Biomedical subjects
Publications and source records attributed to N Brand.
A Sephardi Jewish family is reported in which the two brothers had mental retardation, lower limb spasticity and bilateral clasped thumbs anomaly. This X-linked recessive disorder has only been reported twice. We believe this syndrome comprises a distinct entity among the X-linked mental retardation syndromes.
The present report describes a benign disorder of neonates or young infants presenting with generalized hypertonicity accompanied by brisk muscle stretch reflexes, intermittent clonus, and exaggerated startle response. This condition is termed hyperexplexia, and may be either familial or sporadic. Two affected families are reported: Two sisters and their mother are involved in the first family; in the second family, where the parents are asymptomatic first degree cousins, all three siblings suffer from hyperexplexia of various severity. Nose tapping in infants of affected families induced a uniform reaction of facial twitching accompanied by head extension, and a generalized flexor spasm, all of which may be a hallmark of hyperexplexia. Severely hypertonic infants were treated with small doses of benzodiazepines and improved markedly, all becoming asymptomatic by two years of age. Unnecessary investigation and treatment may be avoided by sufficient awareness of possible hyperexplexia.
High-dose intravenous immunoglobulin was effective in 3 children with severe Guillain-Barre syndrome (GBS). They presented with mild to moderate, flaccid weakness which progressively deteriorated to severe tetraparesis and weakness of ocular, facial and bulbar muscles. 1 of them was treated with steroids with no response. Serum immune globulins were infused (1g/kg/day) for 2 consecutive days. There was marked clinical improvement in all 3 after the second day of infusion, and there were no adverse affects. All became ambulatory and were able to walk within the first week. Ocular, facial and bulbar impairment gradually subsided and disappeared, as did hypertension in 1. A 6-year-old boy completely recovered after 3 weeks while the 2 girls, both aged 9 years, still have mild weakness which is gradually improving. High-dose immunoglobulin therapy may be effective in children with severe GBS, with no significant adverse effects. It presumably provides idiotypic antibodies that block the autoimmune process responsible for demyelination.
We report on 6 patients with short stature and progressive enchondromatous-like changes of the vertebral bodies and the metaphyses of the long bones. Parental consanguinity was observed in 5 of 6 cases, supporting autosomal recessive inheritance. In spite of the similarity in radiographic changes and body proportions, genetic heterogeneity is suggested by the presence of CNS calcifications in 3 patients. Two of the latter had progressive quadriparesis. We tentatively classified these patients into 2 provisional types. An iliac crest biopsy in one of the patients with "type I" disease did not demonstrate enchondromatosis. Light and transmission electron microscopic studies demonstrated large cisterns and small inclusion bodies containing a flocculent material within the rough endoplasmic reticulum of the chondrocytes. Based on the histological and radiographic findings, we propose to classify these conditions among the spondylometaphyseal skeletal dysplasias.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Two cDNAs encoding two human receptors for retinoic acid (RA), RAR-alpha and RAR-beta, have been characterized recently. Synthetic peptides corresponding to the cDNA-deduced amino acid sequences unique to RAR-alpha and RAR-beta were used to generate anti-RAR-alpha antiserum (SP171) and anti-RAR-beta antisera (SP172 and SP248). The specificity of these antisera was confirmed both by immunocytochemical detection of these receptors in COS-1 cells transfected with RAR-alpha and RAR-beta expression vectors and by immunoblot analyses performed with whole extracts of these cells. We also demonstrate that these antisera recognize RAR-alpha and RAR-beta endogenously expressed in the RA-responsive human promyelocytic leukemia cell line HL-60.
We have previously described a human complementary DNA that encodes a novel protein which is homologous to members of the steroid/thyroid nuclear receptor multigene family. This novel protein (hap for hepatoma) exhibits strong homology with the human retinoic acid receptor (RAR) which has been recently characterized. To test the possibility that the hap protein might also be a retinoid receptor, a chimaeric receptor was created by replacing the putative DNA binding domain of hap with that of the human oestrogen receptor (ER). The resulting hap-ER chimaera was then tested for its ability to trans-activate an oestrogen-responsive reporter gene (vit-tk-CAT) in the presence of possible receptor ligands. Here we show that retinoic acid (RA) at physiological concentrations is effective in inducing the expression of this reporter gene by the hap-ER chimaeric receptor. This demonstrates the existence of two human retinoic acid receptors designated RAR-alpha and RAR-beta.
Recombinant plasmid containing cDNA insert from the human retinoic acid receptor was radiolabeled and hybridized in situ to metaphase chromosome preparations. The results localized the human retinoic acid receptor to the q21 band of chromosome 17.
Carnitine deficiency occurring in families has been rarely reported and the genetic transmission has not yet been clearly elucidated. Five members of one family showing marked heterogeneity of carnitine deficiency states are presented. In three patients, there was no correlation between measurable carnitine levels in serum and muscle and the clinical findings. The parents, who are remote relatives from an isolated village in Kurdistan (Iraq), had low muscle carnitine levels; however, they were asymptomatic. One son, with systemic carnitine deficiency causing muscle weakness and recurrent episodes of severe hepatic encephalopathy, died at 3 years of age. His brother had mild proximal muscle weakness associated with low muscle carnitine levels. He was successfully treated with L-carnitine and prednisone. A daughter is asymptomatic, but with low serum and muscle levels of carnitine. The marked heterogeneity of carnitine deficiency states within one family, where both parents had low muscle carnitine levels, suggests an autosomal recessive inheritance with variable expression.
The memory scanning performance of both unipolar and bipolar depressives and patients with anxiety states was compared with that of control subjects. Four versions of Sternberg's memory comparison task were used. Unipolar depressives showed impaired memory scanning in 3 of the tasks compared with controls, and in one task compared with patients with anxiety states. They were also slower than the other patients and controls in the non-scanning processing stages. They seemed to adopt a less efficient search strategy, and showed more controlled processing as opposed to automatic detection in a paper-and-pencil version of the task.
Twenty-two patients with inherited hyperammonemic syndromes are presented. These patients represent 22 different families. The diagnosis was based mainly on family history, blood ammonium levels, acid base balance, urinary orotic acid, urinary and plasma amino acids and organic acids. The final diagnosis was confirmed by determination of liver enzyme activity. In 12 patients (54%), the first clinical manifestations were noticed after the neonatal period; 7 patients (31%) were diagnosed after infancy, and 8 (23%) after the age of 8 years. Two patients who represent the late-onset group of inherited hyperammonemic syndromes are presented in detail. The three most common diagnoses were ornithine transcarbamoylase deficiency, carbamoyl phosphate synthetase deficiency, and lysinuric protein intolerance, which comprised 59% of the diagnosed patients. Our data, based on one of the largest series reported, reveal a relatively large percentage of late-onset inherited hyperammonemic syndromes as compared with previous reports.
Mode of presentation (visual or auditory) of a multitrial free recall test is stressed as an important factor in improving the diagnosis of certain neurological patients. For further use in neuropsychological research, an experiment was carried out using normal subjects, in which the effects of presentation mode and order of modality were investigated. There were no differential effects of these variables on several parameters, such as the number of words recalled and the learning curve. The time needed for the responses in immediate recall was the same in both auditory and visual conditions. In delayed recall, however, the interresponse times were significantly shorter when words had been presented auditorily than when presented visually. The results are discussed in light of further application in the field of neuropsychology.
In an 18-month-old girl affected by mucolipidosis IV (ML IV) with mild corneal clouding, normal retinal activity was documented by electroretinogram (ERG) and slightly delayed optic pathway conduction was revealed by visual evoked potential (VEP). Re-examination 9 years later disclosed severe retinal alterations resulting in atrophy with reduced photopic and missing scotopic ERG components and flat VEP. These fundoscopic and electrophysiologic deteriorations in ML IV suggest progressive rod-cone impairment similar to tapetoretinal dystrophy.
In spite of the fact that therapeutic and toxic ranges of phenytoin are well defined, it is still often difficult to calculate an optimal dosage regimen because of the nonlinear saturable kinetics of the drug. Predictions are much more complicated when impaired bioavailability exists. We estimated individual Michaelis-Menten pharmacokinetic parameters from two reliable steady-state serum concentrations of phenytoin following two different drug dosages in 13 epileptic children treated with a preparation that has been shown to be poorly absorbed. Their calculated average Vmax (the maximal rate of elimination) was significantly higher than the average for their age (12.21 and 9.28 mg/kg/day, respectively) (p less than 0.05). The impaired bioavailability did not affect the values of Km. In the six children who needed a third adjustment of dosage, the observed steady-state serum levels of phenytoin with dosage regimens calculated from the individual pharmacokinetic parameters agreed well with the predicted levels (r = 0.97, p less than 0.01). Our data suggest that Michaelis-Menten kinetics can be used to predict phenytoin levels even when impaired bioavailability exists, providing that the fraction of absorption is constant.
Single-dose intravenous phenytoin (9.4-21.3 mg/kg) effectively eradicated seizures within 3 minutes in 12 out of 13 patients in status epilepticus. Eleven additional patients were treated prophylactically. No adverse effects were observed and neurological status was unaltered in all 24 cases. Phenytoin volume of distribution was found to decline significantly with age from 1.6 L/kg at 1 year to 0.6 at 10 years (P less than 0.01). Estimates of Vmax, the maximal rate of phenytoin metabolism, were obtainable in 8/24 patients and were in the expected range (10.6 +/- 4.2 mg/kg/day) for their age (6.6 +/- 2.8 years). Therapeutic serum concentrations (initial post distribution values 17.9 +/- 9.0 micrograms/ml) were maintained for more than 10 hours in 15/24 patients. Single-dose intravenous phenytoin is both effective and safe in the treatment and prevention of epileptic seizures in pediatric patients.
Explore the source record for details and available documents.
In unilateral Visual Half-Field tasks visuospatial and linguistic processing were compared. In a Word Matching task subjects judged the physical identity of simultaneously presented pairs of three-letter words or legal nonwords. No mainfield effects were found, but word pairs were recognized better and faster as "same" than nonword pairs. Latencies and errors in "different" pairs increased monotonically with position of letter change in the left but not in the right visual field (RVF), suggesting a serial, letter-by-letter way of processing for the right hemisphere and a whole word approach for the left. At this perceptual level the ability to store lexical information from the icon is stressed as a hemisphere-specific factor. In a Lexical Decision task the same subjects judged the same items on the word/nonword dimension. A RVF advantage associated with words as compared to nonwords occurred, as expected. Additional analysis suggests that order and difficulty of tasks may influence females' laterality, as compared to that of males.