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T Fernandez

Publications and source records attributed to T Fernandez.

At least 19 recordsLinked to original sources
PubMed2000

Lessons from childhood-onset schizophrenia.

Childhood-onset schizophrenia (with an onset of psychosis by age 12) is a rare and severe form of the disorder which is clinically and neurobiologically continuous with the adult-onset disorder. Very early onset diseases provide an opportunity to look for more salient or striking risk or etiologic factors in a possibly more homogenous patient population. For the 47 patients with very early onset schizophrenia studied to date, there were more severe premorbid neurodevelopmental abnormalities, more cytogenetic anomalies, and potentially greater family histories of schizophrenia and associated spectrum disorders than later onset cases. There was no evidence for relatively increased obstetrical complications or environmental stress. These data, while preliminary, suggest a very early age of onset of schizophrenia may be secondary to greater genetic vulnerability. It is anticipated that future genetic studies of these patients may provide important etiologic information.

Age of Onset↗
PubMed2000

Premorbid speech and language impairments in childhood-onset schizophrenia: association with risk factors.

OBJECTIVE: As both premorbid neurodevelopmental impairments and familial risk factors for schizophrenia are prominent in childhood-onset cases (with onset of psychosis by age 12), their relationship was examined. METHOD: Premorbid language, motor, and social impairments were assessed in a cohort of 49 patients with childhood-onset schizophrenia. Familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications were assessed without knowledge of premorbid abnormalities and were compared in the patients with and without developmental impairments. RESULTS: Over one-half of the patients in this group had developmental dysfunction in each domain assessed. The patients with premorbid speech and language impairments had higher familial loading scores for schizophrenia spectrum disorders and more obstetrical complications, and their relatives had worse smooth-pursuit eye movements. The boys had more premorbid motor abnormalities, but early language and social impairments did not differ significantly between genders. There were no other significant relationships between premorbid social or motor abnormalities and the risk factors assessed here. CONCLUSIONS: Premorbid developmental impairments are common in childhood-onset schizophrenia. The rates of three risk factors for schizophrenia (familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications) were increased for the probands with premorbid speech and language impairments, suggesting that the pathophysiology of schizophrenia involves the abnormal development of language-related brain regions.

Adolescent↗
PubMed1999

Childhood-onset schizophrenia: progressive brain changes during adolescence.

BACKGROUND: Previous NIMH childhood onset schizophrenia (COS) anatomic brain MRI studies found progression of ventricular volume and other structural brain anomalies at 2-year follow up across mean ages 14 to 16 years. However, studies in adult patients generally do not show progression of ventricular volume or correlation of ventricular volume with duration of illness. To address issues of progression of brain anomalies in schizophrenia, this report extends previous studies to include a third longitudinal scan, uses a larger sample size, and includes measures of the amygdala and hippocampus. METHODS: Volumes of the total cerebrum, lateral ventricles, hippocampus, and amygdala were quantified on 208 brain magnetic resonance imaging scans from 42 adolescents with COS (23 with one or more repeat scan) and 74 age- and gender-matched controls (36 with one or more repeat scan). A statistical technique permitting combined use of cross-sectional and longitudinal data was used to assess age-related changes, linearity, and diagnostic group differences. RESULTS: Differential nonlinear progression of brain anomalies was seen during adolescence with the total cerebrum and hippocampus decreasing and lateral ventricles increasing in the COS group. The developmental curves for these structures reached an asymptote by early adulthood for the COS group and did not significantly change with age in the control group. CONCLUSIONS: These findings reconcile less striking progression of anatomic brain images usually seen for adult schizophrenia and complement other data consistent with time-limited, diagnostic-specific decreases in brain tissue. Adolescence appears to be a unique period of differential brain development in schizophrenia.

Adolescent↗
PubMed1999

Progressive cortical change during adolescence in childhood-onset schizophrenia. A longitudinal magnetic resonance imaging study.

BACKGROUND: Adolescence provides a window to examine regional and disease-specific late abnormal brain development in schizophrenia. Because previous data showed progressive brain ventricular enlargement for a group of adolescents with childhood-onset schizophrenia at 2-year follow-up, with no significant changes for healthy controls, we hypothesized that there would be a progressive decrease in volume in other brain tissue in these patients during adolescence. METHODS: To examine cortical change, we used anatomical brain magnetic resonance imaging scans for 15 patients with childhood-onset schizophrenia (defined as onset of psychosis by age 12 years) and 34 temporally yoked, healthy adolescents at a mean (SD) age of 13.17 (2.73) years at initial baseline scan and 17.46 (2.96) years at follow-up scan. Cortical gray and white matter volumes were obtained with an automated analysis system that classifies brain tissue into gray matter, white matter, and cerebrospinal fluid and separates the cortex into anatomically defined lobar regions. RESULTS: A significant decrease in cortical gray matter volume was seen for healthy controls in the frontal (2.6%) and parietal (4.1%) regions. For the childhood-onset schizophrenia group, there was a decrease in volume in these regions (10.9% and 8.5%, respectively) as well as a 7% decrease in volume in the temporal gray matter. Thus, the childhood-onset schizophrenia group showed a distinctive disease-specific pattern (multivariate analysis of variance for change X region X diagnosis: F, 3.68; P = .004), with the frontal and temporal regions showing the greatest between-group differences. Changes in white matter volume did not differ significantly between the 2 groups. CONCLUSIONS: Patients with very early-onset schizophrenia had both a 4-fold greater decrease in cortical gray matter volume during adolescence and a disease-specific pattern of change. Etiologic models for these patients' illness, which seem clinically and neurobiologically continuous with later-onset schizophrenia, must take into account both early and late disruptions of brain development.

Adolescent↗
PubMed1999

Clinical and neurobiological correlates of cytogenetic abnormalities in childhood-onset schizophrenia.

OBJECTIVE: Cytogenetic abnormalities are increased in schizophrenia, suggesting a possible etiologic contribution. However, their clinical and pathophysiologic roles in the disorder are unknown. To investigate this, a group of children and adolescents participating in a comprehensive study of childhood-onset schizophrenia were screened for chromosomal abnormalities, and their clinical and neurobiological correlates were examined. METHOD: Cytogenetic screening with the use of high-resolution banding, fluorescent in situ hybridization for chromosome 22q11 deletions, and molecular fragile X testing was undertaken in a group of 47 children and adolescents with very early onset of schizophrenia. Clinical, neurobiological (including brain morphometry), and risk factor measures of the subjects with cytogenetic abnormalities were compared with those of the remaining patients without cytogenetic anomalies. RESULTS: Five patients had previously undiagnosed cytogenetic abnormalities. Lower performance IQ and more pronounced premorbid developmental impairments were seen in this subgroup. Rates of obstetric complications, familial schizophrenia spectrum disorders, and familial eye tracking dysfunction were similar for the patients with and without cytogenetic abnormalities. CONCLUSIONS: Cytogenetic abnormalities appear to be increased in childhood-onset schizophrenia, suggesting an association with a very early age at onset. The data from the subgroup of patients with cytogenetic anomalies are consistent with a model in which a childhood onset of schizophrenia is due to a greater impairment of neurodevelopment secondary to the interaction of a number of factors, particularly genetic ones.

Adolescent↗
PubMed1999

Obstetrical complications and childhood-onset schizophrenia.

OBJECTIVE: Increased obstetrical complications have been reported in individuals with adult-onset schizophrenia, with several studies finding an association between such complications and an earlier age at onset. Consequently, obstetrical records were examined for individuals with childhood-onset schizophrenia to determine if birth complications were more prevalent. METHOD: The birth records of 36 patients with childhood-onset schizophrenia and 35 sibling comparison subjects were rated for birth complications by two psychiatrists who were unaware of group membership. RESULTS: There were no significant differences between the groups in rates of obstetrical complications. Patients with such complications did not have a relatively earlier age at onset of schizophrenia. CONCLUSIONS: A very early age at onset of schizophrenia is probably not due to birth complications.

Age of Onset↗
PubMed1999

A rural population based case-control study of senile cataract in India.

PURPOSE: Senile cataract contributes to 75% of blindness in India and there is a growing backlog of cataract cases needing surgery. The present study seeks clues to the etiology of senile cataract, so that strategies to prevent or even delay cataract formation could be planned. METHODS: Using a community based case-control design, 258 cases & 308 controls from one centre and 301 cases & 591 controls from another were studied. The subjects were from rural areas and were aged 40-60 years. Logistic regression analysis technique was employed to study the associations between senile cataract and various variables. RESULTS: Systolic blood pressure, duration of exposure to sunlight per day were associated with senile cataract in both the centres (OR = 1.4 & 1.5 for systolic BP and 1.6 & 1.4 for exposure to sunlight). Utilization of rice gruel (OR = 0.5), duration of exposure to fire & dust per day (OR = 1.8), family history of cataract (OR = 5.0), use of cheap cooking fuels (OR = 1.8), increased height (OR = 0.7) and increased number of hours of work per day (OR = 0.7) were other variables that showed significant association in either of the centres. CONCLUSION: Senile cataract appears to have a multi factorial etiology. Though the study provided some clues to the etiology of senile cataract, further studies are needed to know the specific role of these factors in the causation of cataract, so that any preventive or control measures could be initiated in the community. Till such time, we have to fall back on the available surgical approach in control of senile cataract.

Adult↗
PubMed1998

Restriction fragment length polymorphism of the L-myc oncogene in non-Hodgkin's lymphoma patients from India.

We examined 89 non-Hodgkin's lymphoma (NHL) patients of Indian origin for EcoRI restriction fragment length polymorphism (RFLP) of the L-myc gene with a view to testing the hypothesis that the presence of the L-myc S-allele predisposes towards NHL. We found no significant difference either in the distribution of the LL, LS and SS genotypes or in the allelic frequencies between the patient group and the control group with the frequencies of L-myc alleles, L (10.0 kb) and S (6.6 kb), being 0.56 and 0.44, respectively, in the patient group and 0.54 and 0.46, respectively, in the control group. However, a higher proportion (70%) of the S-allele was observed in our control group of normal healthy volunteers. Thus, the presence of L-myc S-allele did not indicate increased susceptibility or predisposition to the malignancy.

Adolescent↗
PubMed1998

Brief report: association of sex chromosome anomalies with childhood-onset psychotic disorders.

OBJECTIVE: An apparent excess of sex chromosome aneuploidies (XXY, XXX, and possibly XYY) has been reported in patients with adult-onset schizophrenia and with unspecified psychoses. This study describes the results of cytogenetic screening carried out for pediatric patients meeting DMS-III-R criteria for childhood-onset schizophrenia (COS) and a subgroup of patients with childhood-onset psychotic disorder not otherwise specified, provisionally labeled by the authors as multidimensionally impaired (MDI). METHOD: From August 1990 to July 1997, karyotypes were determined for 66 neuroleptic-nonresponsive pediatric patients (28 MDI, 38 COS), referred to the National Institute of Mental Health for an inpatient treatment trial of clozapine. RESULTS: Four (6.1%) of 66 patients (3 MDI, 1 COS) were found to have sex chromosome anomalies (mosaic 47,XXY; 47,XXY; 47,XYY; mosaic 45,XO, respectively), which is higher than the expected rate of 1 per 426 children or 2.34 per 1,000 in the general population (4/66 versus 1/426, chi 2 = 19.2, df = 1, p = .00001). All cases had been previously undiagnosed. CONCLUSIONS: These findings lend support to a hypothesis that a loss of balance of gene products on the sex chromosomes may predispose affected individuals to susceptibility to additional genetic and environmental insults that result in childhood-onset psychotic disorders. Karyotyping of children with psychotic disorders should be routine.

Adolescent↗
PubMed1998

Functional differentiation along the anterior-posterior axis of the hippocampus in monkeys.

We tested whether the primate hippocampus was functionally heterogenous along its anterior-posterior axis. Two monkeys were trained on both a spatial and nonspatial memory task and the incidence of spatial and nonspatial delay activity in the anterior, middle, and posterior hippocampus was noted. Spatial delay activity (activity in the delay period after the sample stimulus on the spatial memory task) was more common in the posterior than the anterior hippocampus, whereas nonspatial delay activity (activity in the delay period after the sample stimulus on the nonspatial memory task) was evenly distributed throughout the hippocampus. Furthermore, delay neurons in the anterior hippocampus exhibited scalloping delay activity, whereas those in the middle and posterior hippocampus did not. These findings suggest that the hippocampus is functionally heterogeneous and that the posterior regions may be more important for processing spatial information, whereas the anterior regions may be more important for directing or coding movements to points in space.

Acoustic Stimulation↗
PubMed1998

Effect of acute pharmacological reduction of plasma free fatty acids on growth hormone (GH) releasing hormone-induced GH secretion in obese adults with and without hypopituitarism.

In obesity, there is a markedly decreased GH secretion. The diagnosis of GH deficiency (GHD) in adults is based on peak GH responses to stimulation tests. In the severely obese, peak GH levels after pharmacological stimulation are often in the range that is observed in hypopituitary patients. To distinguish obese subjects from GHD patients, it will be necessary to demonstrate that reduced GH responsiveness to a given test is reversible in the former, but not in the latter, group. Recent studies have shown that reduction of plasma free fatty acids (FFA) with acipimox in obese patients restores their somatotrope responsiveness. There are no data evaluating GH responsiveness to acipimox plus GHRH in obese adults with hypopituitarism. The aim of the present study was to evaluate the effect of acute pharmacological reduction of plasma FFA on GHRH-mediated GH secretion in obese normal subjects and obese adults with hypopituitarism. Eight obese patients with a body mass index of 34.2+/-1.2; eight obese adults with hypopituitarism, with a body mass index of 35.5+/-1.9; and six control subjects were studied. All the patients showed an impaired response to an insulin-tolerance test (0.15 U/kg, i.v.), with a peak GH secretion of less than 3 microg/L. Two tests were carried out. On one day, they were given GHRH (100 microg, i.v., 0 min), preceded by placebo; and blood samples were taken every 15 min for 60 min. On the second day, they were given GHRH (100 microg, i.v., 0 min), preceded by acipimox (250 mg, orally, at -270 min and -60 min); and blood samples were taken every 15 min for 60 min. The administration of acipimox induced a FFA reduction during the entire test. Normal control subjects had a mean peak (microg/L) of 23.8+/-4.8 after GHRH-induced GH secretion; previous acipimox administration increased GHRH-induced GH secretion, with a mean peak of 54.7+/-14.5. In obese patients, GHRH-induced GH secretion was markedly reduced, with a mean peak (microg/L) of 3.9+/-1; previous administration of acipimox markedly increased GHRH-mediated GH secretion, with a mean peak of 16.0+/-3.2 (P < 0.05). In obese adults with hypopituitarism, GHRH-induced GH secretion was markedly reduced, with a mean peak (microg/L) of 2+/-0.7; previous acipimox administration did not significantly modify GHRH-mediated GH secretion, with a mean peak of 3.3+/-1.1 (P < 0.05). The GH response of obese patients and obese adults with hypopituitarism was similar after GHRH alone. In contrast, the GH response after GHRH plus acipimox, was markedly decreased in obese adults with hypopituitarism (mean peak, 3.3+/-1.1), compared with obese patients (mean peak, 16.0+/-3.2) (P < 0.05) and control subjects (mean peak, 54.7+/-14.5) (P < 0.01). In conclusion, GH secretion, after GHRH-plus-acipimox administration, is reduced in obese adults with hypopituitarism patients, when compared with obese normal patients. Testing with GHRH plus acipimox is safe and is free from side effects and could be used for the diagnosis of GHD in adults.

Adult↗
PubMed1995

Test-retest reliability of the sensory organization test in noninstitutionalized older adults.

The purpose of this study was to determine the 1-week test-retest reliability of the Sensory Organization Test (SOT), using computer-generated scores and loss of balance (LOB) episodes in noninstitutionalized older adults. The SOT was administered to each subject on two separate days 1 week apart in an out-patient clinic. A volunteer sample of 40 individuals who were at least 65 years of age participated in this study. The main outcome measures were computer-generated scores for the first trial and the average of the three trials in each of the six sensory conditions of the SOT; computer-generated composite score of the six conditions; LOB on the first trial and any of three trials in each condition. The intraclass correlation coefficients (ICC) for the SOT first trial data ranged from .15 in Condition 3 to 0.70 in Condition 5. The ICCs for the SOT average of three trials ranged from 0.26 in Condition 3 to 0.68 and 0.64 in Conditions 5 and 6. Percent agreement was 77% to 100% for LOB on the first trial, as well as LOB on any of three trials of Conditions 1 through 6. As the conditions became more difficult, an increasing number of subjects experienced LOB. Analysis revealed fair to good test-retest reliability for computer-generated scores and good reliability for LOB across some conditions of the SOT. A modification to the current scoring system is suggested which would improve the reliability of the computer-generated scores of the SOT.

Aged↗
PubMed1995

Screening for Barrett's esophagus by balloon cytology.

OBJECTIVE: to determine whether balloon cytology would allow a nonendoscopic diagnosis of Barrett's esophagus. METHODS: In 10 unselected patients with Barrett's esophagus, balloon cytology was performed with a Brandt esophageal cytology balloon catheter prior to endoscopy/esophageal biopsy. Specimens were cytologically evaluated for the presence of goblet cells and/or dysplasia. RESULTS: No patient had goblet cells or definitive columnar cell dysplasia. CONCLUSION: This technique with a commercially available balloon catheter does not allow for a nonendoscopic diagnosis of Barrett's esophagus.

Barrett Esophagus↗
PubMed1993

Sex differences in EEG coherence in normal children.

The idea that sex differences in the execution of different mental tasks mean a different cerebral organization met contradictory results. Sex differences in brain electrical activity were reported by various authors. The EEG coherences show functional and anatomical interrelation, so they may reveal differences in brain organization. This paper tries to demonstrate how sex differences are manifested in EEG coherences, in 42 right-handed control children, 18 girls and 24 boys, aged 7.6 to 13.3. Since the effect of age is high on EEG measurements, regression against age was calculated and eliminated. The Z-transformed coherence values were compared by Student's t-test. The results obtained showed that girls had higher right intrahemispheric coherence values than boys in all bands. These sex differences were more numerous in the theta band. The interhemispheric differences were slight and girls had higher coherences in all bands except for the alpha band, where boys had higher interhemispheric coherence than girls. These results show slight but consistent differences in the functional organization of the right hemisphere by sex and reveal the necessity to elaborate separated EEG norms for boys and girls.

Adolescent↗