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Biomedical subjects

D Friedman

Publications and source records attributed to D Friedman.

At least 19 recordsLinked to original sources
PubMed1995

Event-related potential and behavioral correlates of semantic processing in Alzheimer's patients and normal controls.

In normal young adults, N400 amplitude varies inversely with the extent to which a word has been primed by its preceding semantic context. Based on a series of behavioral studies, it appears that in Probable Alzheimer's patients (PAD) the organization of semantic memory is disrupted such that specific items within a category lose their distinction, although superordinate information remains relatively intact. The present study examined whether the N400 gradient which has been found with normal young adults would also reflect this loss of discriminability among semantically related items in PAD patients. Ten normal young adults, 10 normal elderly, and 6 "mild" PAD patients made speeded (but accurate) sense/nonsense decisions to the terminal words of a series of highly constrained sentence contexts. The terminal words belonged to one of four stimulus types which varied as a function of relatedness to a highly expected word. Counter to our predictions, N400 amplitude was identically responsive to semantic relatedness in the young normal and PAD groups, but was characterized differently in the normal elderly. Given the significantly greater number of errors committed by PAD patients, we concluded that their disruption in semantic processing occurs at some point between the elicitation of N400 and the generation of the reaction time response. The anomalous N400 pattern in the normal elderly appeared to be strategy related and superimposed upon an otherwise normal semantic network.

Adult↗
PubMed1995

The development of selective attention as reflected by event-related brain potentials.

The development of auditory selective attention was assessed using event-related brain potentials (ERPs) and behavioral measures, with children (mean age = 8.1), adolescents (14.4), and young adults (23.8) as subjects. During separate blocks, subjects heard two sequences of pure tones (low- and high-pitched) or consonant-vowels (CVs; for example, ba vs da). Subjects were required to attend to one of the two stimuli in order to detect a deviant target embedded within the attended sequence, while ignoring the sequence comprised of the other stimulus (which also contained standard and deviant stimuli). The frequent standards were always 100 ms in duration, whereas the infrequent targets were of longer duration. The effect of selective attention was operationalized by computing the Nd difference waveform (ERP elicited by the unattended standard subtracted from that elicited by the attended standard). There was an increase in early Nd amplitude (measured from about 200 to 400 ms) and a decrease in its latency for both pure tones and CVs from childhood through young adulthood. For the amplitude measure, this effect was much more marked for CVs. Additional analyses indicated that the major effect of age involved reduction of negative-going ERP amplitude elicited by stimuli in the unattended channel, suggesting that with age there is an improvement in the narrowing of the attentional focus, with the major change taking the form of greater facility in rejecting stimuli in the unattended channel. Age-related shifts in scalp distribution of both early and late Nd were seen as consistent with, respectively, age-related changes in the way attention was allocated to the two input channels, and in the way in which the attentional trace was maintained by selective rehearsal.

Adolescent↗
PubMed1995

Children who are shot: a 30-year experience.

Three data sets describe the pattern of gunshot injuries to children from 1960 to 1993: The Harlem Hospital pediatric trauma registry (HHPTR), the northern Manhattan injury surveillance system (NMISS) a population-based study, and the National Pediatric Trauma Registry (NPTR). A small case-control study compares the characteristics of injured children with a control group. Before 1970 gunshot injuries to Harlem children were rare. In 1971 an initial rise in pediatric gunshot admissions occurred, and by 1988 pediatric gunshot injuries at Harlem Hospital had peaked at 33. Population-based data through NMISS showed that the gunshot rate for Central Harlem children 10 to 16 years of age rose from 64.6 per 100,000 in 1986 to 267.6 per 100,000 in 1987, a 400% increase. The case fatality for children admitted to Harlem Hospital (1960 to 1993) was 3%, usually because of brain injury, but the majority of deaths occurred before hospitalization. During the same period, felony drug arrests in Harlem increased by 163%. The neighboring South Bronx experienced the same increase in gunshot wound admissions and felony arrests from 1986 to 1993. The NPTR showed a similar injury pattern for other communities in the United States. In a case-control analysis. Harlem adolescents who had sustained gunshot wounds were more likely to have dropped out of school, to have lived in a household without a biological parent, to have experienced parental death, and to have known of a relative or friend who had been shot than community adolescents treated for other medical or surgical problems.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Primary omental torsion in children.

Primary torsion of the omentum is an unusual cause of an acute abdomen and commonly mimics acute appendicitis. The following report of four obese children is supportive of obesity as a predisposing factor. The paucity of gastrointestinal symptoms, anorexia, nausea, vomiting, and the relatively long duration of symptoms, may increase the index of suspicion. In the majority of cases, the diagnosis is made intraoperatively by digital exploration through the muscle-splitting incision. The torsed omentum is easily delivered through the same incision, and excision results in complete recovery.

Adolescent↗
PubMed1995

Pupillary and visual thresholds in young children as an index of population vitamin A status.

A prototype scotopic sensitivity machine was used to evaluate pupillary and visual thresholds for 295 Indonesian children aged 1-5 y, most of whom were initially vitamin A-deficient. Subjects were tested 6 and 9 mo after receiving a high dose of vitamin A. A group of 136 older children was tested at 6 mo after dosing; all subjects underwent testing at 9 mo. After testing at 9 mo, children randomly received either a second high dose of vitamin A or placebo and were tested a final time 2 wk later. Children with abnormal pupillary thresholds had significantly higher relative dose responses (RDRs) (P < 0.01) and significantly lower serum retinol values (P = 0.05) than did normal children. The mean pupillary threshold rose (eg, retinal sensitivity fell) as vitamin A status deteriorated between 6 and 9 mo after initial dosing, and was significantly different from a group of normal American children tested previously (P < 0.001). After placebo-controlled dosing, the decline in pupillary and visual thresholds (rise in retinal sensitivity) was significant for children receiving vitamin A but not for children receiving placebo.

Aging↗
PubMed1995

Vertebral artery injury after acute cervical spine trauma: rate of occurrence as detected by MR angiography and assessment of clinical consequences.

OBJECTIVE: The purposes of this study were to assess prospectively the frequency of vertebral artery injuries after major acute cervical spine trauma as determined by MR angiography and to assess the clinical consequences of these injuries. SUBJECTS AND METHODS: During a 6-month period, 37 patients who had major acute nonpenetrating cervical spine trauma were examined with MR imaging, usually within 24 hr of the injury. Routine spin-echo and gradient-echo images were supplemented by two-dimensional time-of-flight MR angiography of the extracranial head and neck vessels. The vertebral arteries were independently assessed by two neuroradiologists for nonvisualization, focal narrowing, or focal widening. Two patients had conventional angiographic correlation. The medical records of these 37 patients were also reviewed to determine the type of spinal injury, neurologic deficit on admission, and evidence of an intracranial neurologic deficit due to vertebral artery injury. The MR angiograms of 37 control subjects were interpreted to help determine the specificity of MR angiography; those studies were assessed only for the presence or absence of the vertebral arteries. RESULTS: Findings on MR angiograms were abnormal in nine patients (24%). In seven cases, one vertebral artery was diagnosed as nonvisualized (occluded) or focally narrowed; one patient had bilateral vertebral artery injuries; and one patient had nonvisualization of the left common carotid and left vertebral arteries. In all 37 control subjects, both vertebral arteries were identified on MR angiograms. A significant difference in the frequency of vertebral artery nonvisualization (occlusion) was found between the trauma and control populations. The patient with bilateral vertebral artery injuries died 2 days after hospital admission of a massive infarction of the right cerebellar hemisphere. The other eight patients with vertebral artery injuries, and the remaining 28 patients with normal findings on MR angiograms, had no intracranial neurologic deficits that could be ascribed to a major arterial injury. CONCLUSION: In our experience, vertebral artery injuries due to major cervical spine trauma as determined by MR angiography are common. Although these vascular abnormalities usually remain clinically occult, a small percentage of patients may suffer devastating neurologic complications of posterior fossa infarction. Noninvasive assessment of the vertebral arteries by means of MR imaging should be an integral part of the evaluation of the acutely injured cervical spine.

Acute Disease↗
PubMed1994

Determination of the catalytic site of creatine kinase by site-directed mutagenesis.

Site-directed mutagenesis was used to alter the amino-acid residues at the presumed catalytic site Cys-283 and ATP binding site Asp-340 of human creatine kinase B cDNA. In addition, a highly conserved arginine residue, Arg-292, was also mutated. Transfection of 0.1 to 1 microgram of recombinant plasmid into COS cells produced increasing creatine kinase activity in the cell lysate. The expression of mutant Cys283-Tyr and Cys283-Ser resulted in complete abolition of homodimer BB isoform enzymatic activity without alteration of the capacity for dimerization. Expression of mutants Arg292-His, Arg292-Leu, and Arg292-Gln produced non-functional homodimers, whereas expression of mutant Arg292-Lys produced a homodimer with enzymatic activity that was 42% of the enzymatic activity of the wild type. Expression of the Asp340-Glu mutant creatine kinase did not alter enzyme activity as compared to the wild type. Following heterodimerization, there was inhibition of the normal subunit by the mutant subunit, for both the BB and the MB dimer. The results showed residues Cys-283 and Arg-292 are essential for enzyme catalysis. The best fit model for the dimer is one in which there is close apposition of the two catalytic sites. The interaction of the individual subunits during dimerization provides a molecular approach for dominant negative modulation of the creatine kinase isozyme system in future genetic manipulative experiments.

Base Sequence↗
PubMed1994

Atrial natriuretic peptide response to postural change and medication in familial dysautonomia.

Circulating atrial natriuretic peptide (ANP) was assayed before and after postural change and exercise in 54 patients with familial dysautonomia (FD) and 20 controls. ANP levels were compared with blood pressure, heart rate, plasma catecholamines and parameters of renal function. Compared with controls supine FD subjects had elevated blood pressures, heart rates and ANP levels (39 +/- 4 pg/ml vs. 23 +/- 3 pg/ml, p < 0.01). With the erect posture and exercise in FD subjects, blood pressure fell below control values, with ANP lowered. In FD subjects, blood pressure was correlated with ANP levels when supine and when erect and with heart rate post exercise. In controls, ANP levels did not correlate with other parameters. In FD patients on metoclopramide, supine and erect blood pressure and ANP levels were higher. FD subjects treated with fludrocortisone, had elevated supine and erect noradrenaline (p < 0.05 and p = 0.06); and those on diazepam had lower erect and post exercise noradrenaline (p < 0.05), but ANP levels were similar. In conclusion, sympathetic denervation may increase FD patients' responsiveness to other regulators of cardiovascular integrity, such as ANP. In addition, circulating ANP and catecholamines in FD subjects appear to be influenced by commonly used medications, such as metoclopramide.

Adolescent↗
PubMed1994

ERP amplitude and scalp distribution to target and novel events: effects of temporal order in young, middle-aged and older adults.

Event-related brain potentials (ERPs) were recorded from young (mean age = 24.1), middle-aged (48.7) and older (69.7) adults during a version of the oddball paradigm, in which 48 unique, unexpected novel stimuli were interspersed with equally rare instructed targets. As older relative to younger adults are thought to differ in their ability to inhibit the processing of task irrelevant information, we expected, based on previous work, that novel stimuli would retain their 'novelty' longer in older than in younger adults. To assess this, P3 amplitude and scalp topography elicited by novels and targets were analyzed as a function of stimulus number (n = 6) within the block and as a function of block number (n = 4). The results were in line with the prediction: While the younger adults' P3 scalp distribution shifted from a relatively more frontal to a relatively more posterior focus as a function of novel number within the block, this was not evident in the scalp topographies of the older adults. Coupled with the older adults' elevated false alarm rates to novel stimuli, the data are consistent with a change in frontal lobe function with increases in age.

Adult↗
PubMed1994

Implicit retrieval processes in cued recall: implications for aging effects in memory.

Aging produces deficits in what has come to be called explicit or direct memory, in which subjects must consciously retrieve information from long-term memory. In contrast, many studies have shown that when implicit or indirect memory is tested, old and young subjects perform equivalently. The present study manipulated orienting instructions (structural vs. semantic) for indirect (stem completion) and direct (cued recall) memory tasks for both young and old subjects. Contrary to previous research, older subjects produced equivalent performance to young subjects on the direct test as well as on the indirect test, and performance of both groups was worse in the direct than indirect test. In addition, semantic orienting activity at study led to greater learning on the indirect test than structural orienting for both groups, although the levels of processing effect was greater for the direct test. We attribute the unexpected lack of age difference on the direct test to its difficulty, which led subjects to adopt an implicit (generate + recognize) rather than an explicit retrieval strategy during the cued recall task. Because the elderly are not impaired with regard to either implicit retrieval or recognition, this strategy produced equivalent performance in the two groups.

Adult↗
PubMed1994

Event-related potentials (ERPs) as indicators of risk for schizophrenia.

Evidence is reviewed concerning the viability of cognitive event-related potential (ERP) indices to serve as psychophysiological markers for liability to schizophrenia and schizophrenia-related disorders. Methodologic problems that hinder the establishment of ERPs as such markers are also detailed. The ERP data from prospective high-risk and family-transmission paradigms were subjected to criteria that have been used to establish the marker status of a psychobiological variable. It is concluded that (1) there is a clear need for more studies of ERP component stability and of transmission of ERP parameters within normal families; (2) multiple tasks (in addition to the oddball experiment) must be used to probe the range of information-processing deficits in the schizophrenic syndrome; (3) investigators should pay greater attention to the scalp distribution of ERP components; and (4) profiles of multiple ERP indices may be required to enhance the probability of achieving diagnostic specificity.

Arousal↗
PubMed1994

Brain event-related potential correlates of overfocused attention in obsessive-compulsive disorder.

A hypothesis of overfocused attention in obsessive-compulsive disorder was investigated by measuring auditory event-related potentials (ERPs) during a selective attention task. Unmedicated patients (n = 18) with this disorder showed significantly larger attention-related processing negativity (PN), with earlier onset and longer duration, than did normal controls (n = 15). In the N200 region (160-250 ms), PN was larger in patients with fewer nonspecific neurological soft signs. This task, however, did not yield any group differences in mismatch negativity (N2a) or classical N200 (N2b). P300 amplitudes for attended targets were smaller for patient than normal groups, but the reverse was true for P300 and positive slow wave amplitudes for unattended nontargets. Collectively, these ERP abnormalities suggest a misallocation of cognitive resources. Because of the importance of the frontal lobe in the control of selective attention, PN enhancement in patients with obsessive-compulsive disorder may reflect hyperactivation of this region. This conceptualization is consistent with recent functional neuroimaging findings.

Adult↗
PubMed1994

A theory of the value of children.

This paper uses a non-standard value assumption--uncertainty reduction--to explain parenthood. We begin by reviewing the inadequacies of normative and standard rational choice explanations of shifts in fertility behavior. Then we propose a theory of the value of children based on the uncertainty-reduction assumption. Next we generate a range of hypotheses that follow both from this assumption and from a subsidiary assumption of marital solidarity enhancement. Finally, we explore the extent to which implications based on these new ideas are supported by the relevant empirical literature.

Adolescent↗
PubMed1993

Neonatal hemochromatosis associated with maternal autoantibodies against Ro/SS-A and La/SS-B ribonucleoproteins.

Liver disease in the fetus and neonate may be associated with maternal Sjögren's syndrome (neonatal lupus erythematosus). The infant of a mother with Sjögren's syndrome and high anti-Ro/SS-A and anti-La/SS-B antibody titers presented at 2 1/2 weeks of age with overwhelming hepatic insufficiency and died at 6 weeks of age. Autopsy confirmed the antemortem diagnosis of neonatal hemochromatosis. We discuss the possibility of a relationship between these two conditions.

Adult↗
PubMed1993

Identification of mothers at risk for congenital heart block and other neonatal lupus syndromes in their children. Comparison of enzyme-linked immunosorbent assay and immunoblot for measurement of anti-SS-A/Ro and anti-SS-B/La antibodies.

OBJECTIVE: To identify the fine specificity patterns of maternal anti-SS-A/Ro and anti-SS-B/La antibodies that are associated with the birth of a child with transient or permanent manifestations of neonatal lupus syndromes, and to suggest a predictor algorithm for use in counseling. METHODS: Sera were obtained from 4 groups of mothers: 57 whose children had congenital heart block, 12 whose children had transient dermatologic or hepatic manifestations of neonatal lupus but no detectable cardiac involvement, 152 with systemic lupus erythematosus and related autoimmune diseases, who gave birth to healthy infants, and 30 with autoimmune diseases whose pregnancy resulted in miscarriage, fetal death, or early postpartum death unrelated to neonatal lupus. Antibodies to SS-A/Ro and SS-B/La were assessed by enzyme-linked immunosorbent assay (ELISA) and by sodium dodecyl sulfate (SDS)-immunoblot. RESULTS: Anti-SS-A/Ro antibodies were identified by ELISA in 100%, 91%, 47%, and 43% of the mothers of infants with heart block, with transient neonatal lupus, healthy infants, and fetal death, respectively. High titers of anti-SS-A/Ro antibodies were present more often in mothers of children with cardiac disease or transient neonatal lupus than in either of the other 2 groups. Maternal antibodies to SS-B/La were detected by ELISA in 76% of the heart block group, 73% of the cutaneous neonatal lupus group, 15% of the group with healthy children, and 7% of the fetal death group. On SDS-immunoblot, sera from 91% of the heart block group mothers who had antibodies to SS-A/Ro but not to SS-B/La recognized at least 1 SS-A/Ro antigen, with significantly greater reactivity against the 52-kd component. In contrast, only 62% of the anti-SS-A/Ro positive, anti-SS-B/La negative responders in the healthy group recognized the 52-kd and/or the 60-kd component. Although there was no profile of anti-SS-A/Ro response unique to the mothers of children with heart block or cutaneous manifestations of neonatal lupus, only 1% of the healthy infants were born to mothers with antibodies directed to both the 52-kd SS-A/Ro and 48-kd SS-B/La antigens and not to the 60-kd SS-A/Ro antigen. CONCLUSION: Women with antibodies to both SS-A/Ro and SS-B/La have an increased risk of giving birth to children with neonatal lupus, especially if the anti-SS-A/Ro response identifies the 52-kd component on SDS-immunoblot. Women whose sera contain only anti-SS-A/Ro antibodies in low titer and only recognize determinants that are altered by conditions of SDS-immunoblot have a low risk for giving birth to a child with neonatal lupus. Specific antibody profiles do not distinguish among the manifestations of the neonatal lupus syndromes.

Animals↗