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Biomedical subjects

G N Smith

Publications and source records attributed to G N Smith.

At least 19 recordsLinked to original sources
PubMed2006

The incidence of schizophrenia in European immigrants to Canada.

OBJECTIVE: The risk for schizophrenia in immigrants to Europe is approximately three times that of native-born populations. Discrimination and marginalization may influence the risk for schizophrenia within migrant populations. The primary objective of the present study was to determine whether the risk associated with migration was also evident 100 years ago. A second objective was to determine whether changing social stresses are associated with changes to the incidence of schizophrenia. METHOD: During the first two decades of the twentieth century, the Provincial Mental Hospital was the sole provider of psychiatric services in British Columbia, Canada. Detailed clinical records have been preserved for 99.5% of 2477 patients who had a psychiatric admission between 1902 and 1913. Diagnoses were made after a detailed file review and 807 patients met DSM-IV criteria for first-episode schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychosis not otherwise specified. Diagnoses had high inter-rater reliability. The incidence of schizophrenia in migrants from Britain or Continental Europe was compared with that in the Canadian-born population using indirect standardization and Poisson models. RESULTS: Migration from Britain or Continental Europe to Canada in the early twentieth century was associated with an increased rate of schizophrenia; IRR=1.54, (95% CI=1.33-1.78). Incidence increased over time in immigrants but not in the native-born population and this increase occurred during a period of economic recession. CONCLUSIONS: Migration was a risk factor for schizophrenia a century ago as it is today. This risk occurred in white migrants from Europe and increased during a period of increased social stress.

Adolescent↗
PubMed2006

Reduced anterior internal capsule and thalamic volumes in first-episode psychosis.

BACKGROUND: The thalamus is the gateway for sensory and motor information en route to the cortex. Information is processed via thalamocortical and corticothalamic pathways coursing through the internal capsules. In this study, we investigated the relationship between the anterior limb of the internal capsule, posterior limb of the internal capsule, and thalamus in first-episode psychosis (FEP). METHODS: Twenty-nine FEP subjects (26 DSM-IV schizophrenia, 2 schizoaffective disorder, 1 psychosis not otherwise specified) and 22 healthy volunteers participated in this study. Anterior limb of the internal capsule (AIC), posterior limb of the internal capsule (PIC), and the thalamus volumes were manually determined from MRI scans. RESULTS: FEP subjects had reduced AIC volumes (F(1,45)=6.18, p=0.017) and thalamic volumes (F(1,45)=8.00, p=0.007) compared to healthy volunteers. PIC volumes did not differ. Significant correlations between AIC volumes and thalamic volumes were observed in subjects with FEP, but not in healthy volunteers. Negative relationships between thalamic volumes and symptom severity were also observed. CONCLUSIONS: The AIC and thalamic volumes were reduced in subjects with FEP compared to healthy volunteers. Abnormalities in thalamocortical and orticothalamic pathways may contribute to functional disruption of neural circuits in psychosis.

Adolescent↗
PubMed2005

Tracing the origins of "fetal origins" of adult diseases: programming by oxidative stress?

Too small size at birth (due to poor fetal growth and/or preterm delivery) has been associated with substantially elevated risks of the metabolic syndrome (dislipidemia, insulin resistance, hypertension), type 2 diabetes and cardiovascular disease in adulthood. The mechanisms of such "fetal origins" or "programming" of disease phenomenon remain unresolved. Too large size at birth seems also associated with an increased risk. Many known or suspected causes of or conditions associated with adverse (poor or excessive) fetal growth or preterm birth have been associated with oxidative stress. Plausibly, oxidative stress may be a common link underlying the superficial "programming" associations between adverse fetal growth or preterm birth and elevated risks of certain chronic diseases. The mechanisms of oxidative stress programming may be through directly modulating gene expression or indirectly through the effects of certain oxidized molecules. Experimental investigations have well demonstrated the role of redox balance in modulating gene expression, and recent studies indicate that both the insulin functional axis and blood pressure could be sensitive targets to oxidative stress programming. Adverse programming may occur without affecting fetal growth, but more frequently among low birth weight infants merely because they more frequently experienced known or unknown conditions with oxidative insults. As oxidative stress levels are easily modifiable during pregnancy and early postnatal periods (which are plausible critical windows), the hypothesis, if proved valid, will suggest new measures that could be very helpful on fighting the increasing epidemic of the metabolic syndrome, type 2 diabetes and cardiovascular disease. Currently, there are several ongoing large randomized trials of antioxidant supplementation to counter oxidative stress during pregnancy for the prevention of preeclampsia. It would be invaluable if long-term follow-ups of infants born to women in such trials could be realized to test the oxidative stress programming hypothesis in such experimental trial settings.

Birth Weight↗
PubMed2005

Maternal cardiac autonomic function and fetal heart rate in preeclamptic compared to normotensive pregnancies.

BACKGROUND: Preeclampsia during pregnancy increases a woman's risk of cardiovascular disease in two ways. Women who develop preeclampsia are at increased risk for the development of hypertension and cardiovascular disease later in life. As well, fetal adaptations (e.g., growth restriction) may lead to the development of cardiovascular risk factors (e.g., obesity, increased cholesterol) in the offspring. Although atypical maternal cardiac autonomic function has been reported in preeclampsia, to date, its effects on fetal cardiac function have not been determined. PURPOSE: To characterize the pattern of short-term maternal cardiac autonomic modulation and spontaneous fetal heart rate changes in preeclamptic compared to normotensive women and to determine the relationship between them. METHOD: Twenty-seven mother-fetal pairs (n = 9 preeclamptic, n = 18 normotensive) at 32 to 40 weeks gestation were tested on one occasion. Maternal autonomic modulation of heart rate was measured for 20 minutes using electrocardiographic and beat-by-beat arterial systolic blood pressure recordings. Simultaneously, spontaneous fetal heart rate was obtained using a cardiotachograph. Women's cardiac autonomic responses to orthostatic stress were obtained for five minutes in a standing position. RESULTS: Comparisons of maternal cardiac measures in the preeclamptic versus the normotensive group showed that the preeclamptic group had a decreased parasympathetic nervous system indicator and an increased sympathetic nervous system indicator with increasing gestation. In response to orthostatic stress, women in both groups showed a similar increase in arterial systolic blood pressure and a decrease in parasympathetic nervous system indicator and R-R interval when standing compared to lying. Fetuses in the normotensive compared to the preeclamptic group had more spontaneous fetal heart rate accelerations; the greater the decrease in the parasympathetic nervous system indicator from lying to standing, the greater the number of fetal heart rate accelerations. CONCLUSIONS: These findings serve to further our understanding of the cardiovascular pathophysiology of preeclampsia in both the mother and the fetus. Women who develop preeclampsia during pregnancy show atypical autonomic nervous system modulation of heart rate that is associated with a decrease in spontaneous fetal heart rate accelerations in late gestation. Implications for cardiovascular nursing practice include the monitoring of maternal cardiac autonomic function during pregnancy, especially during standing, as well as a need for continued surveillance of maternal cardiovascular function following pregnancy. The negative effect on fetal heart rate accelerations has implications for the interpretation of standardized obstetrical tests of fetal well-being.

Adult↗
PubMed2004

Neuropsychological correlates of the PANSS Cognitive Factor.

OBJECTIVE: Factor analytic studies of the Positive and Negative Syndrome Scale (PANSS) have consistently isolated a factor that is frequently labeled as 'cognitive'. The present study sought to further explore the factor by examining the relationships between 4 versions of the cognitive factor and a set of neuropsychological tests. METHOD: Thirty-seven inpatients diagnosed with schizophrenia or schizoaffective disorder were assessed with the PANSS and neuropsychological measures. RESULTS: Verbal intelligence and verbal memory were found to be most closely associated with cognitive factor scores. A global rating of illness severity showed greater relationships to cognitive variables than any cognitive factor. CONCLUSIONS: The PANSS cognitive factor may reflect verbal ability and memory, but is not sufficiently comprehensive to be considered as a replacement for direct assessment of cognitive functioning.

Adolescent↗
PubMed2003

Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins.

Schizophrenia unfolds during the late period of brain maturation, while myelination is still continuing. In the present study, we used MRI and T2 relaxation analysis to measure the myelin water fraction in schizophrenia. In schizophrenia (n=30) compared with healthy subjects (n=27), overall white matter showed 12% lower myelin water fraction (P=0.031), with the most prominent effects on the left genu of the corpus callosum (36% lower, P=0.002). The left anterior genu was affected in both first-episode (P=0.035) and chronic patients (P=0.011). In healthy subjects, myelin water fraction in total white matter and in frontal white matter increased with age, and with years of education, indicating ongoing maturation. In patients with schizophrenia, neither relation was statistically significant. Post-mortem studies of anterior frontal cortex demonstrated less immunoreactivity of two oligodendrocyte-associated proteins in schizophrenia (2',3'-cyclic nucleotide 3'-phosphodiesterase by 33%, P=0.05; myelin-associated glycoprotein by 27%, P=0.14). Impaired myelination in schizophrenia could contribute to abnormalities of neural connectivity and persistent functional impairment in the illness.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2003

Effects of hypoxia on heme oxygenase expression in human chorionic villi explants and immortalized trophoblast cells.

Although hypoxia induces heme oxygenase (HO)-1 protein and mRNA expression in many cell types, hypoxia has also been shown to decrease HO-1 mRNA and protein expression. We tested the hypothesis that 24-h preexposure to hypoxia in human placental preparations suppresses HO protein expression and enzymatic function. Immortalized HTR-8/SVneo first-trimester trophoblast cells and explants of normal human chorionic villi (CV) from term placentas were cultured for 24 h in 1%, 5%, or 20% O(2). HO protein levels were determined by Western blot analysis, and microsomal HO activity was measured. HO-2 protein content was decreased by 17% and 5% in human trophoblast cells after 24-h exposure to 1% and 5% O(2), respectively, versus 20% O(2). In contrast, HO-2 protein content in CV explants was unaffected by changes in oxygenation. HO-1 protein content, which was barely detectable in both biological systems, was not affected by changes in oxygenation. Similarly, HO enzymatic activity was unchanged in both preparations after 24-h exposure to 1%, 5%, or 20% O(2). The above data do not support the hypothesis that hypoxia in the human placenta suppresses both HO protein content and HO protein function. The present observations reinforce the necessity to determine both HO protein expression and function.

Blotting, Western↗
PubMed2003

Effect of glucose and oxygen deprivation on heme oxygenase expression in human chorionic villi explants and immortalized trophoblast cells.

Although hypoxia induces heme oxygenase (HO)-1 mRNA and protein expression in many cell types, recent studies in our laboratory using human placental tissue have shown that a preexposure to hypoxia does not affect subsequent HO enzymatic activity for optimized assay conditions (20% O2; 0.5 mM NADPH; 25 microM methemalbumin) or HO-1 protein content. One of the consequences of impaired blood flow is glucose deprivation, which has been shown to be an inducer of HO-1 expression in HepG2 hepatoma cells. The objective of the present study was to test the effects of a 24-h preexposure to glucose-deprived medium, in 0.5 or 20% O2, on HO protein content and enzymatic activity in isolated chorionic villi and immortalized HTR-8/SVneo first-trimester trophoblast cells. HO protein content was determined by Western blot analysis, and microsomal HO enzymatic activity was measured by assessment of the rate of CO formation. HO enzymatic activity was increased (P < 0.05) in both placental models after 24-h preexposure to glucose-deficient medium in 0.5 or 20% O2. Preexposure (24 h) in a combination of low O2 and low glucose concentrations decreased the protein content of the HO-1 isoform by 59.6% (P < 0.05), whereas preexposure (24 h) to low glucose concentration alone increased HO-2 content by 28.2% in chorionic villi explants (P < 0.05). In this preparation, HO enzymatic activity correlated with HO-2 protein content (r = 0.825). However, there was no correlation between HO-2 protein content and HO enzymatic activity in HTR-8/SVneo trophoblast cells preexposed to 0.5% O2 and low glucose concentration for 24 h. These findings indicate that the regulation of HO expression in the human placenta is a complex process that depends, at least in part, on local glucose and oxygen concentrations.

Cell Hypoxia↗
PubMed2003

Outcome measurement in pharmacological trials: validity of the Routine Assessment of Patient Progress (RAPP).

The assessment of outcomes after treatment with antipsychotic medication is fundamental to clinical care and research. The Routine Assessment of Patient Progress (RAPP) is a reliable multidimensional scale that employs nurses' ratings of symptoms and functioning in psychiatric inpatients. The present study sought to extend validity evidence for the RAPP by examining its ability to reflect changes associated with treatment by antipsychotic medications. The use of a different sample in this study also provided the opportunity to replicate earlier validity data collected on the original set of patients. Ninety-seven separate trials were conducted, involving 65 consecutive admissions to a unit that specializes in the assessment and treatment of patients with long standing severe psychiatric disorders. The RAPP, along with the Positive and Negative Syndrome Scale and global measures of severity, were administered at baseline and at the end of each trial. Both factor scores and clinically-derived subscales were analysed for sensitivity to change. Patients were globally rated as improved, unchanged or worsened at the end of the medication trial. Results indicated that the RAPP factor, clinical scale and total scores compared favourably to other outcome measures in patients rated as improved or worse. In patients rated as unchanged, RAPP scores displayed significantly less change than did the PANSS scores. These findings support the validity of the RAPP as an outcome measure in treatment trials.

Adult↗
PubMed2002

Relationship between tissue damage and heme oxygenase expression in chorionic villi of term human placenta.

Heme oxygenase (HO) catalyzes the oxidation of heme to carbon monoxide (CO), biliverdin, and iron and is thought to play a role in protecting tissues from oxidative damage. There are three isoforms of HO: HO-1 (inducible), HO-2 (constitutive), and HO-3 (unknown function). Preeclampsia is characterized by an inadequately perfused placenta and areas of tissue damage. We hypothesized that damaged areas of placentas from women with PE and uncomplicated pregnancies are associated with an alteration in HO expression. Compared with microsomes isolated from morphologically normal and peri-infarct chorionic villi of pathological placentas, microsomes from infarcted chorionic villi from the same placentas had decreased HO activity measured under optimized assay conditions. There was no correlation between microsomal HO levels and activity and tissue damage in uncomplicated pregnancies. Whereas there was no significant difference in HO-1 protein levels across all regions of uncomplicated and mildly preeclamptic pregnancies, HO-2 protein levels were decreased (P < 0.05) in peri-infarct regions and infarcted chorionic villi of mildly preeclamptic pregnancies. Immunohistochemical analysis revealed an apparent decrease in both HO-1 and HO-2 protein expression in damaged tissues. HO-1 and HO-2 were immunolocalized in the syncytiotrophoblast layer of the chorionic villi, the underlying cytotrophoblast, and in the vascular endothelium. This study suggests that the ability of the chorionic villi to oxidize heme to CO, biliverdin, and iron may be compromised in areas of tissue damage in the placenta of women with preeclampsia.

Blotting, Western↗
PubMed2002

Severity of medial meniscus damage in the canine knee after anterior cruciate ligament transection.

OBJECTIVE: To examine the relationship between the severity of cartilage damage and the severity of meniscus damage after transection of the anterior cruciate ligament (ACLT) in adult dogs. DESIGN: Data were obtained from 40 dogs which underwent ACLT and from three additional sham-operated dogs that were subjected to arthrotomy but not ligament transection. Joint pathology was analysed 12, 24 or 32 weeks after surgery. The severity of damage to the articular cartilage on the femoral condyle and tibial plateau was graded with a scoring system based on that of the Sociètè Française d'Arthroscopie and meniscus damage was graded on a 0-4 scale. RESULTS: No damage to the meniscus or articular cartilage was observed 12 weeks after surgery in the dogs subjected only to arthrotomy. In contrast, tears of the medial meniscus were observed in two of 10 (20%) dogs examined 12 weeks after ACLT. The incidence of severe tears increased to 86% and 84% after 24 weeks and 32 weeks, respectively. Damage to the lateral meniscus was mild, with only 7.5% of all dogs with a cruciate-deficient knee having a bucket handle or complete tear. Most of the unstable knees exhibited ulceration of the articular cartilage of the femoral condyles and tibial plateaus 12 weeks (mean chondropathy score+/-standard deviation 11.9+/-8.5, N=10), 24 weeks (7.9+/-5.0, N=7), and 32 weeks (7.1+/-5.5, N=23) after ACLT. The mean chondropathy scores for the tibial plateaus were similar to those for the femoral condyles. No correlation was apparent between the severity of cartilage damage and of meniscus damage for either joint surface. CONCLUSION: Damage to the medial meniscus is a consistent feature of the pathology which develops in the canine knee after ACLT, but the severity of cartilage damage is not correlated with the severity of meniscal damage.

Animals↗
PubMed2001

Low birthweight in schizophrenia: prematurity or poor fetal growth?

In the general population, low birthweight (LBW) is associated with neurological and psychological problems during childhood and adolescence. LBW may result from premature birth or poor fetal growth, and the independent effects of these two events on childhood development are not fully understood. The rate of low weight births is increased in schizophrenia and is associated with social withdrawal during childhood and an early onset of illness. However, it is unclear whether this LBW reflects poor fetal growth or premature birth, or whether these two risk factors have distinct implications for childhood functioning and age at onset of schizophrenia. Subjects included 270 patients with schizophrenia for whom a detailed history of obstetric events could be obtained. The rate of low weight births was high and was associated with poorer premorbid functioning and an earlier age at illness onset. The rate of both premature births and poor fetal growth was high relative to the normal population. Prematurity, but not poor fetal growth, was associated with premorbid social withdrawal and an early age at illness onset. Poor fetal growth, but not prematurity, was associated with low educational achievement. These results suggest that poor fetal growth and prematurity are associated with distinct patterns of childhood maladjustment in individuals who develop schizophrenia.

Adolescent↗
PubMed2001

Endogenous carbon monoxide formation by chorionic villi of term human placenta.

Carbon monoxide (CO) is a novel messenger that is proposed to play a complementary role with nitric oxide in the regulation of placental haemodynamics. In a previous study, CO formation from exogenous haem has been measured in the microsomal fraction of chorionic villi as an index of haem oxygenase activity. The objective of the present study was to determine whether endogenous CO is formed by dissected chorionic villi of term human placenta, to which no exogenous substrate or co-factor had been added. Each sample of freshly isolated chorionic villi (approximately 0.4 g) of term human placenta from caesarean delivery was incubated in a sealed vial containing 1 ml of Krebs' solution (pH 7.4) at 37 degrees C. CO formation was determined by quantitating, using a gas-chromatographic method, the amount of CO released into the headspace gas of the incubation vial. There was time-dependent formation of endogenous CO in chorionic villi incubated at 37 degrees C during a 60-min time course. CO formation was found to be minimal in chorionic villi samples incubated at 4 degrees C and was increased relative to tissue weight. The data demonstrate that there is endogenous CO formation by chorionic villi of term human placenta.

Carbon Monoxide↗
PubMed2001

Maternal plasma homocysteine levels in women with preterm premature rupture of membranes.

Homocysteine is a sulfur-containing amino acid produced by the breakdown of methionine. Plasma homocysteine levels can be elevated due to a variety of genetic and nutritional factors. Poor nutrition from diets low in folate and vitamin B12 can lead to hyperhomocysteinemia. Mildly elevated levels of homocysteine have been implicated in a number of disease processes such as atherosclerotic vascular disease and adverse obstetrical outcomes. High levels of plasma homocysteine are also associated with abnormal collagen cross-linking. Due to homocysteine's effects on connective tissue integrity, it is hypothesized that hyperhomocysteinemia in pregnancy is associated with preterm premature rupture of membranes (PPROM). Hyperhomocysteinemia, therefore, could be a treatable cause of this important public health concern.

Amino Acid Metabolism, Inborn Errors↗
PubMed2001

Violence in treatment resistant psychotic inpatients.

This study sought to: a) ascertain the effect on rates of violence by varying its operational definition and b) compare characteristics of violent and nonviolent patients. Aggressive behavior was recorded daily for every patient (N = 78) during a 2-year period. Standardized rating scales were used to rate psychopathology and functioning. Almost two thirds of patients were aggressive to others, and 26% violently assaulted another person. Official incident reports underestimated rates of violence to others, self- harm, and property damage. Multivariate predictive models that greatly improved accuracy over base rates showed that violent patients tended to be female, schizophrenic (nonparanoid type), and abusive of alcohol before admission. Violence is more common in treatment resistant psychotic inpatients than suggested by incident reports. Standardized definitions of violence are urged in order to accurately study its prevalence and correlates. Models combining both historical/demographic and clinical data may enhance prediction of violence.

Adolescent↗
PubMed2001

Exercise-induced bronchospasm prevalence in collegiate cross-country runners.

PURPOSE: The purpose of this study was to determine the prevalence of exercise-induced bronchospasm (EIB) in collegiate cross-country runners using a protocol involving an intense exercise challenge conducted in the same environment in which the athletes train and compete. METHODS: One-hundred eighteen collegiate cross-country runners from the Los Angeles, California, metropolitan area participated in the study. All testing took place on a track at the time and location of a normal practice session. The baseline peak expiratory flow rate (PEFR) measurements (best of three) and preexercise heart rate were recorded, after which the athletes ran 2000 m on a track at 85% of maximum heart rate. The postexercise heart rate was recorded and then PEFR measurements at 2, 5, 10, and 30 min after exercise were recorded. The athletes completed a 16-item questionnaire regarding asthma symptoms and health history. Those athletes with a history of asthma and currently taking medications for the asthma were then excluded from statistical analysis of the questionnaire responses. A decrease in PEFR of 15% was considered positive for EIB. RESULTS: Of the 114 athletes not currently taking medications for asthma, at least 14% (16 athletes) were EIB positive. There was a poor correlation between reported symptoms of asthma and testing positive for EIB. CONCLUSION: This study demonstrates a high prevalence of EIB in collegiate cross-country runners (at least 14%) and that reported symptoms are a poor predictor of actual EIB.

Adolescent↗
PubMed2001

Cerebral palsy and chorioamnionitis: the inflammatory cytokine link.

Cerebral palsy remains a significant cause of perinatal morbidity in medically developed countries. Human epidemiologic data suggest a relationship between cerebral palsy and chorioamnionitis mediated by proinflammatory cytokines. This association has been confirmed by experimental data from human and animal research that demonstrate an increase in cytokine levels in the amniotic fluid of cases of white matter damage. Recent evidence suggests this damage is the result of a fetal inflammatory response initiated in response to placental inflammation. The strong association between cerebral palsy and chorioamnionitis warrants additional investigation into the mechanisms by which white matter damage is initiated and into possible neuroprotective treatments to prevent the development of cerebral palsy.

Adult↗