Search PubMed⌕ Search

Biomedical subjects

R J Wyatt

Publications and source records attributed to R J Wyatt.

At least 19 recordsLinked to original sources
PubMed2004

Pediatric IgA nephropathy: clinical features at presentation and outcome for African-Americans and Caucasians.

AIM: To determine the disease severity at onset and outcome for African-American and Caucasian pediatric patients with IgA nephropathy diagnosed at the Le Bonheur Children's Medical Center since 1990. DESIGN/METHODS: The study population included all patients diagnosed with IgA nephropathy at the Le Bonheur Children's Medical Center from January 1990 through February 2004. All were below age 18 at biopsy. Clinical features assessed at diagnosis were age, gender, presence of hypertension, history of macroscopic hematuria, degree of proteinuria, severity of renal histology and pattern for immunofluorescent reactants. STATISTICS: Student's t-test was used to compare age at biopsy and length of follow-up between the 2 groups. Fisher's exact test was used to compare features at presentation and patterns of immunofluorescence. Kidney survival was predicted by the Kaplan-Meier method. RESULTS: Forty-seven patients (17 African-American, 29 Caucasian) were studied. Clinical features at diagnosis and pattern for all immunofluorescent reactants did not differ significantly between the 2 groups. Mesangial deposition of C1q occurred in 4/17 African-Americans as compared to 1/27 Caucasians (p = 0.06). Four patients (2 African-Americans, 2 Caucasians) progressed to end-stage renal disease. Predicted kidney survival was 96% (94% in African-Americans and 97% in Caucasians) at 1 year and 91% (94% in African-Americans and 89% in Caucasians) at 5 years from diagnosis. Mean time from diagnosis to end-stage renal disease or last follow-up was 3.3 years (3.8 for African-Americans, 3.0 for Caucasians). Macroscopic hematuria occurred prior to diagnosis for 90% of the Caucasian as compared to 61% of the African-American patients (p = 0.03). Urinalysis was normal at last follow-up visit for 24% of African-American patients and 32% of Caucasian patients. CONCLUSION: In a relatively small sample from a single center, except for the difference in macroscopic hematuria, clinical features at diagnosis and outcome of IgA nephropathy appear similar for African-American and Caucasian pediatric patients.

Black or African American↗
PubMed2003

Height, weight and body mass index (BMI) in psychiatrically ill US Armed Forces personnel.

BACKGROUND: In both psychiatrically ill and psychiatrically healthy adults, the connection between health and individuals' height and weight has long been examined. Specifically, research on the idea that individuals with certain body types were prone to particular psychiatric diseases has been explored sporadically for centuries. The hypothesis that psychiatrically ill individuals were shorter and weighed less than psychiatrically healthy counterparts would correspond with the neurodevelopmental model of psychiatric disease. METHOD: To evaluate possible links between psychiatric illness and physique, the height, weight and BMI of 7514 patients and 85,940 controls were compared. All subjects were part of the National Collaborative Study of Early Psychosis and Suicide (NCSEPS). Patients were US military active duty personnel hospitalized for either bipolar disorder, major depressive disorder, or schizophrenia and controls were psychiatrically-healthy US military active duty personnel matched for date of entry into the service. RESULTS: No consistent differences in height, weight or BMI were found between patients and controls, or between patient groups. Some weak ANOVA differences were found between age at the time of entering active duty and weight, as well as BMI, but not height. CONCLUSIONS: Unlike most previous studies that have looked at the links between height and psychiatric illness, this study of the NCSEPS cohort found that, at entry into the US Armed Forces, there were no consistent decreases in height for patients with bipolar disorder, major depressive disorder or schizophrenia compared with a large control group. Furthermore, there were no consistent differences for weight or BMI.

Anthropometry↗
PubMed2001

Adverse events during a placebo phase for inpatients with chronic schizophrenia.

BACKGROUND: This report builds on a previous analysis examining the long-term effects of a placebo period on a group of inpatients with chronic schizophrenia. In the present analysis, outcome was evaluated through the use of the Psychiatric Adverse Events Rating Scale. METHODS: This retrospective analysis examined adverse events for 55 patients with chronic schizophrenia who were placed in a double-blind placebo study on the inpatient units of the National Institute of Mental Health Neuropsychiatric Research Hospital. The number and severity of adverse events experienced by these patients during baseline, placebo, and discharge periods were analyzed. RESULTS: The frequency and severity of adverse events for this group of patients were modest. Most patients did not experience a statistically significant increase in adverse events during their placebo phase; however, a subgroup of patients who were hospitalized for less than 2 months after antipsychotic medications were restored did experience a statistical elevation in adverse events, and that frequency remained statistically elevated at discharge. CONCLUSIONS: The results confirm the findings from our previous analysis. Regardless of whether outcome is measured by a behavioral rating scale or by an adverse event scale, given a sufficiently lengthy recovery period, patients with chronic schizophrenia who go through a placebo phase return to baseline.

Antipsychotic Agents↗
PubMed2001

Rationale for the study of early intervention.

Consistent but relatively weak evidence exists that treating patients with schizophrenia early in the course of their illness can decrease long-term morbidity. Relatedly, it is possible that treating individuals even earlier might produce better results. The findings presented set the stage for early and even earlier formal intervention studies, where the potential benefits are thought to outweigh the potential risks.

Antipsychotic Agents↗
PubMed2001

Fungal peritonitis caused by Curvularia species in a child undergoing peritoneal dialysis.

We report the first case of peritonitis caused by Curvularia species in a child undergoing peritoneal dialysis. He presented with gray-black proteinaceous material obstructing the lumen of his Tenckhoff catheter. Although the peritoneal fluid was cloudy, the patient suffered neither significant abdominal tenderness nor systemic symptoms. Catheter removal and treatment with amphotericin B allowed complete recovery and return to peritoneal dialysis within 7 days. Outdoor play in a wooded environment may have allowed contact of this saprophytic fungus with the child's indwelling catheter transfer set.

Amphotericin B↗
PubMed2001

Evidence-based assessment of treatment options for children with IgA nephropathies.

We present an evidence-based evaluation of published data on therapy for children with various presentations of the IgA nephropathies--idiopathic IgA nephropathy (IgAN) and Henoch-Schonlein purpura nephritis (HSPN). Particular attention has been paid to the outcome markers used in the studies reviewed, with the best evidence provided by markers highly associated with progressive renal failure. No treatment modality for either IgAN or HSPN in pediatric patients has been shown to be effective by a properly designed and administered randomized controlled trial (i.e., the highest level of evidence--level 1). Lower levels of evidence support the use of a variety of corticosteroid regimens, often in combination with other agents, although there are some conflicting studies in this area. No convincing evidence has been published to date to support the use of fish oil, angiotensin-converting enzyme inhibitors or tonsillectomy for the treatment of children with IgAN or HSPN. Well designed randomized controlled trials in children with the IgA nephropathies need to be undertaken.

Adult↗
PubMed2001

Lithium revisited: savings brought about by the use of lithium, 1970-1991.

BACKGROUND: Recent estimates of the cost of manic-depressive illness totaled roughly $45 billion in 1991. Using data from the Epidemiological Catchment Area (ECA) study, this study estimates the savings brought about by the use of lithium between 1970 and 1991. METHODS: Total savings are the difference between estimated actual costs and projected costs had lithium never been introduced. Actual yearly costs were interpolated from data for 1970 and 1991, and projected costs were obtained by adjusting 1970 costs with Consumer Price Index (CPI) and population inflaters. All costs for 1970 were obtained using methods almost identical to those used to calculate the 1991 costs of manic-depressive illness, presented in a previous publication. All savings are presented in 1991 dollars. RESULTS: Between 1970 and 1991, lithium saved over $170 billion, or roughly over $8 billion per year. Approximately $15 billion in direct costs, which included inpatient and outpatient care as well as research, was saved between 1970 and 1991. The savings are more dramatic for indirect costs, which include the lost productivity of wage-earners, homemakers, family caregivers, and individuals who are in institutions or who committed suicide; these totaled roughly $155 billion. CONCLUSIONS: Our results suggest that, although manic-depressive illness is still costly, lithium has been tremendously successful in treating the illness, and has provided enormous financial savings in the process.

Antimanic Agents↗
PubMed2000

Effects of smoking during antipsychotic withdrawal in patients with chronic schizophrenia.

A number of studies have shown that patients with schizophrenia smoke more than other psychiatric patients and more than the general population. Also, medicated schizophrenics who smoke present more positive symptoms of schizophrenia than non-smokers. The objective of the present study was to assess the effect of smoking on ratings of psychopathology for 30 days following discontinuation of antipsychotic medication. The subjects were 101 treatment-resistant patients with schizophrenia who had been admitted to the inpatient service of Neuroscience Research Hospital (NRH), National Institute of Mental Health, between 1982 and 1994 to undergo studies involving discontinuation of antipsychotic medication. Patients were rated independently on a daily basis on the 22-item Psychiatric Symptom Assessment Scale (PSAS), an extended version of the Brief Psychiatric Rating Scale (BPRS). At baseline, ratings for Verbal Positive, Paranoia and Loss of Function were higher in smokers (n=65) than non-smokers (n=36), but a statistically significant difference was observed only for the Verbal Positive cluster. Analysis by gender revealed that male non-smokers had the lowest psychopathology ratings at baseline. There were no differences in Anxiety/depression, Behavior Positive, Deficit Symptoms or Mannerisms (a measure for abnormal involuntary movements). Following medication discontinuation, repeated-measure analysis demonstrated a 'time' effect for all the variables studied and a 'group' (smokers vs. non-smokers) effect for Verbal Positive, Paranoia, and Loss of Function. Post-hoc comparisons at individual time points showed significantly higher ratings for smokers at week 1 for Paranoia. No differences were observed at later time points. In conclusion, at baseline, smokers had more positive symptoms and were apparently more functionally impaired than non-smokers. This difference was no longer evident after a 30 day medication discontinuation period.

Adult↗
PubMed2000

6-(18)F-DOPA PET study in patients with schizophrenia. Positron emission tomography.

Presynaptic dopamine metabolism was studied in a group of patients with schizophrenia and in an age- and gender-matched normal control group using 6-[(18)F]fluoro-L-DOPA ((18)F-DOPA) and positron emission tomography (PET). Nineteen patients, nine drug-free, 10 on neuroleptics, and 13 normal control subjects underwent PET scans using (18)F-DOPA. The neuroleptic-treated patients were taking typical neuroleptics (N=4) or the atypical neuroleptic, clozapine (N=6). The ratio of specific/non-specific activity was calculated for eight cortical and subcortical regions of interest. Medication-free patients had a significant reduction in (18)F-DOPA uptake in the ventral striatum (P=0.04) and significantly increased uptake in the posterior cingulate (P=0.02) compared with normal control subjects. The 18F-DOPA PET technique proved to be useful and sensitive in detecting changes in dopamine metabolism in patients with schizophrenia in vivo. The results of this study provide evidence of an aberrant dopamine system in schizophrenia.

Adult↗
PubMed2000

Penny-wise and pound-foolish: the impact of measurement error on sample size requirements in clinical trials.

BACKGROUND: Clinical research studies must compensate for measurement error by increasing the number of subjects that are studied, thereby increasing the financial costs of research and exposing greater numbers of subjects to study risks. In this article, we model the relationship between reliability and sample-size requirements and consider the potential tangible cost savings resulting from the decreased number of subjects needed when reliability of raters is improved or multiple ratings are used. METHODS: Standard methods are used to model reliability based on the intraclass correlation coefficient (R) and to perform power calculations. The impact of multiple raters on reliability for a given baseline level of reliability is modeled according to the Spearman Brown formula. RESULTS: Our models demonstrate that meaningful reductions in sample size requirements are gained from improvements in reliability. For example, improving reliability from R = .7 to R = .9 will decreases sample size requirements by 22%. Reliability is improved by training and by the use of the mean of multiple ratings. For example, if the reliability of a single rating is 0.7, the reliability of the mean of two ratings will be 0.8. CONCLUSIONS: The costs to improve reliability either through rater training efforts or use of the mean of multiple ratings is cost effective because of the consequent reduction in number of subjects needed. Efforts to improve reliability and thus reduce subject requirements in a study also may lead to fewer patients bearing the burden of research participation and to a shortening of the duration of studies.

Clinical Trials as Topic↗
PubMed2000

In vivo PET studies of the dopamine D2 receptors in rhesus monkeys with long-term MPTP-induced parkinsonism.

Studies of dopamine (DA) receptor binding in early parkinsonian patients, or in models of Parkinson's disease, have revealed a supersensitivity of the D2-like receptor subtype as compared to age-matched controls. The lack of upregulation in advanced patients is often attributed to the effects of prolonged antiparkinsonian therapy, but the impact of therapy vs. intrinsic mechanisms in untreated patients or animals with long-term lesions of the DA nigrostriatal pathway has been difficult to address. We studied, in vivo, by PET using the DA D2 receptor ligand raclopride, the status of the DA receptors in normal rhesus monkeys and those with acute (3 months) or long-term (10 years) MPTP-induced nigrostriatal lesions. Compared to age-matched controls, there was no change in raclopride binding in MPTP-treated animals without parkinsonian symptoms. There was a significant increase in raclopride binding in the putamen (but not caudate nucleus) of all the animals displaying rigidity, hypo- and bradykinesia. This increase was greater in the animals with acute lesions (32%) than with established, long-term lesions (18%). There was no correlation between the postmortem striatal DA concentrations and in vivo raclopride binding but there was a correlation between PET raclopride binding and [(3)H]raclopride binding in vitro. Complex changes in D2 receptor binding occur in various stages of parkinsonism. Antiparkinsonian therapy is unlikely to be solely responsible for the lack of upregulation found in advanced parkinsonian patients but may be a contributing factor.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Dopamine induces cell death, lipid peroxidation and DNA base damage in a catecholaminergic cell line derived from the central nervous system.

Dopamine can be autoxidized to superoxides and quinones. Superoxides can form hydroxyl radicals that are highly reactive with lipids, proteins and DNA leading to neuronal damage and cell death. We used a clonal catecholaminergic cell line (CATH.a) derived from the central nervous system to evaluate the effects of dopamine on cell death, lipid peroxidation and DNA base damage. Dopamine produces cell death in CATH.a cells and this is associated with an increase in annexin binding, which is an early indicator of apoptosis. Incubation of CATH.a cells with deferoximine, an iron chealator, partially antagonizes dopamine-induced cell death. In CATH.a cells, dopamine produces an increase in both lipid peroxidation, as measured by cis-parinaric acid fluorescence, and DNA oxidative base damage, as measured by 8-hydroxy-2'-deoxyguanosine formation. Cell death was inhibited 84-92% by the hydrophilic antioxidants, dithiothreitol, L-cysteine, and N-acetylcysteine. The lipophilic vitamins, retinol and vitamin E and the vitamin E analog, Trolox, inhibited dopamine-induced cell death by 18-33%. The lipophilic antioxidants probucol, propyl glycol and butylated hydroxyanisone had no inhibitory effect on dopamine-induced cell death. These data suggest that damage to DNA and lipids may be partially responsible for dopamine-induced cell death in CATH.a cells.

Journal Article↗
PubMed2000

IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23.

End-stage renal disease (ESRD) is a major public health problem, affecting 1 in 1,000 individuals and with an annual death rate of 20% despite dialysis treatment. IgA nephropathy (IgAN) is the most common form of glomerulonephritis, a principal cause of ESRD worldwide; it affects up to 1.3% of the population and its pathogenesis is unknown. Kidneys of people with IgAN show deposits of IgA-containing immune complexes with proliferation of the glomerular mesangium (Fig. 1). Typical clinical features include onset before age 40 with haematuria and proteinuria (blood and protein in the urine), and episodes of gross haematuria following mucosal infections are common; 30% of patients develop progressive renal failure. Although not generally considered a hereditary disease, striking ethnic variation in prevalence and familial clustering, along with subclinical renal abnormalities among relatives of IgAN cases, have suggested a heretofore undefined genetic component. By genome-wide analysis of linkage in 30 multiplex IgAN kindreds, we demonstrate linkage of IgAN to 6q22-23 under a dominant model of transmission with incomplete penetrance, with a lod score of 5.6 and 60% of kindreds linked. These findings for the first time indicate the existence of a locus with large effect on development of IgAN and identify the chromosomal location of this disease gene.

Chromosome Mapping↗
PubMed2000

The design of the prenatal determinants of schizophrenia study.

This paper describes the Prenatal Determinants of Schizophrenia (PDS) Study; three companion papers report the first results. The PDS Study was designed to study early antecedents of schizophrenia in a birth cohort of 1959-1967 for whom a wealth of archived prenatal data--including maternal sera--was available. Making use of the registries of a health plan into which the cohort was born, we ascertained and then diagnosed 71 cases of schizophrenia and spectrum disorders in the cohort. We describe herein the available prenatal data, the process of case diagnosis, and the strategies used to analyze prenatal determinants of schizophrenia in this cohort. Data are presented that bear on the main sources of potential bias and are important to understanding the strengths and limitations of this unique data set.

Adult↗
PubMed2000

Maternal prepregnant body mass and risk of schizophrenia in adult offspring.

This study examined the relation between maternal prepregnant body mass index (BMI) and development of schizophrenia and schizophrenia spectrum disorders in adult offspring from the Prenatal Determinants of Schizophrenia Study. The study drew on a previously studied cohort of births occurring between 1959 and 1967 to women enrolled in a prepaid health plan. Computerized treatment registries were used to identify possible cases of schizophrenia and spectrum disorders in adult offspring belonging to the health plan from 1981 to 1997. Diagnostic interviews and medical record reviews resulted in diagnosis of 63 cases of schizophrenia and spectrum disorders; these cases and 6,570 unrelated and unaffected cohort members whose mothers also had prepregnancy measures of BMI comprised the sample for analyses. High (> or = 30.0), compared with average (20.0-26.9), maternal prepregnant BMI (kg/m2) was significantly associated with schizophrenia and spectrum disorders in the adult offspring (relative risk [RR] = 2.9; 95% confidence interval [CI] 1.3-6.6), independently of maternal age, parity, race, education, or cigarette smoking during pregnancy. Low (< or = 19.9) maternal BMI was not associated with schizophrenia and spectrum disorders (RR = 1.2; 95% CI 0.64-2.2). Future studies of this cohort will examine factors that may help explain the relationship of high maternal prepregnant BMI with schizophrenia, including nutritional and metabolic factors, toxic exposures, and obstetrical complications.

Adolescent↗
PubMed2000

Maternal exposure to respiratory infections and adult schizophrenia spectrum disorders: a prospective birth cohort study.

We sought to examine the relationship between maternal exposure to adult respiratory infections and schizophrenia spectrum disorder (SSD) in the Prenatal Determinants of Schizophrenia (PDS) Study, a large birth cohort investigation. Previous work suggests that second trimester exposure to respiratory infection may be a risk factor for SSD. We therefore examined whether this class of infection was associated with adult SSD. For this purpose, we capitalized on several design advantages of the PDS Study, including a comprehensive, prospective data base on physician-diagnosed infections and a continuous followup in which diagnoses of SSD were made, in the majority, by face-to-face interview. Second trimester exposure to respiratory infections was associated with a significantly increased risk of SSD, adjusting for maternal smoking, education, and race (rate ratio [RR] = 2.13 [1.05-4.35], chi2 = 4.36, df= 1,p = 0.04); no associations were shown for first trimester and third trimester exposure to these respiratory infections. These findings support-and extend-previous studies suggesting that second trimester respiratory infections are risk factors for SSD. This study therefore has implications toward uncovering the etiology of schizophrenia and developing preventive strategies.

Adult↗
PubMed2000

Incidence and cumulative risk of treated schizophrenia in the prenatal determinants of schizophrenia study.

The present study uses data from the Prenatal Determinants of Schizophrenia (PDS) Study to derive age- and sex-specific estimates of incidence and cumulative risk for DSM-IV schizophrenia. Although not designed as an incidence study, the PDS Study uses both a well-defined population under continuous followup and DSM-IV diagnoses. The originating cohort was established in Alameda County, California, during 1959-1967 and yielded 12,094 cohort members followed from 1981 to 1997 during the principal ages at risk for schizophrenia. Survival analytic techniques showed that schizophrenia incidence rates per 10,000 person-years for men were 9.4 for ages 15-19; 5.6 for ages 20-24; 3.3 for ages 25-29; and 0.9 for ages 30-34. Schizophrenia incidence rates per 10,000 person-years for women were 1.6 for ages 15-19; 1.3 for ages 20-24; and 4.1 for ages 25-29. The cumulative risk for schizophrenia by age 38 was 0.93 percent for men and 0.35 percent for women. These estimates of incidence rates and risk were higher than those in traditional incidence studies but similar to recent findings in other cohorts. Possible explanations for the apparently high rates of disorder include chance, design effects, and true variation in risk over time and place.

Adolescent↗