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Biomedical subjects

D Friedman

Publications and source records attributed to D Friedman.

At least 37 records · Page 2Linked to original sources
PubMed1999

Comparison of treatment with fluorinated glucocorticoids to the natural history of autoantibody-associated congenital heart block: retrospective review of the research registry for neonatal lupus.

OBJECTIVE: To compare intervention with fluorinated glucocorticoids to the natural history of untreated congenital heart block (CHB) with respect to conduction abnormalities, associated effusions, ascites, and hydrops fetalis, and the requirement for a pacemaker. METHODS: Records of all mothers enrolled in the Research Registry for Neonatal Lupus were reviewed. The cohort includes 47 mothers whose sera contain anti-SSA/Ro or anti-SSB/La antibodies, and their 50 offspring with CHB, in whom at least 4 echocardiograms were performed after in utero diagnosis. In 28 pregnancies, mothers received dexamethasone 4-9 mg/day for 3-19 weeks or betamethasone 12-24 mg/week for >6 weeks (group A). In 22 pregnancies, fluorinated steroids were not used (group B). RESULTS: Third-degree block was present in 21 fetuses in group A and 18 fetuses in group B; none were reversible despite steroid treatment. Three fetuses in group A and 2 in group B progressed from second-degree block, alternating with third-degree block, to permanent third-degree block at birth and postnatally. Of 4 fetuses in group A with second-degree block at presentation, all reverted to first-degree block by birth; 2 remain so at age 4 years, 1 alternates between first-degree and second-degree block at 2 years, and the fourth is in second-degree block at age 4 years. Of 2 fetuses in group B with second-degree block at presentation, both progressed to permanent third-degree block postnatally. Initial echocardiographic evaluation revealed pericardial effusions in 13 group A versus 4 group B fetuses, pleural effusions in 2 group A versus 0 group B, ascites in 8 group A versus 0 group B (P < 0.007), hydrops fetalis in 8 group A versus 0 group B (P < 0.007), and intrauterine growth restriction in 1 group A versus 1 group B. Pericardial effusions resolved and reappeared in both groups. Steroid therapy was most effective in the resolution of pleural effusions (2 of 2), ascites (6 of 8), and hydrops fetalis (5 of 8). Oligohydramnios ensued in 9 group A and 2 group B fetuses. Although fetuses in group A had more complications at presentation than those in group B, there were no significant differences in the duration of pregnancy (35.7 weeks versus 37.0 weeks), the number of deaths (4 versus 1), final degree of heart block, or requirement for a pacemaker (14 versus 11). CONCLUSION: While prospective trials are needed, these data suggest that fluorinated steroids should be considered for fetuses with incomplete block or hydropic changes. Serial echocardiograms are recommended to monitor fetal progress. It remains to be determined whether third-degree block is reversible if therapy is initiated immediately upon detection.

Autoantibodies↗
PubMed1999

Electrocardiographic repolarization abnormalities in familial dysautonomia: an indicator of cardiac autonomic dysfunction.

OBJECTIVE: Electrocardiographic repolarization intervals were evaluated to determine the extent of cardiac autonomic dysfunction in patients with familial dysautonomia (FD) and to determine if any of these intervals could serve as a possible predictor of clinical symptoms. METHODS: Thirty-seven electrocardiograms of patients with FD were retrospectively evaluated. QT, JT, rate-corrected QT and JT intervals were calculated as well as QT and QTC dispersion. Results were compared to normative data and electrocardiograms of 20 age-matched control subjects. OBSERVATIONS: In the FD group, prolongation of QTC (>450 msec) was noted in 5/37 (13.5%) patients, as compared to 0/20 normal controls (p = NS), and prolongation of JTc (>340 msec) in 16/37 (43.3%) patients, as compared to 0/20 normal controls (p < 0.001). QT and QTC dispersion were abnormal in 3/37 (8.1%) and 5/37 (13.5%), respectively. In the 16 FD patients with prolonged JTc, six had a positive history of syncope, whereas none of the 21 with normal JTc had syncope or symptoms suggesting arrhythmia (p < 0.003). The positive predictive value of having syncope or symptoms suggestive of arrhythmia with an abnormal JTc is 37.5% (95% CI [15%, 65%]). The negative predictive value is 100% (95% CI [87%, 100%]). CONCLUSION: In the FD population, the electrocardiographic measure of repolarization that was most frequently abnormal was the JTc interval . Prolongation of the JTc interval was significantly more frequent than prolongation of the QTC interval (p < 0.001) QT and QTC dispersions were less significantly affected in the FD population, indicating uniform ventricular recovery time. These results suggest that a prolonged JTc interval may be a more sensitive indicator of abnormal ventricular repolarization and cardiac autonomic dysfunction. Due to the known sympathetic denervation inherent in patients with FD, they are at risk for unopposed parasympathetic predominance. FD patients, therefore, are more likely to have brady arrhythmias and asystole rather than polymorphic ventricular tachycardia. The increased incidence of syncope in patients with prolonged JTc suggests that this measure may serve as a helpful marker to predict which FD patients are at increased risk of serious clinical sequelae including bradyarrhythmias with asystole or sudden death.

Adolescent↗
PubMed1999

Risk factors and outcomes following revascularization for chronic mesenteric ischemia.

Revascularization for chronic mesenteric ischemia is an infrequent vascular procedure whose objective long-term patency results have been described in relatively few patients. We reviewed our experience with such procedures and report on the objective and symptomatic long-term results. We retrospectively reviewed a consecutive series of 42 patients who underwent mesenteric arterial reconstruction of 66 vessels during an 11-year period from 1986 to 1997. All patients were treated for symptomatic chronic mesenteric ischemia. The results support the clinical efficacy and durability of visceral artery bypass procedures for patients with symptomatic chronic mesenteric ischemia. Patency rates for females were better than for males independent of graft type.

Angioplasty↗
PubMed1999

Brain event-related potentials (ERPs) in schizophrenia during a word recognition memory task.

Impairments of recognition memory for words and attenuation of the ERP 'old-new' effect have been found in patients with left medial temporal lobe damage. If left temporal lobe dysfunction in schizophrenia involves medial structures (e.g. hippocampus), then schizophrenic patients might show similar abnormalities of verbal recognition memory. This study recorded ERPs from 30 electrode sites while subjects were engaged in a continuous word recognition memory task. Results are reported for 24 patients having a diagnosis of schizophrenia (n = 16) or schizoaffective disorder (n = 8) and 19 age-matched healthy controls. Both patients and controls showed the expected 'old-new' effect, with greater late positivity to correctly recognized old words at posterior sites, and there was also no significant difference between groups in P3 amplitude. However, accuracy of word recognition memory was poorer in patients than controls, and patients showed markedly smaller N2 amplitude. Reduced amplitudes of N2 and N2-P3 were associated with poorer performance, with highest correlations over the left inferior parietal (N2) and left medial parietal (N2-P3) region. Moreover, patients failed to show significantly greater left than right hemisphere amplitude of N2-P3 at posterior sites, which was seen for healthy controls. These findings suggest that impaired word recognition in schizophrenia may arise from a left lateralized deficit at an early stage of processing, beginning at 200-300 ms after word onset.

Adult↗
PubMed1999

The effect of intention to learn novel, environmental sounds on the novelty P3 and old/new recognition memory.

Brain electrical activity was recorded while 32 young adults listened to frequent tones, infrequent target tones, and infrequent novel environmental sounds (some of which repeated). Subjects in the incidental group were not informed about the novel sounds, while subjects in the intentional group were informed and, in addition, were asked to memorize them for a subsequent memory test. Following the novelty oddball task, all subjects were given an old/new sound recognition memory task. The novelty P3 showed a more anterior scalp distribution and an effect of repetition in the incidental compared to the intentional group, suggesting that pre-categorizing the novel sounds influenced how they were processed. For the intentional group only, a subsequent memory effect was elicited by novel sounds that were subsequently recognized compared to those that were not, although both groups showed robust old/new ERP effects during the recognition task. The robust subsequent memory effects in the intentional group were associated with greater recognition accuracy of familiar environmental sounds relative to the incidental group. These data suggest that the encoding activity reflected in the ERP subsequent memory effect may have engendered an advantage in subsequent recognition memory performance.

Acoustic Stimulation↗
PubMed1999

Episodic priming and memory for temporal source: event-related potentials reveal age-related differences in prefrontal functioning.

Event-related potentials (ERPs) were recorded from young (M = 25) and older (M = 71) adults during a recognition memory paradigm that assessed episodic priming. Participants studied two temporally distinct lists of sentences (each with two unassociated nouns). At test, in response to the nouns, participants made old-new, followed by remember (context)-know (familiarity) and source (i.e., list) judgments. Both young and older adults showed equivalent episodic priming effects. However, compared to the young adults, the older adults showed a greater source performance decrement than item memory performance decrement. Both age groups showed equivalent posterior-maximal old-new ERP effects. However, only the young produced a frontal-maximal, late onset old-new effect that differed as a function of subsequent list attribution. Because source memory is thought to be mediated by prefrontal cortex, we conclude that age-related memory differences may be due to a deficit in a prefrontal cortical system that underlies source memory and are not likely to be due to an age-related decline in episodic priming.

Adult↗
PubMed1999

Analysis of the role of trans-translation in the requirement of tmRNA for lambdaimmP22 growth in Escherichia coli.

The small, stable RNA molecule encoded by ssrA, known as tmRNA or 10Sa RNA, is required for the growth of certain hybrid lambdaimmP22 phages in Escherichia coli. tmRNA has been shown to tag partially synthesized proteins for degradation in vivo by attaching a short peptide sequence, encoded by tmRNA, to the carboxyl termini of these proteins. This tag sequence contains, at its C terminus, an amino acid sequence that is recognized by cellular proteases and leads to degradation of tagged proteins. A model describing this function of tmRNA, the trans-translation model (K. C. Keiler, P. R. Waller, and R. T. Sauer, Science 271:990-993, 1996), proposes that tmRNA acts first as a tRNA and then as a mRNA, resulting in release of the original mRNA template from the ribosome and translocation of the nascent peptide to tmRNA. Previous work from this laboratory suggested that tmRNA may also interact specifically with DNA-binding proteins, modulating their activity. However, more recent results indicate that interactions between tmRNA and DNA-binding proteins are likely nonspecific. In light of this new information, we examine the effects on lambdaimmP22 growth of mutations eliminating activities postulated to be important for two different steps in the trans-translation model, alanine charging of tmRNA and degradation of tagged proteins. This mutational analysis suggests that, while charging of tmRNA with alanine is essential for lambdaimmP22 growth in E. coli, degradation of proteins tagged by tmRNA is required only to achieve optimal levels of phage growth. Based on these results, we propose that trans-translation may have two roles, the primary role being the release of stalled ribosomes from their mRNA template and the secondary role being the tagging of truncated proteins for degradation.

Adenosine Triphosphatases↗
PubMed1999

Scaling is necessary when making comparisons between shapes of event-related potential topographies: a reply to Haig et al.

A. R. Haig, E. Gordon, and S. Hook (1997) disputed G. McCarthy and C. C. Wood's (1985) contention that scaling should be used when assessing the statistical significance of between condition (or group) differences in the shapes of event-related potential (ERP) scalp topographies. Haig et al. based their contention upon the lack of empirical realism in McCarthy and Wood's model of within-group ERP noise, claiming that McCarthy and Wood's results could not be generalized to realistic ERP data. We argue, on both empirical and theoretical grounds, that Haig et al. do not make a compelling case against generalization of McCarthy and Wood's results. Moreover, Haig et al.'s conclusion is based upon a misconception of how scaling should be used. We conclude that when a quantitative measure of differences between topographic shapes is needed, scaling is not an option--it is a requirement.

Analysis of Variance↗
PubMed1998

Effect of sound familiarity on the event-related potentials elicited by novel environmental sounds.

The effect of sound familiarity was examined within the context of an event-related potential (ERP) novelty oddball paradigm. Brain electrical activity was recorded while subjects (16 young adults) listened to frequent tones, infrequent target tones, and infrequent novel environmental sounds. Subjects were instructed to press a button in response to the target tones only. There were 48 different novel sounds, 32 of which were repeated, and about two-thirds of which represented familiar sound concepts. The novel sounds elicited two ERP components, the novelty P3 and the P32. The novelty P3 was modulated by both repetition and familiarity, such that repeated familiar sounds elicited decreased novelty P3 amplitude at frontal sites, while repeated unfamiliar sounds elicited increased novelty P3 amplitude at posterior sites. This differential effect may reflect the operation of a neural network that distinguishes among different degrees of novelty.

Adult↗
PubMed1998

Broadening the Tests of Learning Models.

For many years psychological studies of the learning process have used a simulated medical diagnosis task in which symptom configurations are probabilistically related to diseases. Participants are given a set of symptoms and asked to indicate which disease is present, and feedback is given on each trial. We enrich this standard laboratory task in four different ways. First, the symptoms have four possible values (low, medium low, medium high, and high) rather than just two. Second, symptom configurations are generated from an expanded factorial design rather than a simple factorial design. Third, subjects are asked to make a continuous judgment indicating their confidence in the diagnosis, rather than simply a binary judgment. Fourth, cumulated performance scores, payoffs, and the availability of a historical summary of the outcomes are varied in order to assess how these treatments modulate performance. These enrichments provide a broader data set and more challenging tests of the models. Using 123 subjects each in 480 trials, we compare five existing learning models plus several variants, including the well-known Bayesian, fuzzy logic, connectionist, exemplar, and ALCOVE models. We find that the subjects do learn to distinguish the symptom configurations, that subjects are quite heterogeneous in their response to the task, and that only a small part of the variation across subjects arises from the differences in treatments. The most striking finding is that the model that best predicts subjects' behavior is a simple Bayesian model with a single fitted parameter for prior precision to capture individual differences. We use rolling regression techniques to elucidate the behavior of this model over time and find some evidence of over-response to current stimuli. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Biliopancreatic diversion.

Biliopancreatic diversion (BPD) has made reacceptable the malabsorptive approach to the surgical treatment of obesity. The procedure, in a series of 2241 patients operated on during a 21-year period, caused a mean permanent reduction of about 75% of the initial excess weight. The indefinite weight maintenance appears to be due to the existence of a threshold absorption capacity for fat and starch, and thus energy, and the weight loss is partly due to increased resting energy expenditure. Beneficial effects other than those consequent to weight loss or reduced nutrient absorption included permanent normalization of serum glucose and cholesterol without any medication and on totally free diet in 100% of cases, both phenomena being due to a specific action of the operation. Operative mortality was less than 0.5%. Specific late complications included anemia, less than 5% with adequate iron or folate supplementation (or both); stomal ulcer, reduced to 3.2% by oral H2-blocker prophylaxis; bone demineralization, increasing up to the fourth year and tending to decrease thereafter, with need of calcium and vitamin D supplementation; neurologic complications, totally avoidable by prompt vitamin B administration to patients at risk; protein malnutrition, which was reduced to a minimum of 3% with 1.3% recurrence, in exchange with a smaller weight loss, by adapting the volume of the gastric remnant and the length of the alimentary limb to the patient's individual characteristics. It is concluded that the correct use of BPD, based on the knowledge of its mechanisms of action, can make the procedure an effective, safe one in all hands.

Adolescent↗
PubMed1998

Pharmacokinetics of three once-weekly dosages of fluconazole (150, 300, or 450 mg) in distal subungual onychomycosis of the fingernail.

BACKGROUND: Fluconazole has proven to be safe and effective for a variety of superficial and systemic fungal infections. Preliminary analysis of extensive Phase III studies suggests that it is very effective for the treatment of onychomycosis. Its pharmacokinetic properties, including low molecular weight and high water-solubility, suggest a unique ability to penetrate the nail. This feature is likely to account in part for fluconazole's effectiveness in the treatment of onychomycosis. OBJECTIVE: Determinations of plasma and fingernail concentrations of fluconazole were performed as part of a larger study comparing the safety and efficacy of once-weekly fluconazole (150, 300, and 450 mg) to placebo in the treatment of distal subungual onychomycosis of the fingernails caused by dermatophytes. The relationship between fluconazole concentrations and efficacy was also examined. METHODS: Pharmacokinetic studies were performed by means of plasma and fingernail samples from 133 patients, a subset of 349 patients participating in a double-blind, placebo-controlled clinical trial of fluconazole administered in once-weekly doses of 150, 300, or 450 mg until cure of onychomycosis or for a maximum of 9 months. Blood and fingernail samples for pharmacokinetic analysis were taken at baseline, at week 2, and at monthly intervals during the treatment phase of the study. Patients considered clinically cured or improved also participated in a 6-month follow-up study. During this phase, patients were monitored and samples taken every 2 months. RESULTS: Significant amounts of fluconazole were detected in the earliest fingernail samples taken (after 2 weeks of treatment). After two weekly doses, 30% to 33% of steady-state concentrations had been achieved in healthy nails and 22% to 29% in affected nails. Steady state was achieved in 3 to 5 months. Fluconazole concentration in nails as well as plasma followed dose-proportional pharmacokinetics. Nail:plasma ratios in affected nails were 0.4 to 0.6 at 2 weeks and 1.7 to 1.8 at 6 months. Fluconazole concentrations fell slowly after drug discontinuation and were still detectable 4 months after end of treatment. A statistically significant correlation was found between steady-state concentration and clinical and global outcomes. CONCLUSION: Fluconazole rapidly penetrates the fingernail, where it is retained at detectable levels for at least 4 months after drug discontinuation. A significant correlation exists between fluconazole concentration in the fingernails and clinical and global outcomes.

Adult↗
PubMed1998

Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry.

OBJECTIVES: The present study describes the demographics, mortality, morbidity and recurrence rates of autoimmune-associated congenital heart block (CHB) using information from the Research Registry for Neonatal Lupus. BACKGROUND: Isolated CHB detected at or before birth is strongly associated with maternal autoantibodies to 48-kD SSB/La, 52-kD SSA/Ro and 60-kD SSA/Ro ribonucleoproteins and is a permanent manifestation of the neonatal lupus syndromes (NLS). Available data are limited by the rarity of the disease. RESULTS: The cohort includes 105 mothers whose sera contain anti-SSA/Ro or anti-SSB/La antibodies, or both, and their 113 infants diagnosed with CHB between 1970 and 1997 (56 boys, 57 girls). Of 87 pregnancies in which sufficient medical records were available, bradyarrhythmia confirmed to be CHB was initially detected before 30 weeks of gestation in 71 (82%) (median time 23 weeks). There were no cases in which major congenital cardiac anatomic defects were considered causal for the development of CHB; in 14 there were minor abnormalities. Twenty-two (19%) of the 113 children died, 16 (73%) within 3 months after birth. Cumulative probability of 3-year survival was 79%. Sixty-seven (63%) of 107 live-born children required pacemakers: 35 within 9 days of life, 15 within 1 year, and 17 after 1 year. Forty-nine of the mothers had subsequent pregnancies: 8 (16%) had another infant with CHB and 3 (6%) had a child with an isolated rash consistent with NLS. CONCLUSIONS: Data from this large series substantiate that autoantibody-associated CHB is not coincident with major structural abnormalities, is most often identified in the late second trimester, carries a substantial mortality in the neonatal period and frequently requires pacing. The recurrence rate of CHB is at least two- to three-fold higher than the rate for a mother with anti-SSA/Ro-SSB/La antibodies who never had an affected child, supporting close echocardiographic monitoring in all subsequent pregnancies, with heightened surveillance between 18 and 24 weeks of gestation.

Autoimmune Diseases↗
PubMed1998

Effects of aging on the novelty P3 during attend and ignore oddball tasks.

The effects of attention were assessed on novelty P3 amplitude and scalp distribution elicited by environmental sounds in young and elderly volunteers who participated in either actively attended or ignored oddball conditions. For the young, novelty P3 amplitude decreased with time on task during both attend and ignore sequences. Amplitude decrements were greatest at frontal sites during the attend condition, but at all sites during the ignore condition. A reliable amplitude decrement was not observed for the elderly in either the attend or ignore oddball series. The data suggest that attention differentially activates multiple generators that contribute to scalp-recorded novelty P3 activity. The lack of novelty P3 habituation seen in the elderly is consistent with changes in frontal lobe function as age increases.

Acoustic Stimulation↗
PubMed1998

Strengthening of horizontal cortical connections following skill learning.

Learning a new motor skill requires an alteration in the spatiotemporal pattern of muscle activation. Motor areas of cerebral neocortex are thought to be involved in this type of learning, possibly by functional reorganization of cortical connections. Here we show that skill learning is accompanied by changes in the strength of connections within adult rat primary motor cortex (M1). Rats were trained for three or five days in a skilled reaching task with one forelimb, after which slices of motor cortex were examined to determine the effect of training on the strength of horizontal intracortical connections in layer II/III. The amplitude of field potentials in the forelimb region contralateral to the trained limb was significantly increased relative to the opposite 'untrained' hemisphere. No differences were seen in the hindlimb region. Moreover, the amount of long-term potentiation (LTP) that could be induced in trained M1 was less than in controls, suggesting that the effect of training was at least partly due to LTP-like mechanisms. These data represent the first direct evidence that plasticity of intracortical connections is associated with learning a new motor skill.

Action Potentials↗
PubMed1998

Motor performance following a mild traumatic brain injury in children: an exploratory study.

Mild Traumatic Brain Injury (TBI) is a common occurrence in the paediatric population and, as the concept of motor performance has not been assessed specifically in this population, the purpose of this study was to determine if motor performance deficits are present and can be objectively identified in a sample of children having sustained a mild TBI (Glasgow Coma Scale score 13-15). Twenty-eight children aged between 5 and 15 years were recruited immediately post-trauma. Subjects were considered normal on standard neurological exam at the time of discharge. They were assessed 13-18 days post-trauma using the Bruininks-Oseretsky Test of Motor Proficiency, a norm referenced clinical standardized assessment tool. Compared to published norms, motor performance was significantly lower in domains of balance, response speed and running speed an agility (t-test p < 0.01), and significantly higher in domains of upper extremity coordination and visual motor control (t-test p < 0.01). Although excellent performance can be observed in domains requiring upper limb coordination, motor planning and execution of motor tasks, deficits in balance and response speed can be identified in a significant number of children even after mild TBI. More specific and sensitive evaluations are necessary to identify the exact nature of the problems and evaluate their functional impact on daily activities.

Adolescent↗
PubMed1998

Interleukin-15 augments superoxide production and microbicidal activity of human monocytes against Candida albicans.

Interleukin-15 (IL-15) is a newly described cytokine that shares biological activities with IL-2. We report here results demonstrating the ability of IL-15 to enhance superoxide production and antifungal activity of human monocytes. After 18 and 48 h of treatment with IL-15, human elutriated monocytes manifested enhanced superoxide production in response to either phorbol myristate acetate or opsonized Candida albicans blastoconidia. Similar results were obtained when monocytes were treated with IL-2, but to a lesser extent. Combination studies with IL-15 and IL-2 showed no additive or synergistic effects. Following incubation of monocytes with IL-15 for 18 h, there was no significant increase in mRNA transcripts for components of the NADPH oxidase complex, p40-phox, p47-phox, and gp91-phox, suggesting a posttranscriptional modulation of enhanced superoxide production. Antibodies against the gamma chain of the IL-2 receptor and, to a lesser extent, against the beta chain partially abrogated the IL-15-mediated enhanced superoxide production. Additionally, human monocytes showed enhanced killing activity against C. albicans after 18 h of incubation with IL-15 or IL-2, but this treatment did not enhance the ability of these cells to phagocytose the organism. In addition, the enhanced fungicidal activity seen after 18 h of treatment was no longer detectable after 48 h of cytokine treatment. Culture supernatants from the IL-15-treated monocytes were assayed for the presence of other proinflammatory cytokines. IL-15 treatment did not induce the release of detectable levels of tumor necrosis factor alpha, IL-1beta, or IL-12. Our results indicate that IL-15 upregulates the microbicidal activity of human monocytes against C. albicans.

Candida albicans↗