Mechanisms of functional improvement in a 2-year trial of cognitive enhancement therapy for early schizophrenia.

BACKGROUND: Cognitive rehabilitation has emerged as an effective treatment for addressing cognitive impairments and functional disability in schizophrenia; however, the degree to which changes in various social and non-social cognitive processes translate into improved functioning during treatment remains unclear. This research sought to identify the neurocognitive and social-cognitive mechanisms of functional improvement during a 2-year trial of cognitive enhancement therapy (CET) for early-course schizophrenia. METHOD: Patients in the early course of schizophrenia were randomly assigned to CET (n=31) or an enriched supportive therapy control (n=27) and treated for up to 2 years. A comprehensive neurocognitive assessment battery and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) were completed annually, along with measures of functioning. Mediator analyses using mixed-effects growth models were conducted to examine the effects of neurocognitive and social-cognitive improvement on functional change. RESULTS: Improvements over 2 years in neurocognition and the emotion management branch of the MSCEIT were found to be significantly related to improved functional outcome in early-course schizophrenia patients. Neurocognitive improvement, primarily in executive functioning, and social-cognitive change in emotion management also mediated the robust effects of CET on functioning. CONCLUSIONS: Improvements in neurocognition and social cognition that result from cognitive rehabilitation are both significant mediators of functional improvement in early-course schizophrenia. Cognitive rehabilitation programs for schizophrenia may need to target deficits in both social and non-social cognition to achieve an optimal functional response.

Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. II. Two-year effects of a controlled study on relapse and adjustment. Environmental-Personal Indicators in the Course of Schizophrenia (EPICS) Research Group.

We demonstrated earlier that a novel family psychoeducational approach and an individual social skills training approach designed for patients living in high-expressed emotion households each reduced schizophrenic relapse by one-half when compared with medication controls in the 1st year after hospital discharge. The combination of treatments resulted in no relapse. Results have now been obtained after 2 years of continuous treatment. By 24 months, a persistent and significant effect of family intervention on forestalling relapse was observed, but the effect of social skills training was lost late in the 2nd year. There was no additive effect on relapse that accrued to the combination of treatments. Beyond 2 years, however, the effect of family intervention was likely compromised as well. Treatment effects on the adjustment of survivors were circumscribed, due, in part, to study design characteristics. Effects generally favored the social skills-alone condition at 1 year and the family condition or combined family/social skills condition at 2 years.

Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. I. One-year effects of a controlled study on relapse and expressed emotion.

Relapse rates averaging 41% in the first year after discharge among schizophrenic patients receiving maintenance neuroleptic treatment led to the development of two disorder-relevant treatments: a patient-centered behavioral treatment and a psychoeducational family treatment. Following hospital admission, 103 patients residing in high expressed emotion (EE) households who met Research Diagnostic Criteria for schizophrenia or schizoaffective disorder were randomly assigned to a two-year aftercare study of family treatment and medication, social skills training and medication, their combination, or a drug-treated condition. First-year relapse rates among those exposed to treatment demonstrate a main effect for family treatment (19%), a main effect for social skills training (20%), and an additive effect for the combined conditions (0%) relative to controls (41%). Effects are explained, in part, by the absence of relapse in any household that changed from high to low EE. Only the combination of treatment sustains a remission in households that remain high in EE. Continuing study, however, suggests a delay of relapse rather than prevention.

Metacarpal fracture angulation decreases flexor mechanical efficiency in human hands.

The most common fracture of the hand occurs at the neck of the metacarpal. Despite clinical studies, controversy remains as to how much fracture angulation should be tolerated before more aggressive reduction is required. A controlled biomechanical model was used to simulate fifth metacarpal head fractures in fresh human cadaveric hands. Fracture angulation was varied from 0 to 90 degrees at 10-degree intervals. We measured tendon excursion, tendon load, and work required to flex the small finger from full extension to full flexion with 10-degree incremental increases in vertex-dorsal angulation. Repeated measures analysis of variance revealed a significant decay in the efficiency of the flexor system when fracture angulation exceeded 30 degrees. Tendon excursion, load, and work requirements were all increased, confirming the detrimental effect of excessive fracture angulation on hand mechanics and function.

Mechanical analysis of explanted silicone breast implants.

Smooth-walled silicone gel breast implants (n = 25) were removed from 15 women after implantation times that varied from 23 to 216 months (mean = 117 months; SEM = 12.9). Strips of implant shells were tested to failure by computer-controlled tensiometer. Regression analysis revealed significant negative correlation between age of implantation and shell strength (p < 0.05), shell toughness (p < 0.05), and shell elasticity (p < 0.05). These data suggest that exposure to the in vivo environment weakens silicone gel breast implant shells over time.

Incidence and natural history of saline-filled breast implant deflations: comparison of blunt-tipped versus cutting and tapered needles.

The silicone shells of breast implants are known to fail. When failure occurs in saline-filled implants, the consequences are always ultimately symptomatic. Failure may be due to shell elastomer fatigue, fold-flaw cracking, faulty valve mechanisms, trauma, and microperforations (defined as perforations that are too small to be seen with the unassisted eye). To determine the incidence and natural history of microperforations, a major manufacturer of saline-filled breast implants was contacted. Over a 30-month period, 289,033 saline implants were sold, and 2844 were subsequently returned due to perioperative deflation. By using a rigorous and reproducible method of evaluating returned deflated saline-filled breast implants, it was found that 197 (0.068 percent of all implants sold) sustained needle damage at the time of insertion and went on to deflate within 6 months. Of the implants returned, overall 6.93 percent were found to have sustained needle trauma as the cause of the deflation, and the incidence appears to be increasing with time. The actual incidence of needle-related deflations may be significantly greater, since these data reflect only those implants which are voluntarily returned to the manufacturer. As a second part of this study, a segment of the silicone shell from a saline-filled breast implant was tested to determine the resistance to puncture using blunt-tipped, tapered, and cutting needles. The blunt-tipped needle required 6.6 times more force to puncture the shell than a cutting needle (p = 0.0011) and 3.2 times more force than a tapered needle (p = 0.0052). The difference in force needed to puncture the shell for a tapered and a cutting needle was not statistically significantly different (p = 0.5045). Microperforations do occur in the operating room and are responsible for a significant percentage of early (less than 6 months) deflations. Blunt needles require significantly more force to puncture the shell of an implant than do cutting and tapered needles, and their use may reduce the incidence of microperforations and subsequent implant deflations.

Full-thickness skin wound explants in tissue culture: a mechanical evaluation of healing.

This study was designed to evaluate biomechanically defined wound healing in full-thickness skin explants in tissue culture. The requirement for preculture incubation of wounds in situ was characterized. Full-thickness skin incisions were made in 44 rats and closed immediately. Wounds were incubated in situ for 0, 12, 24, 36, 48, 72, or 96 hours before harvesting and placement into tissue culture media for 6 weeks. Healing was evaluated by biomechanical criteria: tensiometric distraction to wound rupture generated true stress and energy absorption data. Burst-strength (maximum true stress) and toughness (energy absorption) were five times higher in the 48-hour group than in any other group; other groups were not different from each other. This study demonstrates long-term survival of full-thickness skin in culture and shows that full-thickness skin explants heal in tissue culture. Possible explanations for the narrow window of opportunity for harvest (48 hours, no more and no less) are discussed.

Optimization of the MGH repair using an algorithm for tenorrhaphy evaluation.

Previous investigations have demonstrated the superior strength and toughness of the MGH four-strand tendon repair technique and shown that it neither weakens during maximum tendon softening nor interferes with healing in an in vivo rabbit model. In the current study, the biomechanical performance of the modified Becker (MGH) and the modified Kessler repairs were compared in situ using a dynamic human cadaveric model to evaluate strength, toughness, glide efficiency, and operator variability. Three different surgeons performed a total of 42 zone II flexor digitorum profundus repairs in 14 fresh human cadaver hands. The modified Becker (MGH) repairs were stronger (79 +/- 3 versus 64 +/- 4 N; p < 0.01) and tougher (0.092 +/- 0.002 versus 0.078 +/- 0.003 J; p < 0.01) than the Kessler repairs while allowing equally efficient glide (32 +/- 6 versus 33 +/- 4 percent; p > 0.9). Strength was operator-dependent only for the modified Kessler repair (p < 0.005). We then established the optimal configuration of the MGH tenorrhaphy (number of preloaded crosses on either side of the tendon transection) by examining gap resistance ex vivo. Fifty-one MGH flexor tendon repairs were performed on explanted fresh human cadaver tendons. The experimental groups were randomly assigned to receive 0, 1, 2, 3, or 4 crosses on each side of the tenorrhaphy. Strength and toughness to gap formation and to ultimate failure were assessed tensiometrically. The MGH two-cross configuration was most resistant to gap formation (peak load 39 +/- 3 N; p < 0.05), establishing this configuration as the optimal design of this four-strand crisscrossing repair technique. The augmented Becker (MGH) repair is significantly stronger and tougher than the modified Kessler repair and demonstrates no operator dependence. It is a superior technique for zone II tenorrhaphy in the human hand. An algorithm is presented as a systematic approach that includes the important elements necessary for the rigorous biomechanical evaluation of any tendon repair technique.

Effects of laser versus scalpel tenolysis in the rabbit flexor tendon.

The use of surgical lasers has been shown to decrease adhesion formation as compared with scalpel control groups in various surgical procedures. The potential benefits of laser technology have not been assessed in the treatment of adherent tendons. The current study was designed to first develop a reliable and reproducible model for consistent adhesion formation following flexor tendon trauma. The second goal was to compare the effects of laser tenolysis procedures on tendon gliding with those of traditional scalpel tenolysis. In phase I, the adhesion-induction model utilized bilateral standardized crush- abrasion injuries to the hind limb digital flexor tendons of New Zealand White rabbits. Following 4 weeks of immobilization, the animals were sacrificed, and peritendoneal adhesions were assessed biomechanically. A significantly higher maximal force was required to extract the adherent tendons from the foot as compared with nontraumatized control tendons. In phase II, six groups of animals underwent the same standardized tendon trauma. Four weeks later the rabbits were randomly assigned to undergo either CO2 laser or holmium:YAG laser tenolysis on one foot. Scalpel lysis was used on the contralateral foot and served as an intraindividual control. Biomechanical assessment was performed at 1, 2, and 4 weeks following tenolysis. Significantly less force was required to extract the treated tendons at 1 and 2 weeks following holmium:YAG laser tenolysis when compared with scalpel or CO2 laser tenolysis. After 4 weeks, differences between holmium:YAG and CO2 laser and scalpel treatment were no longer significant. Extracted tendons were pulled apart to failure, and no difference in breaking strength was noted between groups. We conclude that holmium:YAG laser tenolysis results in easier tendon gliding as compared with scalpel or CO2 laser tenolysis at early time points. Laser tenolysis does not affect intrinsic tendon strength.

Skin closure with dye-enhanced laser welding and fibrinogen.

The topical application of wavelength-specific dye and fibrinogen has been used to enhance laser closure of vascular anastomoses. We compared the closure of skin incisions by two different dye-enhanced, fibrinogen-based laser welding systems [argon laser (power density 4.78 W/cm2) with fluorescein isothiocyanate dye (n = 32) and diode laser (power density 9.55 W/cm2) with indocyanine green dye (n = 32)] with closure by interrupted 5-0 nylon suture (n = 64) and examined tensile strength, hydroxyproline production, histology, and cosmesis. Two 3-cm full-thickness incisions were made on the shaved backs of 64 rats. One incision was closed with suture, whereas the other, after treatment with the appropriate dye, was welded with either argon- or diode-lasered fibrinogen. At postoperative days 5, 10, 15, and 28, the closure sites were harvested and sectioned for analysis. Initially, wounds closed with argon-lasered fibrinogen showed less inflammatory response, greater collagen production (34.61 +/- 0.74 mg/gm), and greater mean peak stress at rupture (64.85 lbs/in2) than those closed with suture (16.42 +/- 3.20 mg/gm, 26.68 lbs/in2) (p less than 0.05). By 15 days, both argon and diode laser closures are superior in strength and collagen production to suture closure (p less than 0.05). At 28 days, diode laser closures (1315.60 lbs/in2) are stronger than suture closures (998.09 lbs/in2), whereas both are stronger than argon laser closures (813.16 lbs/in2) (p less than 0.05). Cosmetically, argon-welded wounds consistently appeared finer and lacked cross-hatched suture scars.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous versus toxin-induced diabetes in rats: a mechanical comparison of two skin wound-healing models.

This study was designed to compare skin wound healing in three groups of Wistar rats: normal, genetically diabetic, and streptozotocin-induced diabetic. All diabetic animals received daily insulin. Full-thickness midline dorsal skin wounds were analyzed biomechanically for strength, toughness, and elasticity (Young's modulus) at 1 and 3 weeks after wounding. Wounds from normal controls were the strongest, toughest, and least compliant. Genetically diabetic rat wounds were the weakest and had the lowest elastic modulus. Wounds from the streptozotocin-induced rats were intermediate for all parameters measured (ANOVA, p = 0.001). Toxin-induced diabetes is less detrimental to skin wound healing than diabetes of endogenous origin. Whether this is due to basic differences in the models or to differences in duration of diabetes is unknown.

Social skills training and endogenous depression.

The clinical response to social skills training was studied in four women with definite endogenous depression (melancholia) to ascertain if a behavioral intervention could be effective with more severe and pervasive affective syndromes. Three of four patients responded to social skills training, although both patients available for longitudinal follow-up relapsed within 24 months post-treatment. Implications for research and practice are discussed.

Mycobacterium avium/Mycobacterium intracellulare Complex-Associated Arthritis Masquerading as a Seronegative Rheumatoid Arthritis.

Mycobacterium avium/Mycobacterium intracellulare[cf1] complex (MAC) is a rare cause of tenosynovitis. We describe a case in which a previously healthy patient developed bilaterally symmetric synovitis and was treated with disease modifying anti rheumatic drugs (DMARDs); the synovitis progressed into a bilaterally symmetric chronic granulomatous tenosynovitis that was uncontrollable despite a synovectomy and DMARD therapy. Three years after developing symptoms, and 2 1/2 years after her diagnosis of rheumatoid arthritis, MAC was cultured from synovial fluid. All DMARDS were stopped, and the patient received a total of 24 months of triple antibiotic therapy. All swelling and stiffness resolved after 7 months of therapy. The patient remains asymptomatic two months after completion of antibiotic therapy. Rheumatologists and other arthritis specialists need to include MAC in their differential diagnosis of seronegative symmetrical inflammatory arthritis.

Debilitating silicone granuloma of the penis and scrotum.

The restoration and improvement of body contour have intrigued surgeons for over 100 years, generating much interest in the subcutaneous/intradermal injection of highly viscous fluids. The local complications of liquid silicone injection have been well documented over the past 30 years. Although Dow-Corning has not made medical-grade liquid silicone available for use in humans without an approved research application since 1966, practitioners, both licensed and unlicensed, have administered these injections worldwide for a variety of indications throughout the body. There is little or no information concerning the adulteration of these injectates. To date, there have been four case reports of penile injections--the indications being evenly split between the treatment of impotence/sexual inadequacy and augmentation. The most recent description was published in 1982. We present a case of debilitating silicone granuloma of the penis and scrotum secondary to large-volume injections into the corpora cavernosae and penile soft tissues administered in Belgium 14 years prior to presentation. The development of a silicone foreign body reaction, massive edema, and subsequent impotence lends itself to a clinical diagnosis and aggressive treatment with wide local excision and appropriate soft-tissue coverage. The metabolic fate of silicone in vivo remains inadequately characterized and a fertile area for research as new methods involving nuclear magnetic resonance spectroscopy have been devised to identify silicone and highly coordinated silicone complexes.

Central plus peripheral stimulation by androgen is necessary for complete restoration of copulatory behavior in the male hamster.

Male golden hamsters were castrated and received a unilateral intrahypothalamic implant of either testosterone propionate (TP) or estradiol benzoate (EB). Half the animals from each group also received 5 alpha-dihydrotestosterone (DHT) via subcutaneous silastic capsule implants. The males were tested in a three-part design (intact, castrate, implant) to determine the effectiveness of intracerebral alone versus intracerebral plus systemic hormone regimens in restoring copulatory behavior following castration. All treatment regimens reinstated ectopic and normal mounting behavior to levels comparable to those seen in the intact animals. However, only those animals which received DHT systemically in addition to intracerebral implantation of TP or EB showed intromissions after castration. Both EB and TP groups with systemic DHT had intromission levels comparable to the controls by day 14 after implantation. The results point to a dual mechanism for the regulation of sexual behavior in the male hamster. A central hormone-sensitive mechanism is found in the anterior hypothalamic-preoptic region which is necessary for mounting behavior to be expressed. Androgen can affect stimulation at this level via conversion (aromatization) to estrogen. In addition, a peripheral hormone-sensitive mechanism which is necessary for intromission responses depends on the presence of nonaromatizable androgen for maintenance of its sensory feedback channels. The complete copulatory behavior pattern occurs only when both systems are hormone stimulated.

Mechanical analysis of tendon suture techniques.

The relative strengths of seven methods of tendon repair were measured by mechanical disruption in an effort to determine the quality of a technique using loaded criss-crossing sutures and a running epitenon stitch. Fifty-seven calcaneus tendons were harvested from adult New Zealand white rabbits and randomized for transection. Standardized oblique transections were repaired with nylon using modified Halsted peripheral suture; modified Kessler technique; Kessler core stitch alone; running peripheral epitenon stitch; modified Becker technique #1; modified Becker technique #2; and a new augmented Becker repair. Sixteen additional rabbits each had bilateral tendon repairs in situ, one leg by Kessler and the other by the new augmented Becker repair technique. Half were lethally injected after 2 weeks and half after 4 weeks. Tenorrhaphies were pulled apart at constant speed until a gap of 1 mm was observed. Strength (maximum stress) and toughness (energy absorption to gap formation) were calculated. At time 0 the new augmented Becker repairs were the strongest, followed by the Kessler and Becker #2 tenorrhaphies. Kessler repairs were weaker at 2 weeks and then gained in strength; new augmented Becker repairs did not weaken at the 2-week point and demonstrated significant gains in strength after 4 weeks in vivo. The new augmented Becker repair was the strongest by a significant margin at all time points.