Michael H. Sacks

Muscle-derived stem cells seeded into acellular scaffolds develop calcium-dependent contractile activity that is modulated by nicotinic receptors

OBJECTIVES To explore the contractile activity and physiologic properties of muscle-derived stem cells (MDSCs) incorporated into small intestinal submucosa (SIS) scaffolds. METHODS MDSCs were harvested from mice hind leg muscles using the preplate technique and stably transfected with a plasmid to express the LacZ reporter gene. Fifty different preparations of SIS cultured with MDSCs (MDSC/SIS) or SIS alone were incubated at 37 degrees C for 1, 4, and 8 weeks and also were mounted in a bath to measure the isometric contractions. RESULTS LacZ and Masson-trichrome staining revealed MDSCs could migrate into and distribute throughout the SIS and form myotubes. In MDSC/SIS, spontaneous contractile activities were noted in the 4-week (five of six specimens) and 8-week (eight of eight specimens) cultures, but not in 1-week cultures (n = 11). All SIS control groups after 1 (n = 11), 4 (n = 6), and 8 (n = 8) weeks of incubation did not show any activity. In most of the 4-week, and all of the 8-week, MDSC/SIS cultures, the frequency and amplitude of spontaneous contractile activities were decreased by succinylcholine 10 microM and 20 microM. Electrical field stimulation, carbachol, and KCl did not alter the frequency, amplitude, or pattern of spontaneous contractile activities in MDSC/SIS. Spontaneous contractile activities were blocked by Ca(32+)-free Krebs solution with ethyleneglycoltetraacetic acid 200 microM and distilled water. CONCLUSIONS MDSCs could be incorporated into SIS-forming myotubes capable of contracting. The contractile activity of this three-dimensional construct is Ca(2+) dependent and is modulated by nicotinic receptors. MDSC seeding of an acellular matrix may become a functional sling to reengineer the deficient sphincter or as contractile bladder augmentation.

Triglycidylamine Crosslinking of Porcine Aortic Valve Cusps or Bovine Pericardium Results in Improved Biocompatibility, Biomechanics, and Calcification Resistance: Chemical and Biological Mechanisms

We investigated a novel polyepoxide crosslinker that was hypothesized to confer both material stabilization and calcification resistance when used to prepare bioprosthetic heart valves. Triglycidylamine (TGA) was synthesized via reacting epichlorhydrin and NH(3). TGA was used to crosslink porcine aortic cusps, bovine pericardium, and type I collagen. Control materials were crosslinked with glutaraldehyde (Glut). TGA-pretreated materials had shrink temperatures comparable to Glut fixation. However, TGA crosslinking conferred significantly greater collagenase resistance than Glut pretreatment, and significantly improved biomechanical compliance. Sheep aortic valve interstitial cells grown on TGA-pretreated collagen did not calcify, whereas sheep aortic valve interstitial cells grown on control substrates calcified extensively. Rat subdermal implants (porcine aortic cusps/bovine pericardium) pretreated with TGA demonstrated significantly less calcification than Glut pretreated implants. Investigations of extracellular matrix proteins associated with calcification, matrix metalloproteinases (MMPs) 2 and 9, tenascin-C, and osteopontin, revealed that MMP-9 and tenascin-C demonstrated reduced expression both in vitro and in vivo with TGA crosslinking compared to controls, whereas osteopontin and MMP-2 expression were not affected. TGA pretreatment of heterograft biomaterials results in improved stability compared to Glut, confers biomechanical properties superior to Glut crosslinking, and demonstrates significant calcification resistance.

A tissue‐engineered suburethral sling in an animal model of stress urinary incontinence

To create and evaluate the functional effects of a tissue‐engineered sling in an animal model of stress urinary incontinence (SUI).

Resident Response to Patient Suicide

This paper describes the responses of psychiatry trainees to the suicide of a patient, either their own or a colleague’s, and how these responses may be influenced by the institutional and peer group dynamics. In many ways, residents’ reactions resemble those of seasoned clinicians. However, significant differences were noted which related to the formative nature of their professional identities and their sense of being evaluated by peers and supervisors. Substantive responses to the suicide were noted in the other trainees. Program recommendations are made which may decrease the traumatogenic potential of a suicide and foster personal and professional growth.

EFFECTIVENESS IN PSYCHIATRIC CARE. I, A CROSS-NATIONAL STUDY OF THE PROCESS OF TREATMENT AND OUTCOMES OF MAJOR DEPRESSIVE DISORDER

Recent research suggests that, despite the development of effective psychiatric treatment, there is marked underuse of care. This pilot study had the objective of dissecting the process of care in an attempt to understand outcomes for patients with major affective disorder and for their families. Twenty-four patients with a DSM-III diagnosis of major affective disorder were identified 12 to 18 months after hospital admission in three countries (Italy, Japan, and the United States). The patients, their families, and their doctors were interviewed separately and then together, using instruments measuring delivery of treatment (using an ideal treatment criteria set) and percentage of achievement of treatment goals. These measures were then (using parametric and nonparametric statistics) correlated with resolution of the index episode and the patients global outcome (using the Global Assessment Scale). The data demonstrated that physicians delivered about half (52%) and, subsequently, achieved about half (54%) of what would be considered ideal care to patients and other family members. The mean resolution of the index episode at follow-up was only 3.0 (on a 0- to 5-point scale). There was a significant positive association between the most important outcome measure, i.e., the resolution of the episode, and the achievement of treatment goals for both the patient (p <07) and the family (p <05). Patients and families with the best resolutions received significantly more good treatment than those with the worst resolutions (p <02), most notably with regard to medication (p <002).

Unrecognized drug dependence and withdrawal in the elderly

The clinical diagnosis of drug abuse is frequently omitted from the differential diagnosis of transient fevers, arrhythmias and changes in mental status in the elderly despite the high risk of iatrogenic dependence in this age group. In pursuit of symptomatic relief from unrecognized depressions and from the chronic ailments of advancing age, the elderly receive many medications from numerous physicians. Therapeutic interventions are often duplicated or contradictory and result in the co-administration of tranquilizers, sedatives and analgesics. The result may be dependence which the patient and physician fail to recognize or to diagnose in the presence of withdrawal symptoms. In this report we present two such cases.

Applicants’ Perceptions of Psychiatric Residency Training Programs

The authors report the results of a survey of senior medical students who matched to a PGY-1 position in psychiatry. With a 64% response rate, the authors found the following: 1) senior medical students were generally satisfied with the program that they plan to attend; 2) the students utilized nonprogrammatic features heavily in their decision making; and 3) there appeared to be subgroups of students defined by demographic (i.e., gender and age) and decision-making properties (i.e., time of decision) that choose programs with fundamentally different aims in mind.

Seclusion and Restraint as Measures of the Quality of Hospital Care: Any Exceptions?

The Joint Commission has recently included seclusion and restraint as quality-of-care indicators for hospital-based inpatient psychiatric services. Their inclusion is the result of abuse of these practices, wide variation across hospitals, and cultural influences, including the consumer and recovery movements. Over the next few years, these indicators will increasingly influence treatment modalities available to hospitalized patients. This Open Forum provides a brief history of changing attitudes toward use of seclusion and restraint. It describes three clinical scenarios that highlight appropriate and humane use of seclusion and restraint and that illustrate the clinical complexities associated with their use. Potential unforeseen consequences of the reduction or elimination of seclusion and restraint are described.

AUTOMATED SEGMENTATION OF THE RIGHT HEART USING AN OPTIMIZED SHELLS AND SPHERES ALGORITHM

We have developed a novel framework for medical image analysis, known as shells and spheres. This framework utilizes spherical operators of variable radius centered at each image pixel and sized to reach, but not cross, the nearest object boundary. Statistical population tests are performed on adjacent spheres to compare image regions across boundaries. Previously, our framework was applied to segmentation of cardiac CT data with promising results. In this paper, we present a more accurate and versatile system by optimizing algorithm parameters for a particular data set to maximize agreement to manual segmentations. We perform parameter optimization on a selected 2D slice from a 3D image data set, generating effective parameters for 3D segmentation in practical computational time. Details of this approach are given, along with a validated application to cardiac MR data.

Digitalis delirium: psychiatric considerations.

Digitalis is a ubiquitous drug in modern clinical medicine and digitoxicity is one of the more common iatrogenic disorders. Psychiatric problems are often overlooked as manifestations of digitalis excess and may range from mild disorientation, lethargy, or restlessness to full blown delirium. In this paper we discuss two patients who presented to a psychiatric inpatient unit and were later found to be digitoxic. Psychiatrists are advised to consider digitalis as a possible cause of mental abnormalities and are reminded that psychiatric signs may be the first indication of a potentially lethal drug toxicity. Psychiatric patients may also be at special risk for the development of digitoxicity because of erratic drug taking, electrolyte imbalance or increased autonomic tone.