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Biomedical subjects

E Jamieson

Publications and source records attributed to E Jamieson.

At least 19 recordsLinked to original sources

Vascularized tissue-engineered chambers promote survival and function of transplanted islets and improve glycemic control.

We have developed a chamber model of islet engraftment that optimizes islet survival by rapidly restoring islet-extracellular matrix relationships and vascularization. Our aim was to assess the ability of syngeneic adult islets seeded into blood vessel-containing chambers to correct streptozotocin-induced diabetes in mice. Approximately 350 syngeneic islets suspended in Matrigel extracellular matrix were inserted into chambers based on either the splenic or groin (epigastric) vascular beds, or, in the standard approach, injected under the renal capsule. Blood glucose was monitored weekly for 7 weeks, and an intraperitoneal glucose tolerance test performed at 6 weeks in the presence of the islet grafts. Relative to untreated diabetic animals, glycemic control significantly improved in all islet transplant groups, strongly correlating with islet counts in the graft (P<0.01), and with best results in the splenic chamber group. Glycemic control deteriorated after chambers were surgically removed at week 8. Immunohistochemistry revealed islets with abundant insulin content in grafts from all groups, but with significantly more islets in splenic chamber grafts than the other treatment groups (P<0.05). It is concluded that hyperglycemia in experimental type 1 diabetes can be effectively treated by islets seeded into a vascularized chamber functioning as a "pancreatic organoid."

Animals↗

The population health perspective as a framework for studying child maltreatment outcomes.

The population health perspective (PHP) is commonly used in addressing a wide range of health issues. This article examines the strengths and limitations of the perspective. The determinants of health that are an integral part of the PHP are used as a framework in considering the range of outcomes associated with exposure to child maltreatment. Directions for further research are outlined.

Child↗

Activation of Fas and caspase 3 precedes PrP accumulation in 87V scrapie.

The sequence of events involved in the neurodegeneration caused by transmissible spongiform encephalopathies is not yet known. Using a murine scrapie model in which neurodegeneration in the hippocampus is restricted to the CA2, we show an up-regulation of the proapoptotic markers Fas and caspase 3 early in the incubation period prior to disease-specific prion protein (PrP) deposition and clinical signs. These results suggest that activation of Fas and caspase 3 are involved in the early pathological sequence of events during murine scrapie, and that these proapoptotic markers may be a specific method for early detection of neurodegeneration.

Animals↗

Changing a single amino acid in the N-terminus of murine PrP alters TSE incubation time across three species barriers.

The PrP gene of the host exerts a major influence over the outcome of transmissible spongiform encephalopathy (TSE) disease, but the mechanism by which this is achieved is not understood. We have introduced a specific mutation into the endogenous murine PrP gene using gene targeting to produce transgenic mice with a single amino acid alteration (proline to leucine) at amino acid position 101 in their PrP protein (P101L). The effect of this alteration on incubation time, targeting and PrP(Sc) formation has been studied in TSE-infected animals. Transgenic mice carrying the P101L mutation in PrP have remarkable differences in incubation time and targeting of central nervous system pathology compared with wild-type littermates, following inoculation with infectivity from human, hamster, sheep and murine sources. This single mutation can alter incubation time across three species barriers in a strain-dependent manner. These findings suggest a critical role for the structurally 'flexible' region of PrP in agent replication and targeting of TSE pathology.

Amino Acid Sequence↗

Apoptosis and dendritic dysfunction precede prion protein accumulation in 87V scrapie.

The sequence of events involved in the neurodegeneration caused by transmissible spongiform encephalopathies (TSEs) is not yet known. Using a murine scrapie model in which neurodegeneration in the hippocampus is restricted to CA2, we show that pyramidal neuron damage and death by an apoptotic mechanism occur early in the incubation period, prior to the appearance of CA2 disease-specific accumulation of PrP and the onset of clinical disease. We suggest that the initial hippocampal pathological event in this model is dendritic dysfunction and activation of an apoptotic pathway rather than PrP accumulation.

Animals↗

Childhood abuse and lifetime psychopathology in a community sample.

OBJECTIVE: The authors assessed lifetime psychopathology in a general population sample and compared the rates of five psychiatric disorder categories between those who reported a childhood history of either physical or sexual abuse and those who did not. METHOD: A modified version of the Composite International Diagnostic Interview and a self-completed questionnaire on child abuse were administered to a probability sample (N=7,016) of Ontario residents 15 to 64 years of age. RESULTS: Those reporting a history of childhood physical abuse had significantly higher lifetime rates of anxiety disorders, alcohol abuse/dependence, and antisocial behavior and were more likely to have one or more disorders than were those without such a history. Women, but not men, with a history of physical abuse had significantly higher lifetime rates of major depression and illicit drug abuse/dependence than did women with no such history. A history of childhood sexual abuse was also associated with higher rates of all disorders considered in women. In men, the prevalence of disorders tended to be higher among those who reported exposure to sexual abuse, but only the associations with alcohol abuse/dependence and the category of one or more disorders reached statistical significance. The relationship between a childhood history of physical abuse and lifetime psychopathology varied significantly by gender for all categories except for anxiety disorders. Although not statistically significant, a similar relationship was seen between childhood history of sexual abuse and lifetime psychopathology. CONCLUSIONS: A history of abuse in childhood increases the likelihood of lifetime psychopathology; this association appears stronger for women than men.

Adolescent↗

A single amino acid alteration in murine PrP dramatically alters TSE incubation time.

In order to investigate mutations linked to human TSEs, we have used the technique of gene targeting to introduce specific mutations into the endogenous murine PrP gene which resulted in a P101L substitution (Prnp(a101L)) in the murine PrP gene. This mutation is equivalent to the 102L mutation in the human PrP gene which is associated with Gerstmann-Sträussler syndrome. Since the mutated gene is in the correct chromosomal location and control of the mutant gene expression is identical to that of the wild type murine PrP gene, the precise effect of the 101L mutation in the uninfected and TSE infected mouse can be investigated in this transgenic model. Mice homozygous for this mutation (101LL) while showing no spontaneous TSE disease were more susceptible to TSE disease than wild type mice following inoculation with GSS infectivity. Disease was transmitted from these mice to mice both with and without the Prnp(a101L) allele. The 101L mutation does not therefore produce spontaneous genetic disease in mice but does dramatically alter incubation periods following TSE infection. Additionally, a rapid TSE transmission was demonstrated associated with extremely low amounts of PrP(Sc).

Amino Acid Substitution↗

Trends in special (high-security) hospitals. 1: Referrals and admissions.

BACKGROUND: Special hospitals in England provide psychiatric care and treatment in high security. Their future is often questioned. AIMS: To test for variation in demand for high-security psychiatric services over one 10-year period. METHOD: This study was from the special hospitals' case registers and hospital records. The main measures were numbers and annual rates for referrals and beds offered; the Mental Health Act 1983 (MHA) classification of mental disorder; adjusted population rates by health region; admission episodes; legal category of detention; admission source and type of offence. RESULTS: Referrals to special hospitals showed no decrease during the 10 years; an apparent increase may reflect underrecording before 1992. Admissions fell by about 16% over the 10 years, but with regional variation. Women, civil cases, admissions under the MHA classifications of psychopathic disorder or mental impairment and directly from a court on a hospital order were most affected. There was an increase in admissions of pre-trial and sentenced male prisoners, and of transferred hospital order patients from other hospitals. CONCLUSIONS: There is continuing demand from all parts of the country for high-security hospital beds. The smaller numbers admitted appear to include more demanding cases.

Commitment of Persons with Psychiatric Disorders↗

Trends in special (high-security) hospitals. 2: Residency and discharge episodes, 1986-1995.

BACKGROUND: It has been argued that many patients in special hospital beds do not need to be there. In the 1990s there were initiatives to discharge women and people with learning difficulties. AIMS: To test for trends in special hospital discharges and to examine annual resident cohorts. METHOD: This study was from case registers and hospital records. The main measures were numbers and annual rates for referrals and beds offered; the Mental Health Act 1983 (MHA) classification of mental disorder; adjusted population rates by region; admission episodes; legal category of detention; admission source and type of offence. RESULTS: The median annual number of residents was 1859 (range 1697-1910), with an 8% fall for the period. This particularly affected people in mental impairment categories. Numbers were sustained in the male mental illness groups. Discharges, mainly to other institutions, increased. There was no overall change over the 10 years in length of stay for treatment, but successive admission cohorts from 1986 did show some reduction, even with solely remand order cases excluded. CONCLUSIONS: Service planners need a longitudinal perspective on service use. Trends over 10 years to both fewer admissions and more discharges have reduced the special hospital population, but despite new treatments for schizophrenia, men under mental illness classification, as well as transfer from other secure settings, have gone against this trend.

Female↗

A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy.

A mutation equivalent to P102L in the human PrP gene, associated with Gerstmann-Straussler syndrome (GSS), has been introduced into the murine PrP gene by gene targeting. Mice homozygous for this mutation (101LL) showed no spontaneous transmissible spongiform encephalopathy (TSE) disease, but had incubation times dramatically different from wild-type mice following inoculation with different TSE sources. Inoculation with GSS produced disease in 101LL mice in 288 days. Disease was transmitted from these mice to both wild-type (226 days) and 101LL mice (148 days). In contrast, 101LL mice infected with ME7 had prolonged incubation times (338 days) compared with wild-type mice (161 days). The 101L mutation does not, therefore, produce any spontaneous genetic disease in mice but significantly alters the incubation time of TSE infection. Additionally, a rapid TSE transmission was demonstrated despite extremely low levels of disease-associated PrP.

Alleles↗

Implicit and explicit memory in children with traumatic brain injury.

This study aimed to investigate whether implicit memory is preserved in children with traumatic brain injury (TBI). A fragmented picture-completion procedure (Snodgrass, Smith, Feenan, & Corwin, 1987) was used to compare implicit and explicit memory of 12 children with severe long-term TBI and 12 controls, matched for age and gender. On the implicit memory task, both the TBI and control groups were found to show significant priming. In addition, the extent of priming for the two groups was not found to be different. On the explicit memory task, however, the TBI group was found to perform significantly more poorly than the control group. These results are consistent with those reported in the adult TBI literature and have implications for understanding and rehabilitating memory impairments in children with TBI.

Adolescent↗

Age-of-onset classification of conduct disorder: reliability and validity in a prospective cohort study.

OBJECTIVE: To test in a prospective clinical cohort study the reliability and validity of the age-of-onset subtyping of conduct disorder. METHOD: Participants were adolescents referred to psychiatric clinics who met DSM-III-R criteria for conduct disorder by structured diagnostic interview. Age of onset was the reported age of the first conduct disorder symptom. The reliability of age-of-onset report was tested by assessing agreement within informant on interviews 2 to 4 weeks apart. Age-of-onset groups were compared within informant on rates of correlates and symptom and social functioning outcomes over a period of 3 years. RESULTS: The reliability of age-of-onset report was low (kappa of 0.1 and 0.4 by adolescent and parent informant, respectively). Although the early-onset group had elevated rates of attention-deficit/hyperactivity disorder, family disadvantage, and aggressive and nonaggressive antisocial behaviors at inclusion, growth curve analysis showed that age-of-onset subtyping had no predictive validity. CONCLUSIONS: The reliability of ascertainment of age of onset of antisocial behavior requires further study. While age-of-onset subtyping has heuristic value with respect to the study of the causal pathways to conduct disorder, it is premature to use this system in clinic settings.

Adolescent↗

Route of discharge for special (high-security) hospital patients with personality disorder. Relationship with re-conviction.

BACKGROUND: A considerable proportion of patients with personality disorder are discharged directly to the community from special (high-security) hospitals. AIMS: To examine whether patients with personality disorder discharged directly to the community are more likely to be re-convicted than those transferred to psychiatric hospitals of lesser security. METHOD: Re-conviction data for a five- to nine-year follow-up were collected for a four-year (1988-1991) special hospital discharge cohort of patients with personality disorder. RESULTS: Individuals discharged directly to the community were not significantly more likely to be re-convicted than those transferred to less secure psychiatric hospitals. However, patients discharged to the community without formal conditions of supervision were more likely to be re-convicted than those discharged to the community with conditions or those transferred to other psychiatric hospitals. CONCLUSIONS: Formal supervision after discharge may be more important than actual destination in influencing the likelihood of re-conviction.

Adult↗

Surviving social assistance: 12-month prevalence of depression in sole-support parents receiving social assistance.

BACKGROUND: Although it is generally recognized that poverty and depression can coexist among single parents receiving social assistance, there is insufficient research on this topic. The goals of this study therefore were to investigate the prevalence, correlates and health care expenditures associated with depression among sole-support parents receiving social assistance. METHODS: Sole-support parents who had applied for social assistance in 2 regions of southwestern Ontario were included in the study. Depression was diagnosed with the 1994 University of Michigan Composite International Diagnostic Interview short forms. RESULTS: The 12-month prevalence rate of depressive disorder among the parents interviewed was 45.4% (345/760). A total of 247 (32.5%) had major depressive disorder alone, 19 (2.5%) had dysthymia, and 79 (10.4%) had both major depressive disorder and dysthymia ("double depression"). Those with major depressive disorder, particularly double depression, had significantly higher rates of coexisting psychiatric disorder than those without depressive disorders. Parents with depression reported higher rates of developmental delay and behaviour problems in their children than parents without depression. Expenditures for health care services were higher for parents with depression and for their children than for parents without depressive disorder and their children. INTERPRETATION: Single parents receiving social assistance have high rates of depression. Such parents with depression also have higher rates of other psychiatric disorders and higher expenditures for health care services, and their children have higher rates of developmental delay and behaviour problems.

Adaptation, Psychological↗

Progenitor-cell mobilization after low-dose cyclophosphamide and granulocyte colony-stimulating factor: an analysis of progenitor-cell quantity and quality and factors predicting for these parameters in 101 pretreated patients with malignant lymphoma.

PURPOSE: To define parameters that predict for rapid engraftment after peripheral-blood stem-cell (PBSC) transplantation, progenitor thresholds, the proportion of patients who achieve these thresholds with a standardized mobilization regimen, and the factors that predict for mobilization efficiency. PATIENTS AND METHODS: One hundred and one patients with pretreated lymphoma were mobilized with cyclophosphamide 1.5 g/m2 and granulocyte colony-stimulating factor (G-CSF), with the first apheresis performed when the recovery WBC count was > or = 5.0 x 10(9)/L. The relationship between the number of progenitor cells collected and patient age, sex, diagnosis, prior radiotherapy, and time since last chemotherapy was determined by multivariate analysis. The relationship between these factors, progenitor numbers returned, post-PBSC G-CSF, and hematologic recovery was performed in 81 patients following chemotherapy with carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM protocol). RESULTS: No BEAM recipients had delayed neutrophil recovery beyond 28 days. Delayed platelet recovery occurred in 7.4% and minimum and optimum thresholds of 1 x 10(6) and 3.5 x 10(6) CD34+ cells/kg and 1 x 10(5) and 3.5 x 10(5) granulocyte-macrophage colony-forming cells (GM-CFC)/kg were established. Hematologic recovery was adversely affected by prior treatment with mini-BEAM, and neutrophil recovery was accelerated by post-PBSC G-CSF. The minimum GM-CFC threshold was achieved with a single apheresis in 83% of patients and in 90% with two aphereses. The optimal threshold was achieved with two leukaphereses in 69% of patients. Prior radiotherapy adversely affected mobilization. CONCLUSION: Hematopoietic recovery following PBSC is dependent on progenitor-cell number infused and affect of previous chemotherapy on progenitor quality. Progenitor-cell mobilization is adversely affected by prior radiotherapy. The minimum threshold of GM-CFC required is achieved in most patients with a single apheresis, but an optimal collection usually requires at least two harvests.

Adolescent↗

Self-reported cardiovascular disease and risk factors. Prevalence in Ontario among women 50 and older.

OBJECTIVE: To determine the prevalence of self-reported cardiovascular disease and risk factors among Ontario women aged 50 and older. DESIGN: Analysis of the 1990 Ontario Health Survey, a population-based, cross-sectional survey. SETTING: Ontario communities. PARTICIPANTS: Residents of Ontario communities during 1990 who responded to the 1990 Ontario Health Survey (61,239 respondents in 35,479 households), weighted to represent the population of Ontario. MAIN OUTCOME MEASURES: Reported heart disease, hypertension, diabetes, height and weight, physical activity, and smoking habits. RESULTS: Nearly 11% of women aged 50 and older report "heart disease"; 24.9% hypertension, and 5.4% diabetes. Women were less likely than men to smoke daily, to smoke 25 or more cigarettes a day, and to be overweight, but were more likely to have lower levels of physical activity. CONCLUSIONS: The prevalence of self-reported heart disease and medical and lifestyle risk factors for heart disease is relatively high among Ontario women aged 50 and older. Physicians and public health officials must keep women in mind when designing or implementing programs or services for heart disease.

Cardiovascular Diseases↗

Peripheral blood stem cell support does not accelerate haemopoietic recovery from miniBEAM chemotherapy.

Intermediate-dose salvage therapy is frequently given for relapsed and resistant lymphomas and is usually intensely myelosuppressive. In an attempt to reduce the haematological toxicity of miniBEAM, one of the commonly used salvage regimens, peripheral blood stem cell (PBSC) support was given to 21 consecutive patients who received miniBEAM chemotherapy. The outcome was compared with a non-randomised control group of consecutive patients who were similar to the supported group apart from the fact that it was not possible to collect PBSC before miniBEAM therapy. Apart from a small, marginally significant difference between the supported and unsupported groups in the number of days for which intravenous antibiotics were required, there were no other differences between the two groups in supportive care required and times to haematological recovery. In conclusion, PBSC support does not accelerate haematological recovery from miniBEAM therapy.

Adolescent↗

Childhood sexually transmitted diseases and child sexual abuse: results of a Canadian survey of three professional groups.

The purpose of this national survey was to determine the knowledge and attitudes of Canadian health and social services professionals about the occurrence of sexually transmitted diseases (STDs) in children and its implications for child sexual abuse. A mailed questionnaire was sent to a randomly selected sample of 4,500 nurses, physicians, and youth/social workers across the country. Response rates varied from over 60% of nurses and youth/social workers to only 38% of the physicians. Nurses and youth/social workers were younger than physicians, had a proportionately higher number of females within their groups, and more frequently reported that they had or might have been sexually abused as children. Although there was no statistically significant difference among the groups on the composite knowledge score, physicians scored higher than the other two groups on knowledge about STDs, and youth/social workers had the highest knowledge scores about sexual abuse. Some differences in attitudes among the groups were also noted. Overall, the rates of respondents reporting confidence in their ability to treat children with STDs or child sexual abuse were low (26% and 35% respectively). This paper presents the overall results of the survey, and makes recommendations for strategies to enhance professional expertise in the area.

Adolescent↗