudinal shortening is correlated with higher pressure amplitude, suggesting that circumferential contractile forces are enhanced by longitudinal muscle shortening. We conclude that a peristaltic wave of longitudinal muscle contraction envelops the wave of circular muscle contraction as it passes through the middle esophagus, with peak longitudinal contraction aligned with peak circular muscular contraction. Our results suggest that the coordination of the two waves may be a physiological response to the mechanical influence of longitudinal shortening, which increases contractile force while reducing average muscle fiber tension by increasing circular muscle fiber density locally near the bolus tail.

Adult aging and listening patterns for spoken prose: spontaneous segmentation versus self-paced listening.

Young and older adults were allowed to control the delivery rate of spoken prose for later recall using two methods. In one method (spontaneous segmentation), participants were allowed to interrupt speech passages whenever they wished. In the other method (self-paced listening), speech passages were presented in segments, with participants allowed to initiate presentation of subsequent segments via a key-press. Older adults' segment sizes in the spontaneous segmentation condition were unchanged when the passages were presented for a second time. By contrast, pause latencies to initiating subsequent segments in the self-paced listening condition were affected by experience with the passage. Results suggested that the segment sizes selected in the spontaneous segmentation condition were driven by the linguistic structure and prosody of the speech, rather than reflecting ineffective metamemory on the part of the older adults.

Increased expression of CD23 (Fc(epsilon) receptor II) by peripheral blood monocytes of aids patients.

Monocytes expressing the Fcepsilon receptor II (CD23) play important roles in inflammatory and allergic immune responses. We found that peripheral blood monocytes of AIDS patients express increased levels of CD23, compared with monocytes of healthy HIV-1-seronegative individuals (controls) (p < 0.05). We compared expression of monocyte CD23 with expression of monocyte Fcgamma receptors (CD16, CD32, CD64), plasma/serum levels of IgE (also IgM, IgG, IgA), and Th1 (IFN-gamma) and Th2 (IL-4, IL-10) cytokines. We found that monocyte CD23 expression directly correlated with monocyte CD16 expression (p < 0.01, R = 0.58), which was also increased in AIDS patients; there was no correlation with CD32 or CD64 or with soluble factors in plasma/serum (i.e., IgE, IL-4, IL-10, and IFN-gamma). Interestingly, despite the known ability of IL-10 to downregulate monocyte CD23 expression, plasma IL-10 levels were increased in these AIDS patients compared with controls (p < 0.05). We thus evaluated the effect of AIDS and control plasma or rhIL-10 to regulate CD23 expression by monocytes in cultures (24 hr) of healthy human cells +/- treatment with anti-IL-10R blocking antibody. We found that anti-IL-10R blocking antibody treatment had no effect on monocyte CD23 expression in cultures containing AIDS plasma, but increased monocyte CD23 expression in cultures containing control plasma (p < 0.05) or rhIL-10. In conclusion, the identification of increased monocyte CD23 expression in AIDS patients may further characterize the aberrant activated phenotype of monocytes during the immunopathogenesis of HIV-1 disease. Further, monocyte CD23 expression does not appear to be suppressed by the IL-10-enriched environment in AIDS.

Antipsychotic prescription use and costs for persons with schizophrenia in the 1990s: current trends and five year time series forecasts.

Real advances in schizophrenia pharmacotherapy have been made over this decade with the development of more efficacious treatment options with fewer side-effects. These advances have high per-unit direct costs that may have a profound effect on drug budgets of systems caring for persons with schizophrenia. The objective of this study was to describe the changes in utilization and cost for antipsychotic prescriptions by atypical, clozapine, decanoate products, and traditional neuroleptics in a large naturalistic setting, i.e. the Georgia Medicaid population. Secondly, this study forecasted the categorized antipsychotic prescription utilization through the year 2002. Administrative claims data spanning 1990-1997 for Medicaid eligible persons suffering from schizophrenia in the state of Georgia were supplemented with psychiatric institutional data obtained from the Georgia Department of Human Resources. A total of 16227 Medicaid-eligible recipients had a code indicative of schizophrenia (ICD-9-CM=295.(**)) and were at least 16 years of age at the time of their first diagnosis. The mean recipient prescription use and expenditures were tallied for each month of the study and stratified by prescription category (atypical, clozapine, decanoate, and traditional antipsychotic). ARIMA time series models were identified and estimated using these monthly PMPM utilization and expenditures estimates to forecast 5 years beyond the last month of the study. The total use of antipsychotics increased modestly throughout the study period, and the use of atypicals, clozapine, and decanoate products increased substantially, while a decrease was observed for traditional antipsychotics. In 1995 dollars, antipsychotic expenditures increased from a mean of approximately $10 PMPM in 1990 to $95 projected for the year 2002. This transition from traditional oral antipsychotics to atypicals and decanoate products has a profound effect on drug expenditures for systems paying for the care of persons with schizophrenia. Further studies to determine the value of the transitions of therapy described in this study need to be evaluated using a system-wide- or Medicaid perspective.

Repair of rotator cuff tears in golfers.

PURPOSE: Golfers continue to play through the years that rotator cuff disease becomes more common. We sought to establish the results of acromioplasty and rotator cuff repair in golfers, including their ability to return to the sport. STUDY TYPE: Case series. METHODS: Of 30 golfers who underwent 32 rotator cuff repairs, 29 were interviewed, completed a detailed questionnaire, and returned for a physical examination. All of the patients were recreational or regional tournament golfers. Fifteen had open acromioplasty and rotator cuff repair and 16 had arthroscopic acromioplasty and mini-open repair. The average age at surgery was 60 years (range, 39 to 76 years). At surgery, most were moderate size tears (2 to 6 cm(2)). RESULTS: At average follow-up of 37 months (range, 24 to 60 months), all but 3 patients are currently golfing. For patients who are currently golfing, there was no significant difference in handicaps or drive distances at most recent follow-up compared with presymptomatic handicaps and drive distances (P >.05). Twenty-three patients report that they are playing at their presymptomatic competitive level without pain. Three patients report playing at a lower competitive level than before. CONCLUSION: In our experience, acromioplasty and rotator cuff repair predictably allow for eventual return to pain-free golfing at a similar competitive level for most recreational-level athletes.

A statistical interpretive method for neuropsychological test data.

The accurate interpretation of large numbers of neuropsychological tests within a flexible battery approach is a difficult and sometimes controversial process. We present a statistically based method of interpretation (Rohling's Interpretive Method or RIM) and evaluation of neuropsychological data that allows for varying numbers of tests along a varying number of cognitive domains, yet remains psychometrically based. This method requires informed clinical judgment in that the level of confidence for tests, cognitive domains, and global indices are used as the backdrop for interpretive decisions. Specific procedures for use are presented in a systematic, detailed fashion to allow the interested reader to replicate the method. Two case examples are presented: a straightforward case of cerebrovascular insult and a more complicated case of mixed etiology. Examples include a variety of different neuropsychological tests commonly used in a flexible battery approach. A discussion of the practicality, ease of use, and potential limitations of this method are further presented.

Use of simultaneous high-resolution endoluminal sonography (HRES) and manometry to characterize high pressure zone of distal esophagus.

The purpose of this investigation was to separate the high pressure zone (HPZ) of the distal esophagus into its two components, the intrinsic lower esophageal sphincter (LES) and the extrinsic crural diaphragm (CD), using simultaneous esophageal manometry and high-resolution endoluminal sonography. Five normal subjects were studied during end inspiration using a dual manometry/ultrasound catheter. The HPZ in the distal esophagus was characterized ultrasonographically as the CD distally and as an overlap of CD and LES proximally. In four of five volunteers, the initial distal rise in pressure at the HPZ corresponded to imaging of CD rather than imaging of the LES. In all subjects, peak pressure corresponded to an overlap of CD and LES. In conclusion, it is possible to divide the HPZ into its two components, the LES and CD using simultaneous high-resolution endoluminal sonography and esophageal manometry. During end inspiration, the CD contributes to the initial distal rise in pressure at the HPZ. Peak pressure of the HPZ corresponds to an overlap of the LES with the CD.

Validation of volume measurements in esophageal pseudotumors using 3D endoluminal ultrasound.

The purpose of this study was to validate the accuracy and reliability of volume measurements using three-dimensional (3D) endoluminal ultrasound (ELUS) in canine pseudotumor esophageal specimens in vitro. Pseudotumors were created by injecting various volumes of US gel (0.1-1.0 ml) into canine esophageal specimens. A stepping-motor was used to pull either a 9, 12.5 or 20 MHz transducer through the lumen of the specimen at 1.5 mm/s. Images were downloaded to a LIFE computer system for 3D reconstruction. Volume measurements were made by two investigators and compared to spiral CT images. Averaging across all measurements, the average magnitude of error was 8.7% in individual US determinations and 11. 9% in CT measures. Volumes estimated from images spaced 0.5 and 1.0 mm apart, from images in the original and reconstructed planes, and from different scan frequencies, produced percentage errors that were not statistically significantly different from each other on ELUS. 3D ELUS can be used accurately and reproducibly to measure tumor volumes with a low mean percent in vitro.

Three-dimensional esophageal varix model quantification of variceal volume by high-resolution endoluminal US.

BACKGROUND: The purpose of this study was to evaluate the accuracy and reproducibility of three-dimensional volume measurements by high-resolution endoluminal ultrasound in an esophageal varix model. METHODS: An esophageal varix model was made by filling three esophageal dilatation catheters with various volumes of water. A 20 MHz ultrasonography transducer was then pulled along the length of the catheters at a constant rate (1.25 mm/sec) while videotaping the procedure. Cross-sectional surface area measurements of each catheter were taken every second and the cross-sectional surface area was multiplied by the length of each catheter, as determined by high-resolution endoluminal ultrasound, to determine the volume in each catheter. Interobserver variability was calculated, and three-dimensional reconstruction was performed. RESULTS: The measured volumes corresponded closely with the actual volumes with an error ranging from 0% to 15.4%. The correlation between actual and measured volumes was r = 0.988. The interobserver variability ranged from r = 0.951 to r = 0.994. Actual esophageal varices were then imaged in a similar fashion to determine the feasibility of this method in patients with esophageal varices. CONCLUSIONS: High-resolution endoluminal ultrasound is an accurate and reproducible method of measuring volumes in an esophageal varix model and can be used in a clinical setting to determine variceal volume. Volume studies are now underway in human subjects.

Social skills deficits in schizotypal personality disorder.

Evidence of long-standing social difficulties has been well documented in persons with schizophrenia. These deficits are often so rudimentary that a person with schizophrenia may never have developed the skills necessary to present as socially competent. Given the cognitive, biological, and neuroanatomical links between schizophrenia and schizotypal personality disorder (SPD), a study of social skills in persons with SPD may reveal a behavioral link. This study examined persons with SPD and their ability to label emotions in a recognition task, to display socially competent behaviors in a social role-play task, and to select appropriate behaviors from a multiple choice measure of social behavior. Results indicated that the performance of persons with SPD was similar to previously published findings in persons with schizophrenia. In terms of emotion recognition, the SPD group's ability to label positive emotions was significantly worse than their ability to label other emotions. Persons with SPD performed significantly worse than matched control participants on a social role-play task. However, the groups were equivalent in their ability to select socially appropriate behavior from a multiple choice measure. These results suggest that persons with SPD display social skills which mirror those previously reported in persons with schizophrenia.