Biomedical subjects
D McKay
Publications and source records attributed to D McKay.
Stigmatising pharmaceutical advertisements.
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The Overvalued Ideas Scale: development, reliability and validity in obsessive-compulsive disorder.
The presence of overvalued ideas in obsessive-compulsive disorder (OCD) has been theoretically linked to poorer treatment outcome [Kozak, M. J. & Foa, E. B. (1994). Obsessions, overvalued ideas and delusions in obsessive-compulsive disorder. Behaviour Research and Therapy, 32, 343-353]. To date, no measures have been developed which quantitatively assess levels of overvalued ideas in obsessive-compulsives. The present studies examined the psychometric properties of a scale developed to measure this form of psychopathology, the Overvalued Ideas Scale (OVIS). In study 1, 102 patients diagnosed with OCD were administered a battery of instruments including the OVIS at baseline and two weeks later, prior to initiating treatment. Results indicate that the OVIS has adequate internal consistency reliability (coefficient alpha = 0.88 at baseline), test-retest reliability (r = 0.86) and interrater reliability (r = 0.88). Moderate to high levels of convergent validity was found with measures of obsessive-compulsive symptoms, a single item assessment of overvalued ideas and psychotic symptoms. Medium levels of discriminant validity with measures of anxiety and depression was obtained in this study. Individuals determined to have high OVI showed greater stability of this pathology than those with lower OVI, suggesting that overvalued ideas are stable for extreme scorers. In study 2 a total of 40 patients participated who were diagnosed with OCD. The same battery of instruments was administered as in study 1, as well as the Beck Depression Inventory and Beck Anxiety Inventories. Results were similar to that obtained in study 1, including a relative lack of discriminant validity with self-report measures of depression and anxiety. It is suggested that further research with the OVIS may show predictive value in treatment outcome studies of OCD.
Survival of life on asteroids, comets and other small bodies.
The ability of living organisms to survive on the smaller bodies in our solar system is examined. The three most significant sterilizing effects include ionizing radiation, prolonged extreme vacuum, and relentless thermal inactivation. Each could be effectively lethal, and even more so in combination, if organisms at some time resided in the surfaces of airless small bodies located near or in the inner solar system. Deep within volatile-rich bodies, certain environments theoretically might provide protection of dormant organisms against these sterilizing factors. Sterility of surface materials to tens or hundreds of centimeters of depth appears inevitable, and to greater depths for bodies which have resided for long periods sunward of about 2 A.U.
Two-year follow-up of behavioral treatment and maintenance for body dysmorphic disorder.
Recent research has suggested that body dysmorphic disorder (BDD) is part of the obsessive-compulsive compulsive spectrum of disorders. As such, it has been hypothesized that these disorders respond in a similar manner to obsessive-compulsive disorder when behavioral interventions are used. A continuation of follow-up was conducted with a group of patients with BDD following treatment. Ten patients completed an intensive behavioral therapy program and either participated in a 6-month maintenance program or served as controls. At 12-, 18-, and 24-month follow-up assessments, patients participating in the maintenance program were more effective at managing limited symptom return and had significantly lower anxiety and depression. Both groups remained improved for acute symptomatology and behavioral avoidance. The results suggest that maintenance programs following behavioral treatment are effective in preventing symptom relapse and assist in patient self-management of lapses typically associated with BDD.
Body dysmorphic disorder: a preliminary evaluation of treatment and maintenance using exposure with response prevention.
In recent investigations, body dysmorphic disorder (BDD) has been shown to share common etiological and symptom presentation to obsessive-compulsive disorder (OCD). When treating BDD, there have been some investigations suggesting that exposure with response prevention is effective in alleviating symptoms. Ten patients diagnosed with BDD participated in a study examining the effects of treatment and maintenance using exposure with response prevention. They received a standard behavior therapy protocol which consisted of exposure in vivo and in imagery, with response prevention. Symptom severity, depression, anxiety, and avoidance were assessed weekly during treatment. Following treatment, a 6-month maintenance program was instituted for five patients, with the other five serving as controls. Patients in the maintenance program were assessed bi-weekly with all measures and a 6-month follow-up was conducted. Patients improved for measures of avoidance, BDD symptoms, depression and anxiety when using exposure with response prevention. Although all patients remained symptom free at follow-up, those in the maintenance program continued to improve. Based on these results, BDD appears to be amenable to exposure with response prevention treatment. Additional treatment gains can be obtained when structured maintenance programs are implemented.
A maintenance program for obsessive-compulsive disorder using exposure with response prevention: 2-year follow-up.
Recent literature has emphasized the importance of instituting procedures for preventing relapse in obsessive-compulsive disorder (OCD). This study presents data documenting the effect of a maintenance program on the long term (2-year) adjustment of a group of patients with OCD treated with exposure and response prevention. Results indicate that patients maintained their gains for the 2-year follow-up period on measures of anxiety associated with avoidance (Behavioral Avoidance Tests), obsessions, compulsions, and anxiety. Further, patients were able to effectively manage situations defined as lapses (limited symptom return) effectively without additional therapist intervention. However, as in a previous report, treatment gains for depression were not well established. It is concluded that sessions prior to treatment termination which focus on relapse prevention methods focus on additional psychological symptoms aside from the acute disturbance of OCD.
An analysis of the use of the telephone in the management of patients in skilled nursing facilities.
OBJECTIVE: To characterize the nature of telephone communication in the care of patients in skilled nursing facilities, noting numbers of calls, reasons for communication, and the outcomes of the interactions, and to implement a voice mail system to manage the burden of communication more effectively and describe the impact of this system. DESIGN: An archival descriptive study of phone message data covering a period of 1 year in a defined population of nursing home patients, with an intervention and an evaluation of a voice mail system at the conclusion of the year's study. SETTING: A long-term care practice associated with an urban family practice residency program. PARTICIPANTS: Medical care providers, the staffs of 13 skilled nursing facilities, and an average of 207 covered patients followed for 1 year. INTERVENTION: At the termination of the descriptive study, a voice mail system was instituted, and the impact on phone communication was documented. MAIN OUTCOME MEASURES: Total numbers of calls were tabulated by patient and by facility. Reasons for calls, outcomes, and timing were tabulated. The impact of a voice mail system on the communication between nursing home staff and medical providers was characterized. RESULTS: A total of 10,264 calls were received from 13 skilled nursing facilities in regard to an average of 207 continuously covered long-term care patients, which is an average of nearly 50 calls per patient per year. Acute illness accounted for only 5% of calls, and most communications were routine. Though a new treatment was instituted about one-third of the time, no new order was issued in response to 23% of received calls. Hospitalization occurred as the result of about one in two hundred calls. A recent tabulation of 692 calls received during 1 month revealed that 93% of calls are now received through voice mail and about one in five of these calls do not need to be returned. CONCLUSIONS: There is a significant telephone call burden associated with care of patients in skilled nursing facilities. Most of these calls are routine, regulation driven, and often no return call is necessary. For many reasons, including poor reimbursement, much of the medical care delivered occurs as a result of these calls, and methods of managing the communication burden to allow prioritization both by the staff nurse and the physician need to be found. In the practice described, the voice mail system is a positive step in this direction.
CD59 and CD48 expressed by rat retinal pigment epithelial cells are major ligands for the CD2-mediated alternative pathway of T cell activation.
The alternative CD2-mediated pathway of T cell activation, which is independent of MHC/peptide recognition by the TCR/CD3 complex, is dependent upon two signals being received by the CD2 molecule. The natural ligand for CD2 is CD58, but controversy exists over alternative or additional ligands that could deliver the second signal in vivo. We have used rat retinal pigment epithelial cells (RPE), which lack temperature-insensitive ligands for CD2 adhesion, to study Ag-independent T cell activation. Rat RPE cells expressed high levels of CD59 and low levels of another potential CD2 ligand, CD48, both in vitro and in the in vivo model of experimental autoimmune uveoretinitis. When increasing numbers of syngeneic T cells were added to microwell cultures of rat RPE cells, the T cells, even in the absence of any exogenous stimulant in the cultures, underwent spontaneous proliferation. This effect required metabolically active RPE cells, and was IL-2 driven and enhanced in the presence of indomethacin. Proliferation was modulated by phosphatidylinositol-phospholipase C treatment of the RPE, and blocked by mAbs to CD59. Ab cross-linking of CD48 but not CD59 on the RPE was found to induce messenger RNA expression for IL-1 beta, which together with constitutively expressed IL-6 are required costimulatory factors for T cell activation through CD2. This is the first demonstration in a fully syngeneic system that bi-directional signaling involving CD59 and CD48 molecules expressed by physiologically normal, nonhematopoietic, cells can trigger T lymphocyte activation and proliferation through autocrine IL-2 production in the absence of Ag.
Plasma separation for artificial liver support.
A bioartificial liver (BAL) support system, using plasma separation, has been developed to support acute liver failure patients. This study examined 14 consecutive BAL treatments in nine patients with severe acute liver failure. We report methods to achieve and manage plasma separation for an extended period of time. The mean duration of a BAL treatment was 435 minutes, with 26-59 liters of blood processed. Ionized hypocalcemia resulting in muscle twitching was a side effect of the therapy. Ionized calcium levels decreased significantly (P < .02) after BAL treatment; however, total calcium levels increased (P < .05). No significant changes were noted in heart rate, electrocardiogram [Q-T (Q-Tc) interval], blood pressure, prothrombin time, partial thromboplastin time, hematocrit, platelet count and serum phosphorous, magnesium, glucose, and pH. Plasma fibrinogen levels decreased significantly (P < .002). Ionized hypocalcemia due to the chelating effect of sodium citrate was controlled by calcium chloride administration, adjustment of blood separation rates, and reduction of the blood-to-citrate ratio. This report demonstrates that intensive, large-volume plasma separation for long periods of time can be achieved safely in critically ill patients without serious adverse effects.
Factor structure of the Yale-Brown Obsessive-Compulsive Scale: a two dimensional measure.
The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS: Goodman, Price, Rasmussen, Mazure, Fleischman, Hill, Heninger & Charney, 1989a, b, Archives of General Psychiatry, 46, 1006-1016), a widely used measure of obsessions and compulsions, is typically used by summing the items to yield a global measure of symptom severity. However obsessive-compulsive disorder (OCD) is characterized by two distinct groups of symptoms (i.e. obsessions and compulsions), and so it was hypothesized that OCD, as assessed by the Y-BOCS, may be two dimensional. In other words, the items assessing obsessions may be factorially distinct from the items assessing compulsions. A confirmatory factor analysis (CFA) was conducted using responses from 83 OCD patients to determine whether OCD as assessed with the Y-BOCS is unidimensional or forms two distinct dimensions. Results supported a two-factor solution, and suggest that items assessing obsessions should be scored as one subscale, and items assessing compulsions scored as a separate subscale. Depression, as assessed by the Beck Depression Inventory, (Beck, Ward, Mendelsohn, Mock & Erbaugh, 1961, Archives of General Psychiatry, 4, 561-571), was correlated with both subscales. Trait anxiety, as assessed by the State-Trait Anxiety Inventory (Speilberger, 1983, Manual for the State-Trait Anxiety Inventory (Form Y). Palo-Alto, CA: Consulting Psychologists Press), was correlated with the obsessions subscale but not with the compulsions subscale.
The market is the message.
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Effect of vagotomy on cholecystokinin release and gallbladder contraction in patients with complicated duodenal ulcer.
In this prospective study, we investigated gallbladder (GB) contraction and plasma cholecystokinin (CCK) levels in response to food intake before and 1 month after vagotomy in 27 patients with complicated duodenal ulcer. Highly selective vagotomy (HSV) was carried out in 6 patients, truncal vagotomy and pyloroplasty (TVP) in 4, truncal vagotomy and antrectomy (TVA) in 7, selective vagotomy and pyloroplasty (SVP) in 5 and selective vagotomy and antrectomy (SVA) in another 5 patients with pyloric stenosis. The results of our studies indicated that (1) basal plasma CCK levels increased significantly after vagotomy, (2) none of the vagotomy operations altered the integrated CCK response, (3) unlike HSV, SVA and TVA, SVP and TVP decreased GB emptying and (4) antrectomy significantly enhanced CCK release after food intake. We concluded from these findings that the operative procedure of HSV, SVA or TVA to circumvent bile stasis-related postvagotomy cholelithiasis is superior to SVP or TVP in the surgical treatment of complicated duodenal ulcer.
Characterization of the insulin A-chain major immunogenic determinant presented by MHC class II I-Ad molecules.
Data are presented which demonstrate the minimal insulin peptide required to activate a large group of insulin-specific T hybrids following presentation by either live or fixed APC, is the N-terminal insulin-A(1-13) peptide. Functional activation and competition assays using both live and fixed APC with 19 synthesized variants of the N-terminal bovine insulin A-chain molecule permitted classification of peptide residues into MHC agretope and T cell epitope regions. Our findings indicate insulin A-chain peptide occupies the Ag binding groove of class II MHC in an extended conformation as a result of intracellular reduction of A-loop disulfide bonds. Insulin A-chain Cys7 and Cys11 residues represent two independent T cell epitopes N- and C-terminal to the A-loop region. Data are presented that demonstrate the unique residues associated with several insulin isoform molecules contribute to the peptide agretope region. Our findings may suggest peptide agretopes may subtly modify the peptide/MHC conformation presented to TCR.
The natural history of aortic dilatation in Marfan syndrome.
OBJECTIVES: To determine the relationship between age and aortic dilatation in patients with Marfan syndrome and to define the rate of progression of aortic dilatation in these patients. DESIGN: All patients were evaluated in a multidisciplinary clinic to establish a firm diagnosis of Marfan syndrome. Aortic dimensions were measured by echocardiography and patients with Marfan syndrome were followed up with annual physical and echocardiographic examinations to detect any change in aortic diameter over the subsequent four years. PATIENTS: One hundred and fifty-seven patients were referred to the clinic for assessment, of whom 40 exhibited diagnostic features of Marfan syndrome. Only 24 of these patients had previously been diagnosed with Marfan syndrome, while 17 other patients, previously diagnosed with Marfan syndrome, had insufficient clinical features to justify the diagnosis. RESULTS: Among the 40 patients (19 male, 21 female) with Marfan syndrome (mean age, 28 +/- 15 years), the prevalence of cardiovascular abnormalities was 90%. Aortic root dilatation was present in 78% of patients, aortic regurgitation in 28%, mitral valve prolapse in 65% and mitral regurgitation in 35%. Mean aortic root diameter in the Marfan patients (21.4 +/- 4.0 mm/m2 body surface area) markedly exceeded that of age and sex matched controls without Marfan syndrome (14.9 +/- 2.2 mm/m2) and that of first-degree relatives without Marfan syndrome (15.3 +/- 2.9 mm/m2). The occurrence of aortic dilatation in Marfan syndrome was variable, with patients as young as 20 years exhibiting severe dilatation. All patients with Marfan syndrome exhibiting aortic dilatation were advised to take beta-adrenergic blocking drugs, unless contraindicated, in an effort to retard the rate of aortic dilatation. Among 33 patients followed up for at least one year, 14 (42%) exhibited an increase in aortic diameter of at least 2 mm, while 16 of 23 patients (70%) followed up for at least three years exhibited similar progression of aortic dilatation. The overall mean rate of dilatation in the Marfan patients was 1.9 mm per year. Nine patients developed aortic dilatation of more than 50 mm diameter during four years' follow-up and required surgical repair of the aorta. Each of these patients is well at between three months' and four years' follow-up. CONCLUSIONS: Aneurysmal dilatation of the aorta is a common complication of Marfan syndrome and may become manifest at an early age. Furthermore, aortic dilatation can progress rapidly, even in the absence of symptoms. Individuals with Marfan syndrome should have annual echocardiographic examinations to monitor aortic root dimensions, and those exhibiting rapid progression of aortic dilatation or an aortic root diameter in excess of 50 mm, should be considered for elective composite graft repair of the aorta.
Retinal pigment epithelial cells modulate lymphocyte function at the blood-retina barrier by autocrine PGE2 and membrane-bound mechanisms.
Retinal pigment epithelial cells (RPE) in vitro display many characteristics typical of antigen-presenting cells (APC) yet are poor inducers of lymphocyte proliferation and in vivo appear to remain MHC class II negative within the acute inflammatory chorioretinal lesions associated with experimental autoimmune uveoretinitis. In an in vitro assay system designed to mimic the in vivo situation as closely as possible, RPE cells profoundly suppressed lymphocyte proliferation to antigen, mitogen, and IL-2 even in the presence of exogenous APC. RPE immunosuppression was found to comprise both soluble and membrane-bound components and to be reversible as lymphocytes could be restimulated by thymocytes after coculture on RPE cells. Indomethacin restored proliferative responses of cocultured lymphocytes to specific antigen and mitogen indicating that the soluble component of suppression was mediated in part by PGE2 production by the RPE cells. Constitutive production of PGE2 by RPE cells was found to be low (approximately 10(-9) M), but increased to high levels (approximately 10(-6) M) in coculture with activated lymphocytes. In addition, antigen-specific primed lymphocyte responses during coculture with RPE were enhanced in the presence of indomethacin compared to similar splenocyte responses in the absence of RPE cells. However, indomethacin did not reverse RPE inhibition of IL-2-driven lymphocyte proliferation, and the failure of lymphocyte proliferation could not be attributed to TGF beta production by RPE cells, indicating that other RPE cell-immunosuppressive mechanisms were involved. Trypsin pretreatment of RPE cell monolayers removed an as yet unidentified inhibitory factor present on the RPE cell membrane and in combination with indomethacin enabled RPE cells to function as antigen-presenting cells.
Amygdala kindling, anxiety, and corticotrophin releasing factor (CRF).
Wistar rats were kindled electrically in the anterior or posterior medial amygdala of the right hemisphere. One week after the fourth stage 5 seizure, anxiety was assessed in the elevated plus maze test. Anxiety levels of rats kindled in posterior medial amygdala were reduced relative to implanted controls, but not relative to unoperated controls. Kindling of the anterior medial amygdala increased anxiety relative to implanted and unoperated controls. The different effects of kindling on behavior were unrelated to any parameter of kindling. The stress of an ICV injection of saline increased anxiety in unkindled controls but reduced anxiety in anterior medial amygdala-kindled rats. Injection stress effects on behavior were blocked by 50 micrograms of alpha-helical CRF (the CRF receptor blocker). These findings suggest that CRF released by the stress of the injection procedure mediates the behavioral effects in both kindled and control rats. In contrast, injection of CRF (2 micrograms, ICV) has no greater effect than ICV saline in anterior medial amygdala kindled rats, whereas it was anxiogenic in unkindled rats. ICV vehicle and CRF reduce kindling-induced anxiety equally. These findings suggest that CRF released during the injection procedure saturates available CRF receptors. Finally, kindling did not alter basal plasma corticosterone levels. These and other findings suggest that the anxiety-modulating actions of CRF are at central CRF receptors.
Treatment of choroidal neovascularisation in age-related macular degeneration with interferon alfa-2a and alfa-2b.
Forty eight eyes of 42 patients with choroidal neovascular membranes and age-related macular degeneration who received three different dose regimens of systemic interferon alfa-2 were studied retrospectively. The response to treatment of 41 eyes of the 37 patients who received at least 4 weeks' treatment was analysed with respect to the change in size of the choroidal neovascular membrane and the visual acuity compared with pretreatment levels. The size of the membrane at the end of the course of treatment had decreased in seven (17%) eyes overall, not changed in 16 (39%), and increased in 18 (44%). At the end of treatment, the visual acuity had improved in seven (17%) eyes, not changed in 27 (66%), and deteriorated in seven (17%). With an average follow up of 10 months after treatment, the visual acuity had deteriorated compared with the pretreatment value in 21 out of 41 (51%) eyes. Vision improved in some fellow eyes with disciform scars. Side effects were common and often severe. The data suggest that one of the major effects of interferon alfa may be to decrease vascular permeability. While further research may identify a place for interferon alfa in the treatment of choroidal neovascularisation, we were unable to demonstrate that the treatment regimens of systemic interferon alfa we used caused a dramatic benefit to patients with exudative age-related macular degeneration.