Showing papers by "Sunnybrook Health Sciences Centre published in 1998"

Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries.

Abstract: Background: The purpose of this study was to determine the prevalence, cause, severity, and patterns of associated injuries of limb peripheral nerve injuries sustained by patients with multiple injuries seen at a regional Level 1 trauma center. Methods: Patients sustaining injuries to the radial, median, ulnar, sciatic, femoral, peroneal, or tibial nerves were identified using a prospectively collected computerized database, maintained by Sunnybrook Health Science Centre, and a detailed chart review was undertaken. Results: From a trauma population of 5,777 patients treated between January 1, 1986, and November 30, 1996, 162 patients were identified as having an injury to at least one of the peripheral nerves of interest, yielding a prevalence of 2.8%. These 162 patients sustained a total of 200 peripheral nerve injuries, 121 of which were in the upper extremity. The mean patient age was 34.6 years (SEM ± 1.1 year), and 83% of patients were male. The mean injury severity score was 23.1 (±0.90), and the mean length of hospital stay was 28 days (±1.8). Conclusions: Motor vehicles crashes predominated (46%) as the cause of injury. The most frequently injured nerve was the radial nerve (58 injuries), and in the lower limb, the peroneal nerve was most commonly injured (39 injuries). Diagnosis of a peripheral nerve injury was made within 4 days of admission to Sunnybrook Health Science Centre in 78% of the cases. Surgery was required to treat 54% of patients. Head injuries were the most common associated injury, occurring in 60% of patients. Other common associated injuries included fractures and dislocations. The present report aims to aid in identification and treatment of peripheral nerve injuries.

The Treatment of Unrelated Disorders in Patients with Chronic Medical Diseases

Abstract: Background Patients can have several illnesses concurrently, yet some of these diseases may be neglected if one problem consumes attention. We conducted a population-based analysis in Ontario, Canada — where universal health insurance is provided — to determine whether unrelated disorders are less likely to be treated in patients with chronic diseases. Methods We studied the 1,344,145 residents of Ontario in 1995 who were 65 or older and eligible to receive prescription medications free of charge as part of the Ontario Drug Benefit program. Patients with diabetes mellitus were identified by prescriptions for insulin, pulmonary emphysema by prescriptions for ipratropium bromide, and psychotic syndromes by prescriptions for haloperidol. For each chronic disease, we selected an unrelated treatment: estrogen-replacement therapy for patients with diabetes mellitus, lipid-lowering medications for those with pulmonary emphysema, and medical treatment of arthritis for those with psychotic syndromes. Results The 3...

Cell adhesion and the integrin-linked kinase regulate the LEF-1 and beta-catenin signaling pathways.

Abstract: The integrin-linked kinase (ILK) is an ankyrin repeat containing serine-threonine protein kinase that can interact directly with the cytoplasmic domains of the β1 and β3 integrin subunits and whose kinase activity is modulated by cell–extracellular matrix interactions. Overexpression of constitutively active ILK results in loss of cell–cell adhesion, anchorage-independent growth, and tumorigenicity in nude mice. We now show that modest overexpression of ILK in intestinal epithelial cells as well as in mammary epithelial cells results in an invasive phenotype concomitant with a down-regulation of E-cadherin expression, translocation of β-catenin to the nucleus, formation of a complex between β-catenin and the high mobility group transcription factor, LEF-1, and transcriptional activation by this LEF-1/β-catenin complex. We also find that LEF-1 protein expression is rapidly modulated by cell detachment from the extracellular matrix, and that LEF-1 protein levels are constitutively up-regulated at ILK overexpression. These effects are specific for ILK, because transformation by activated H-ras or v-src oncogenes do not result in the activation of LEF-1/β-catenin. The results demonstrate that the oncogenic properties of ILK involve activation of the LEF-1/β-catenin signaling pathway, and also suggest ILK-mediated cross-talk between cell–matrix interactions and cell–cell adhesion as well as components of the Wnt signaling pathway.

The Sunnybrook Stroke Study A Prospective Study of Depressive Symptoms and Functional Outcome

Abstract: Background and Purpose—To assess the prevalence of depressive symptoms, their clinical correlates, and the effects of depressive symptoms on stroke recovery, a relatively unselected, well-diagnosed cohort of consecutive stroke survivors was followed prospectively. Methods—Consecutive admissions to a regional stroke center who met World Health Organization and National Institute of Neurological Disorders and Stroke criteria for stroke were eligible. Subarachnoid hemorrhage and brain stem strokes were excluded. Patients underwent CT, single-photon emission CT, and standardized neurological and cognitive examinations at entry. At 3 months and 1 year after stroke, depressive symptoms were assessed with the Montgomery Asberg Depression Rating Scale (MADRS) and the Zung Self-Rating Depression Scale (SDS). Functional outcome was measured with the Functional Independence Measure, and handicap was assessed by the Oxford Handicap Scale. Results—We assessed 436 patients at entry (mean±SD age, 74.9±11.6 years). There...

Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase

Abstract: Telomeric DNA of mammalian chromosomes consists of several kilobase-pairs of tandemly repeated sequences with a terminal 3' overhang in single-stranded form. Maintaining the integrity of these repeats is essential for cell survival; telomere attrition is associated with chromosome instability and cell senescence, whereas stabilization of telomere length correlates with the immortalization of somatic cells. Telomere elongation is carried out by telomerase, an RNA-dependent DNA polymerase which adds single-stranded TAGGGT repeats to the 3' ends of chromosomes. While proteins that associate with single-stranded telomeric repeats can influence tract lengths in yeast, equivalent factors have not yet been identified in vertebrates. Here, it is shown that the heterogeneous nuclear ribonucleoprotein A1 participates in telomere biogenesis. A mouse cell line deficient in A1 expression harbours telomeres that are shorter than those of a related cell line expressing normal levels of A1. Restoring A1 expression in A1-deficient cells increases telomere length. Telomere elongation is also observed upon introduction of exogenous UP1, the amino-terminal fragment of A1. While both A1 and UP1 bind to vertebrate single-stranded telomeric repeats directly and with specificity in vitro, only UP1 can recover telomerase activity from a cell lysate. These findings establish A1/UP1 as the first single-stranded DNA binding protein involved in mammalian telomere biogenesis and suggest possible mechanisms by which UP1 may modulate telomere length.

Impact of oncogenes in tumor angiogenesis: Mutant K-ras up-regulation of vascular endothelial growth factor/vascular permeability factor is necessary, but not sufficient for tumorigenicity of human colorectal carcinoma cells

Abstract: Targeted disruption of the single mutant K-ras allele in two human colorectal carcinoma cell lines (DLD-1 and HCT-116) leads to loss of tumorigenic competence in nude mice with retention of ability to grow indefinitely in monolayer culture. Because expression of the mutant K-ras oncogene in these cell lines is associated with marked up-regulation of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), we sought to determine whether this potent angiogenesis inducer plays a role in K-ras-dependent tumorigenic competence. Transfection of a VEGF121 antisense expression vector into DLD-1 and HCT-116 cells resulted in suppression of VEGF/VPF production by a factor of 3- to 4-fold. The VEGF/VPF-deficient sublines, unlike the parental population or vector controls, were profoundly suppressed in their ability to form tumors in nude mice for as long as 6 months after cell injection. In contrast, in vitro growth of these sublines was unaffected, thus demonstrating the critical importance of VEGF/VPF as an angiogenic factor for HCT-116 and DLD-1 cells. Transfection of a full-length VEGF121 cDNA into two nontumorigenic mutant K-ras knockout sublines resulted in a weak but detectable restoration of tumorigenic ability in vivo in a subset of the transfectants, with no consistent change in growth properties in vitro. The findings indicate that mutant ras-oncogene-dependent VEGF/VPF expression is necessary, but not sufficient, for progressive tumor growth in vivo and highlight the relative contribution of oncogenes, such as mutant K-ras, to the process of tumor angiogenesis.

Analysis of mammographic density and breast cancer risk from digitized mammograms.

Abstract: To evaluate the association between mammographic density and breast cancer risk, a simple, observer-assisted technique called interactive thresholding was developed that allows reliable quantitative assessment of mammographic density with use of a computer workstation. Use of this technique helps confirm that mammographic density is one of the strongest risk factors for breast cancer and is present in a large proportion of breast cancer cases. The strong relationship between mammographic density and breast cancer risk suggests that the causes of breast cancer may be better understood by identifying the factors associated with mammographically dense tissue and determining how such tissue changes as these factors vary. Furthermore, because it can be modified, mammographic density may also be a good vehicle for the development and monitoring of potential preventive strategies. Areas of ongoing investigation include evaluating a potential genetic component of mammographic density by comparing density measurements in twins and understanding changes in density relative to age, menopausal status, exogenous hormone use, and exposure to environmental carcinogens. In addition, work is ongoing to establish measurements from imaging modalities other than mammography and to relate these measurements directly to breast cancer risk.

Measuring patient satisfaction with anesthesia care: a review of current methodology.

Abstract: I n clinical settings such as anesthesia, using patient satisfaction as an indicator to monitor the quality of clinical care has potential merit. For patients, satisfaction represents, at least in theory, an evaluation of the healthcare experience based on their own values, perceptions, and interactions with the healthcare environment. For healthcare providers, patient satisfaction can be used to assess the actual impact of healthcare processes on the patients themselves. Patients’ ratings of their satisfaction can reflect many facets of care not easily examined in any other manner: compassionate bedside skills, efficient attendance to needs, participation in decision-making, and adequate communication and information (1). An ideal measure of patient satisfaction could therefore provide unique feedback on the quality of practice for medical specialties such as anesthesia. A renewed focus has been sought for patient satisfaction as a clinical end point and a quality indicator of anesthesia care. Previous studies have demonstrated the limitations of using adverse anesthetic events to monitor anesthesia care (2). Major outcomes (death and complications such as myocardial infarction, cardiac arrest, and severe brain injury) are too rare to allow useful comparisons among institutions. Assessing minor outcomes (such as pain and nausea) pose significant methodological problems of uncertain case mix, inconsistent reporting compliance, imprecise definitions, and underand overreporting. Orkin et al. (3) emphasized the still unproven relationships between most intermediate events (for example, transient intraand postoperative hypoxemia) and clinically significant adverse events (death, myocardial infarction, etc.), as well as the difficulties in establishing those relationships. They also suggested that, in light of the

OCI-5/GPC3, a Glypican Encoded by a Gene That Is Mutated in the Simpson-Golabi-Behmel Overgrowth Syndrome, Induces Apoptosis in a Cell Line–specific Manner

Abstract: OCI-5/GPC3 is a member of the glypican family. Glypicans are heparan sulfate proteoglycans that are bound to the cell surface through a glycosyl-phosphatidylinositol anchor. It has recently been shown that the OCI-5/GPC3 gene is mutated in patients with the Simpson-Golabi-Behmel Syndrome (SGBS), an X-linked disorder characterized by pre- and postnatal overgrowth and various visceral and skeletal dysmorphisms. Some of these dysmorphisms could be the result of deficient growth inhibition or apoptosis in certain cell types during development. Here we present evidence indicating that OCI-5/GPC3 induces apoptosis in cell lines derived from mesothelioma (II14) and breast cancer (MCF-7). This induction, however, is cell line specific since it is not observed in NIH 3T3 fibroblasts or HT-29 colorectal tumor cells. We also show that the apoptosis-inducing activity in II14 and MCF-7 cells requires the anchoring of OCI-5/GPC3 to the cell membrane. The glycosaminoglycan chains, on the other hand, are not required. MCF-7 cells can be rescued from OCI-5/GPC3–induced cell death by insulin-like growth factor 2. This factor has been implicated in Beckwith-Wiedemann, an overgrowth syndrome that has many similarities with SGBS. The discovery that OCI-5/GPC3 is able to induce apoptosis in a cell line– specific manner provides an insight into the mechanism that, at least in part, is responsible for the phenotype of SGBS patients.

Gender Differences in Adverse Drug Reactions

Abstract: The objective of this study is to identify gender-related differences in the types of symptoms and drugs reported to cause an adverse drug reaction. Patient data from the Sunnybrook Health Science Centre ADR Clinic for the period from April 1986 to May 1996 were reviewed. Of the 2,367 patients assessed, 74.1% were female. The mean age of the patients was 43 +/- 17 years. Drug classes most frequently reported to elicit an adverse event were general antiinfectives (60.4%), nervous system agents (21.5%), and musculoskeletal agents (3.7%). Skin-related reactions accounted for 49.0% of all reported adverse drug reactions. More than one agent was reported to be responsible for the adverse drug reaction(s) in 50% of the female patients, versus 33.1% of all male patients. Of the female patients, 47.6% were referred for skin or oral challenge testing, versus 41.6% of the male patients. Of the female patients, 6.2% tested positive to the agent compared with 6.1% of all male patients. These results support previous findings that female gender is a risk factor for the development of adverse drug reactions. Further work is required to elucidate the mechanisms explaining the differences observed between male and female patients.

The fall and rise of carotid endarterectomy in the United States and Canada.

Abstract: Background Randomized clinical trials have demonstrated the efficacy of carotid endarterectomy in the prevention of stroke when the procedure is performed in regional centers of surgical excellence. However, the relative effects of these studies on the rates of carotid endarterectomy in the United States and Canada have been unclear. Methods We calculated the annual rate of carotid endarterectomy in the U.S. states of California and New York and in the Canadian province of Ontario from 1983 through 1995. We also studied whether patients in the early 1990s were selectively referred to hospitals with high volumes of procedures and historically low in-hospital mortality rates. Results Rates of carotid endarterectomy fell in all three regions from 1984 to 1989 (from 126 to 66 per 100,000 adults 40 years of age or older in California, from 65 to 40 per 100,000 in New York, and from 40 to 15 per 100,000 in Ontario), after the publication of studies demonstrating that the rates of complications of carotid endart...

Brain-behavior correlations in hemispatial neglect using CT and SPECT The Sunnybrook Stroke Study

Abstract: Objective: Structural and functional lesion localization in patients with hemispatial neglect. Design: Location and severity of brain damage on CT and SPECT correlated with neglect performance as assessed with a battery of drawings, line bisection, and line and shape cancellation subtests. Patients: Participants included 120 consecutive stroke patients with a single right-hemisphere-damaged lesion on CT who were admitted to the Acute Stroke Care Unit at Sunnybrook Health Science Centre. Of these, 88 also had a SPECT. Results: On CT, 82 patients with neglect (compared with 38 without neglect) had more extensive damage in the parietal and sensorimotor cortex and white matter fiber bundles, including the posterior-superior longitudinal and inferior-frontal fasciculi ( p p p Conclusions: Damage in the parietal and anterior cingulate cortex and posterior white matter fiber bundles correlated with hemispatial neglect. Combining structural- and functional-imaging techniques with neurobehavioral analysis can elucidate brain-behavior relationships.

The economic cost of musculoskeletal disorders in Canada

Abstract: Objective This study estimated the total cost of musculoskeletal disorders for Canadians in 1994 and assessed the sensitivity of these cost estimates to variations in the definition of musculoskeletal disorders Methods Disease-related costs, from a societal perspective, were measured using a prevalencebased analysis First, direct treatment costs, including expenditures on hospitals and other institutions, physicians and other health professionals, drugs, research, and other items were assessed Second, indirect costs associated with lost (or foregone) productivity due to disability and premature mortality were evaluated using the human capital approach Results The total cost of musculoskeletal disorders in Canada was $256 billion (in 1994 Canadian dollars, $100 CDN ≈ $075 US) or 34% of the gross domestic product Direct and indirect costs were estimated at $75 billion and $181 billion, respectively Lower and upper bound estimates of the total cost of musculoskeletal disorders, derived from the sensitivity analysis, were $199 billion and $308 billion, respectively Wide variations were reported in the total cost of various musculoskeletal disorder subcategories, with the highest costs reported for injuries ($107 billion), back and spine disorders ($81 billion), and arthritis and rheumatism ($59 billion) Conclusions The economic cost of musculoskeletal disorders was substantial and was sensitive to the definition of musculoskeletal disorders and other underlying assumptions The hallmark of this study was the variation between subcategories in their cost, pattern of health resource use, and sequelae The cost estimates may provide guidance in setting priorities for research and prevention activities

Scaphoid nonunion with avascular necrosis of the proximal pole : Treatment with a vascularized bone graft from the dorsum of the distal radius

Abstract: Scaphoid nonunion with avascular necrosis of the proximal pole remains a difficult problem. We have endeavoured to heal the fracture, restore scaphoid height and revascularize the proximal pole of the scaphoid by means of a vascularized dorsal interposition graft from the distal radius. The procedure has resulted in union of six of ten fractures. Fractures that healed had not been treated by a previous bone grafting procedure. Dissatisfaction was due to loss of motion in patients who had healed fractures, and pain in those patients with persistent non-unions.

Establishing a link between oncogenes and tumor angiogenesis.

Abstract: We have tried to stress that mutant oncogenes or overexpressed, nonmutated proto-oncogenes, in addition to their direct affect on promoting aberrant tumor cell proliferation (and survival), may possess a crucial indirect means of stimulating tumor cell growth through regulation of angiogenesis. This effect would never be observed in tissue culture studies of oncogene function using pure cultures of tumor cells, which probably helps explain why the pro-angiogenic function of oncogenes has not been appreciated until only relatively recently. Indeed, the very first indication of a possible contributory role of oncogenes, such as ras and myc, to tumor angiogenesis was first reported by Thompson et al. in 1989, who used reconstituted organ cultures of the mouse prostate gland for their studies (69). This potentially important contribution of oncogenes to tumor growth and development may prove to have an impact on how various signal transduction inhibitors that are now in early phase clinical trials, e.g., monoclonal neutralizing antibodies to the human EGF receptor (70), function in vivo as anti-tumor agents.

Antiepileptic drug hypersensitivity syndrome.

Abstract: The antiepileptic drug hypersensitivity syndrome (AHS) is an adverse drug reaction associated with the aromatic antiepileptic drugs (AEDs) phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and primidone. The syndrome is defined by the triad of fever, skin rash, and internal organ involvement. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, terbinafine, azathioprine, and allopurinol. Diagnosis of AHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic, or collagen vascular disorders. The incidence is approximately 1 in 3,000 exposures. AHS starts with fever, rash, and lymphadenopathy, within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis, and myostitis. AHS is associated with a relative excess of reactive oxidative metabolites of the AED. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Crossreactivity among PHT, CBZ, and PB is as high as 70-80%.

Axonal injury and the neuropathology of shaken baby syndrome

Abstract: We examined an autopsy series of 14 children with shaken baby syndrome (SBS) who lacked skull fracture. Evidence of axonal injury was sought using immunohistochemical stains for neurofilament, 68-kDa neurofilament and beta-amyloid precursor protein (betaAPP). BetaAPP-positive axons were present in the cerebral white matter of all cases of SBS but were also present in 6 of 7 children dying of non-traumatic hypoxic ischemic encephalopathy (HIE). Swollen axons were present in 11 of 14 cases of SBS and in 6 of 7 cases of HIE. BetaAPP-positive axons were present in both groups in the midbrain and medulla. The cervical spinal cord in SBS contained betaAPP-positive axons in 7 of 11 cases; 5 of 7 contained swollen axons within the white matter tracts; in 2 immunoreactivity was localized to spinal nerve roots; in all 7 there was a predilection for staining at the glial head of the nerve root. Among cases of HIE, none showed abnormal axons or betaAPP-positive reactivity in the cervical cord white matter. We conclude that cerebral axonal injury is common in SBS, and may be due in part to hypoxic/ischemic injury. Cervical cord injury is also common, and cannot be attributed to HIE. These findings corroborate suggestions that flexion-extension injury about the cervical spinal column may be important in the pathogenesis of SBS.

The effects of focal and diffuse brain damage on strategy application: Evidence from focal lesions, traumatic brain injury and normal aging

Abstract: A new test of strategy application was designed to be relatively free of the constraints that limit the standard neuropsychological assessment of supervisory abilities. The validity of the test was assessed in 3 samples of participants with varying degrees of supervisory deficits and frontal systems dysfunction: focal frontal lesions, traumatic brain injury (TBI), and normal aging. Inefficient strategy application varied systematically across the 3 groups and was not due to extraneous factors such as forgetting the test instructions. Previous case studies have emphasized strategy application deficits in the face of normal neuropsychological test performance. In this study, it was shown that strategically impaired participants from a consecutive series can include those both with and without deficient neuropsychological test performance. When neuropsychological impairment was present, it was greatest on executive functioning tasks. Among participants with nonstrategic performance, there was evidence for a dissociation of knowledge from action. This finding was not specific to focal frontal lesions. A number of supervisory processes contributing to strategy application were identified. Exploratory analyses indicated differential effects of lesion location on these processes, especially inferior medial frontal and right hemisphere lesions. Overall, the results supported the use of unstructured tasks in the assessment of supervisory abilities. (JINS, 1998, 4, 247–264.)

Mammographic densities and breast cancer risk

Abstract: Variations between individuals in the radiographic appearance, or mammographic pattern, of the female breast arise because of differences in the relative amounts and X-ray attenuation characteristics of fat and connective and epithelial tissue. Studies using quantitative methods of assessment have consistently shown these variations to be strongly related to risk of breast cancer. Individuals with extensive areas of radiologically dense breast tissue on the mammogram have been found to have a risk of breast cancer that is four to six times higher than women with little or no density. In this paper, we propose a model for the relationship of mammographic densities to risk of breast cancer. We propose that the risk of breast cancer associated with mammographically dense breast tissue is due to the combined effects of two processes: cell proliferation (mitogenesis), induced by growth factors and sex hormones and influenced by reproductive risk factors for breast cancer; and damage to the DNA of dividing cells (mutagenesis) by mutagens generated by lipid peroxidation. We review the evidence that each of these processes is associated with mammographic densities and propose further work that we believe should be done to clarify these relationships.

Testing internal consistency and construct validity during evaluation of performance in a patient simulator.

Abstract: The primary goal of this study was to test the items in a rating system developed to evaluate anesthesiologists' performance in a simulated patient environment.A secondary goal was to determine whether the test scores could discriminate between resident and staff anesthesiologists. Two 5-item clinical scenarios included patient evaluation and induction and maintenance of anesthesia. Rating scales were no response to the problem (score = 0), compensating intervention (score = 1), and corrective treatment (score = 2). Internal consistency was estimated using Cronbach's coefficient alpha. Scores between groups were compared using the Cochran-Mantel-Haenszel test. Subjects consisted of 8 anesthesiology residents and 17 university clinical faculty. The Cronbach's coefficient alpha was 0.27 for Scenario A and 0.28 for Scenario B. Two items in each scenario markedly decreased internal consistency. When these four items were eliminated, Cronbach's coefficient alpha for the remaining six items was 0.66. Faculty anesthesiologists scored higher than residents on all six items (P < 0.001). A patient simulator-based evaluation process with acceptable reliability was developed. Implications: The reliability of anesthesia clinical performance in a patient simulation environment was assessed in this study. Of 10 items, 4 were poor in the evaluation process. When these items were removed, the reliability of the instrument improved to a level consistent with other studies. Because faculty scored higher than resident anesthesiologists, the instrument also showed discriminant validity. (Anesth Analg 1998;86:1160-4)

Lack of association between outcome measures of nerve regeneration.

Abstract: Studies of nerve regeneration in rodents utilize at least one of three classes of outcome measures: electrophysiology, morphometry, and functional tests. The assumption that these measures are correlated was tested utilizing a data set of 16 variables. Significant correlations (Spearman's rho, P ⩽ 0.05) were found within variable classes; however, none were found between classes. The three commonly utilized outcome measures do not measure the same phenomenon but rather discrete aspects of nerve regeneration. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:1095–1097, 1998.

Efficacy and safety of neuroleptics in behavioral disorders associated with dementia.

Abstract: Background Neuroleptics are commonly used to treat behavioral disorders associated with dementia. However, their safety and efficacy have not been well established in these patients. Method A meta-analysis of randomized, controlled (either placebo or active drug), double-blind trials published since 1966 (N = 16; 499 treated, 112 active controls, and 123 placebo) was conducted. Data were collected on proportion of patients with clinically significant improvement, significant side effects, and dropout rates. Results Pooled mean percentages of patients who improved (95% CI): all neuroleptics, 64% (54% to 74%); low potency, 63% (54% to 72%); moderate potency, 70% (56% to 85%); moderate-high potency, 62% (49% to 75%); and high potency, 69% (49% to 90%). Thus, no differences in efficacy existed between different potencies of neuroleptics. Therapeutic effect (neuroleptic minus placebo) was only 26% (14% to 38%). Treatment-emergent side effects were more common for neuroleptics vs. placebo (mean difference = 25%, 13% to 37%), but pooled mean dropout rates were not different (mean difference = 4%, -7% to 14%). Neither weighting by clinical trial quality (3 raters; weighted agreement, 83% to 92%) nor exclusion of poor quality trials changed the results. Conclusion Neuroleptics have small but significant efficacy over placebo in this population, and the efficacy rate is equivalent to the side effect rate. Comparing different neuroleptics shows they have similar efficacy, side effects, and dropout rates. Further study to determine more specific drug-responsive behaviors is needed to maximize benefits of these drugs.

Time and temperature dependence of MR parameters during thermal coagulation of ex vivo rabbit muscle

Abstract: Detailed measurements of the T1-weighted, T2-weighted, and MT-weighted signal were performed for ex vivo muscle samples heated to various temperatures for different times. Consistent, monotonic increases in signal intensity were observed with progressive thermal coagulation, corresponding to an increase in T2 relaxation time and an increase in MT-weighted signal for temperatures above 60°C. The relationship for T1 relaxation was more complex, showing a decrease in T1 relaxation from 40 to 60°C and an increase above 60°C. These techniques provide a more direct measure of tissue thermal coagulation than that provided by MR thermometry and suggest MR imaging strategies for the optimization and monitoring of thermal coagulation therapy protocols that create thermal damage in target tissues.

Adherence to pharmacologic management of hypertension

Abstract: Adherence to pharmacologic therapy of hypertension is low (in the range of 50-70%) and has important implications both for blood pressure control and cardiovascular complications. Based on a review of the literature using the levels of evidence grading technique, determinants of adherence to the pharmacologic therapy of hypertension have been assessed. Additionally, interventions to improve compliance were evaluated. Patient-centred, health care provider-centred and drug-specific factors have all been shown to affect adherence rates. We conclude that the extent of adherence to pharmacologic therapy is modifiable. Measurable improvements in adherence can be obtained from simplified medication regimens and a combination of behaviour strategies, including the tailoring of pill-taking to patients' daily habits and rituals, the advocacy of self-monitoring of pills and blood pressure, and the institution of reward systems.