The reliability and validity of general psychotic rating scales with people with mild and moderate intellectual disabilities: an empirical investigation.

BACKGROUND: Whilst assessment tools have been developed to diagnose schizophrenia in people with mild intellectual disabilities (IDs), little attention has been paid to developing reliable and valid dimensional measures of psychotic experiences with this population. This study investigates the reliability and validity of two such measures developed for the general adult psychiatric population, the Positive and Negative Syndrome Scale (PANSS) and the Psychotic Symptom Rating Scales (PSYRATS), with a population of adults with mild IDs. METHOD: Sixty-two adults with mild IDs were interviewed using the PANSS and PSYRATS, and independently interviewed using the Psychiatric Assessment Schedule--Adults with Developmental Disability (PAS-ADD) to obtain psychiatric diagnoses to the criteria of the International Classification of Diseases--Tenth Revision (ICD-10). On the basis of ICD-10 diagnosis, participants were divided into three groups: psychosis (n=11); other mental health problem (n=14); no mental health problem (n=37). PANSS and PSYRATS subscale scores were compared across these three groups and were correlated with PAS-ADD symptom scores across a number of PAS-ADD symptom domains. RESULTS: All PANSS and PSYRATS subscales showed adequate internal reliability, largely good test-retest reliability, and logical inter-correlations between subscales. The PANSS positive symptoms and the PSYRATS auditory hallucinations subscales differentiated between the psychosis group and the other groups; the PANSS general symptoms subscale differentiated between the psychosis and no mental health problem groups; and the PANSS negative symptoms and the PSYRATS delusions subscales did not differentiate between the three groups. CONCLUSIONS: The PANSS and PSYRATS are promising measures for use with people with mild IDs and psychotic experiences, although further investigation of items relating to negative symptoms and delusions is warranted.

Phenylketonuria in adulthood: a collaborative study.

During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjects who had completed the original study (1967-1983), and was asked to evaluate as many as possible using a uniform protocol and data collection forms. In a subset of cases, magnetic resonance imaging and spectroscopy (MRI/MRS) were performed to study brain Phe concentrations. The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers, who had an increased rate of eczema, asthma, mental disorders, headache, hyperactivity and hypoactivity. Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations. Abnormal MRI results were associated with higher brain Phe concentrations. Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural problems.

Quantitative amino acid analysis using a Beckman system gold HPLC 126AA analyzer.

BACKGROUND: The Beckman 6300/7300 analyzer, which was widely used for amino acid (AA) analysis, is no longer commercially available. METHODS: To set up an affordable AA analysis program, a Beckman system gold HPLC 126AA analyzer and Pickering Laboratories reagents were used. Two quantitative AA analysis programs were developed. One was an 18-min short program quantitating seven AAs from plasma and dried blood spots (DBS) specimens using Lithium eluents Li-365 and Li-375 at 70 degrees C column temperature. The short program could be used for diagnosis and follow-up dietary management for phenylketonuria (PKU), maple syrup urine disease (MSUD), tyrosinemia and homocystinuria patients. The second program was a 118-min long AA screening panel quantitating 40 AAs using Lithium eluents Li-275, Li-365 and Li-375 at 32, 48 and 72 degrees C column temperatures from plasma and urine specimens. RESULTS: The values obtained from DBS specimens were in good agreement with certified results from the Centers for Disease Control and Prevention. The values obtained from plasma and urine samples were in good correlation with those obtained from Beckman 6300 analyzer (0.9076 < or = r < or = 0.999). CONCLUSIONS: Amino acid quantitation from physiological samples using a Beckman 126AA Analyzer and Pickering Laboratories reagents was useful for clinical diagnosis and monitoring of aminoacidopathies.

Malonyl CoA decarboxylase deficiency: C to T transition in intron 2 of the MCD gene.

Malonyl CoA decarboxylase (MCD) is an enzyme involved in the metabolism of fatty acids synthesis. Based on reports of MCD deficiency, this enzyme is particular important in muscle and brain metabolism. Mutations in the MCD gene result in a deficiency of MCD activity, that lead to psychomotor retardation, cardiomyopathy and neonatal death. To date however, only a few patients have been reported with defects in MCD. We report here studies of a patient with MCD deficiency, who presented with hypotonia, cardiomyopathy and psychomotor retardation. DNA sequencing of MCD revealed a homozygous intronic mutation, specifically a -5 C to T transition near the acceptor site for exon 3. RT-PCR amplification of exons 2 and 3 revealed that although mRNA from a normal control sample yielded one major DNA band, the mutant mRNA sample resulted in two distinct DNA fragments. Sequencing of the patient's two RT-PCR products revealed that the larger molecular weight fragments contained exons 2 and 3 as well as the intervening intronic sequence. The smaller size band from the patient contained the properly spliced exons, similar to the normal control. Western blotting analysis of the expressed protein showed only a faint band in the patient sample in contrast to a robust band in the control. In addition, the enzyme activity of the mutant protein was lower than that of the control protein. The data indicate that homozygous mutation in intron 2 disrupt normal splicing of the gene, leading to lower expression of the MCD protein and MCD deficiency.

Familial deletion of chromosome 18 (p11.2).

Familial transmission of del (18p) syndrome from a mother to her daughter is rare and has been reported only once before. We report a female patient referred to us at age 18 years because of mental retardation associated with short stature. Similar clinical features are also seen in her mother. Chromosome analysis revealed a 46,XX, del (18) (p11.2) karyotype in both the proposita and her mother. Fluorescence in situ hybridization with whole chromosome paint for chromosome 18 showed no evidence of translocation. Because of the familial transmission of del (18p), this case has wider implications in genetic counseling.

Partial trisomy 13q identified by sequential fluorescence in situ hybridization.

We report on a 19-month-old boy with partial trisomy 13q resulting from a probable balanced translocation involving chromosomes 1 and 13. The infant presented with omphalocele, malrotation, microcephaly with overriding skull bones, micrognathia, apparently low-set ears, rocker-bottom feet, and congenital heart disease, findings suggestive of trisomy 13. Karyotypic studies from peripheral blood lymphocytes documented an unbalanced karyotype 46,XY,-1,+der(1). The mother's chromosomes were normal, and the father was not available. Conventional cytogenetic techniques were unable to identify the extra material on the terminal 1q. Using fluorescence in situ hybridization (FISH) on the GTL-banded metaphases, the extra material on 1q was identified as the terminal long arm of 13, thus resulting in partial trisomy 13 (q32-qter).

Reversal of neuromuscular blockade in humans by neostigmine and edrophonium: a mathematical model.

Generalizations of the integrated model describing the interaction of nondepolarizing neuromuscular blocking drugs with reversible anticholinesterase drugs described in Unadkat et al. (1) are reported. The models can deal with possible incomplete reversal (irreversible block) and/or noninstantaneous anticholinesterase kinetics. Experimental data were obtained from 22 human volunteers. Different levels of steady-state vecuronium block were induced in each volunteer (in the range of 50% to 95%), and reversed by short infusions of edrophonium (10 volunteers) or neostigmine (12 volunteers). Edrophonium or neostigmine concentrations and twitch tension (measured as the force of thumb adduction) were measured. The generalized integrated models fit the data well. In the case of neostigmine we find a nondistributional delay in its action. We relate this delay to the slow decarbamylation rate of the (neostigmine-induced) carbamylated anticholinesterase observed in vitro, and are able to model such noninstantaneous anticholinesterase kinetic processes. For both edrophonium and neostigmine we detect an inverse relationship between the (induced) level of initial block and maximal percentage recovery.

Intellectual development in 12-year-old children treated for phenylketonuria.

Intelligence and achievement test scores were evaluated for 95 12-year-old children with phenylketonuria who had begun dietary therapy during the neonatal period. Dietary control of blood phenylalanine below 900 mumol/L was maintained beyond age 10 years in 23 children; 72 others had blood phenylalanine persistently above that level at ages ranging from 18 months to 10 years. Test scores at age 12 years were negatively correlated with the age at initiation of diet and with blood phenylalanine levels from ages 4 to 10 years, and positively correlated with parent IQ scores and the age at loss of dietary control. Children who maintained phenylalanine levels below 900 mumol/L beyond age 10 years showed no deficits in test scores, except for arithmetic, the scores of which declined between ages 6 and 12 years in 90% of the children in this study. These data strongly support a recommendation that dietary restriction of phenylalanine should be maintained through adolescence.

A comparison of male admissions to a special hospital 1970-71 and 1987-88.

Characteristics of 109 male patients admitted over a two-year period to a Special Hospital are described and discussed. Comparison is made with the results from a previous study conducted in another Special Hospital (Broadmoor) some fifteen years ago. Admissions still originate mainly from the courts, the penal system, and the NHS. However, the pattern of admissions has changed, influenced in part by the advent of the Regional Secure Unit programme, and the 1983 revision of the Mental Health Act. Very few admissions were diagnosed as suffering from a primary affective disorder. Patients suffering from psychopathic disorder had committed few crimes of murder and manslaughter. Possible reasons for these and other findings are discussed. It is concluded that the Special Hospitals continue to play a distinct and essential role.

Violent incidents on special care wards in a special hospital.

Records of 116 violent incidents perpetrated by special care patients over a twelve-month period were retrospectively examined. There was a marked seasonal variation in the number of incidents. Incidents took place predominantly in the seclusion rooms and in communal areas having relatively high patient density. Patients admitted from the National Health Service following unmanageable violent behaviour were over-represented. A small number of patients were responsible for a high proportion of incidents. Implications for prevention are discussed.

New multiple congenital anomalies/mental retardation syndrome with cardio-facio-cutaneous involvement--the CFC syndrome.

Eight patients (4 males, 4 females) were affected with a previously undefined multiple congenital anomalies/mental retardation syndrome which was designated the Cardio-Facio-Cutaneous (CFC) syndrome and which includes congenital heart defects, characteristic facial appearance, ectodermal abnormalities, and growth failure. Cardiac defects were variable, the most common being pulmonic stenosis and atrial septal defect. Typical facial characteristics were high forehead with bitemporal constriction, hypoplasia of supraorbital ridges, antimongoloid slant of palpebral fissures, depressed bridge of nose, and posteriorly angulated ears with prominent helices. The hair was usually sparse and friable. Skin changes varied from patchy hyperkeratosis to a severe generalized ichthyosis-like condition. All cases were sporadic in occurrence, there was no family history of consanguinity, and chromosomes were normal. Although presumed to be genetic, the cause of the CFC syndrome remains unknown.

Newborn hypothyroid screening. The private sector.

Newborn hypothyroid screening in four private hospitals was prospectively evaluated and compared with a state screening program. During 1982 the hospitals screened a total of 10,786 infants compared with 47,525 by the state. Eight cases of primary hypothyroidism were confirmed by the state, for an incidence of one in 5,941. No cases were detected by the hospital programs. The cost for all infants screened in the private hospitals was 51.5 times more than the total cost of the state program, yet the state screened 4.4 times more infants.

Patients in a clinic for children with multiple handicaps: a retrospective diagnostic evaluation.

This study illustrates the effectiveness of an outpatient facility in evaluating patients with a variety of handicapping disorders. A multidisciplinary approach, such as the one used in the Child Study Clinic, is the most effective and most efficient mode of evaluating handicapped children, though hospitalization is occasionally required to further evaluate such complicated problems. Every child with mental retardation, birth defects, or multiple handicaps requires a thorough evaluation for the purposes of diagnosis, treatment, and the prescription of long-term educational and occupational goals. Family history often indicates the need for genetic counseling.

Familial gynecomastia without hypogonadism.

A family, six members of which had gynecomastia without hypogonadism, is presented. Endocrine studies failed to show the specific nature of breast enlargement in the patients. Chromosomal studies using peripheral leukocytes resulted in normal findings. In one of the patients, chromosomal studies were done using breast tissue and fascia, and again no abnormalities could be detected. The mode of inheritance may be autosoma dominant with sex limitations; however, X-linked inheritance cannot be ruled out.

Chromosome variants in children with psychiatric disorders.

The authors studied the frequency of chromosome variants in 48 hospitalized children with psychiatric diagnoses (study group) in comparison with 10 hospitalized children with nonpsychiatric diagnoses (control group) and the results of three surveys of newborn children. They found that the frequency of variants in their study group was elevated in comparison with their control group and with the newborn surveys.