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Biomedical subjects

S Raskin

Publications and source records attributed to S Raskin.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cystic fibrosis in the Brazilian population: DF508 mutation and KM-19/XV-2C haplotype distribution.

We have used PCR amplification of DNA obtained from Guthrie cards to identify the DF508 mutation and correlate it with the allele frequencies at two polymorphic loci (XV-2C and KM-19) closely linked to the cystic fibrosis gene. The DNA came from 193 white Brazilian families affected by cystic fibrosis and living in five different states of Brazil. The distribution of the haplotypes derived from the DF508 and non-DF508 XV-2C/KM-19 genotypes indicates that 88% of the DF508 alleles are linked to haplotype B and suggests that high heterogeneity exists among the non-DF508 cystic fibrosis alleles occurring in different states. Our data can be used to compare linkage disequilibrium between Brazilians and other heterogeneous populations where the DF508 mutation frequency is low and where many different rare mutations account for the remaining recessive cystic fibrosis alleles.

Adolescent↗
PubMed1997

[Orthodontic contribution in sleep apnea].

This study details the role that the orthodontist can play, when faced with sleeping obstructive apneas and snoring phénomena. Of special importance are knowledge of cranio-facial growth, radiographic exam and cephalometric analysis: they mainly help to understand all the aspects of this specific syndrome, and reveal the interest for a neuro-orthodontic or a neuro-surgical orthodontic approach.

Adult↗
PubMed1996

Effects of integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina. A randomized multicenter trial.

BACKGROUND: Although aspirin is beneficial in patients with unstable angina, it is a relatively weak inhibitor of platelet aggregation. The effect of Integrelin, which inhibits the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter ischemia was evaluated in 227 patients with unstable angina. METHODS AND RESULTS: Patients received intravenous heparin and standard ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin. 45 micrograms/kg bolus followed by a 0.5 microgram.kg-1. min-1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 micrograms/kg bolus followed by a 1.0-microgram.kg-1, min-1 constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomized to high-dose Integrelin experienced 0.24 +/- 0.11 ischemic episodes (mean +/- SEM) on Holter lasting 8.41 +/- 5.29 minutes over 24 hours of study drug infusion. Patients randomized to aspirin experienced a greater number (1.0 +/- 0.33, P < .05) and longer duration (26.2 +/- 9.8 minutes, P = .01) of ischemic episodes than the high-dose Integrelin group. There was no evidence of rebound ischemia after withdrawal of study drug. In 46 patients, platelet aggregation was rapidly inhibited by Integrelin in a dose-dependent fashion. The number of clinical events was small, and there were no bleeding differences in the three treatment arms. CONCLUSIONS: Intravenous Integrelin is well tolerated, is a potent reversible inhibitor of platelet aggregation, and added to full-dose heparin reduces the number and duration of Holter ischemic events in patients with unstable angina compared with aspirin.

Adult↗
PubMed1996

Distinct 15q genotypes in Russell-Silver and ring 15 syndromes.

Individuals with a ring 15 chromosome [r(15)] and those with Russell-Silver syndrome have short stature, developmental delay, triangular face, and clinodactyly. To assess whether the apparent phenotypic overlap of these conditions reflects a common genetic cause, the extent of deletions in chromosome 15q was determined in 5 patients with r(15), 1 patient with del 15q26.1-qter, and 5 patients with Russell-Silver syndrome. All patients with Russell-Silver syndrome were diploid for genetic markers in distal 15q, indicating that Russell-Silver syndrome in these individuals was unlikely to be related to the expression of single alleles at these or linked genetic loci. At least 3 distinct sites of chromosome breakage close to the telomere were found in the r(15) and del 15q25.1-qter patients, with 1 r(15) patient having both a terminal and an interstitial deletion. Although the patient with del 15q25.1-qter exhibited the largest deletion and the most profound growth retardation, the degree of growth impairment among the r(15) patients was not correlated with the size of the deleted interval. Rather, the parental origin of the ring chromosome in several patients was associated with phenotypes that are also seen in patients with either Prader-Willi (PWS) or Angelman (AS) syndromes, conditions that result from uniparental expression of genes on chromosome 15. In fact, unequal representation of chromosome 15 alleles in 1 patient with r(15) suggests the possibility that a mosaic karyotype composed of the constitutional cell line and cell line(s) possibly deficient in the ring chromosome might be present. The PWS-like or AS-like phenotypes could be explained by postzygotic loss of the ring chromosome, leading to uniparental inheritance of the intact chromosome in some tissues of r(15) patients.

Abnormalities, Multiple↗
PubMed1996

Genetic mapping of the human pituitary-specific transcriptional factor gene and its analysis in familial panhypopituitary dwarfism.

We have analyzed the human pituitary-specific transcription factor (Pit-1) gene using PCR amplification of DNA fragments that span intron III and contain portions of exons III and IV. A PCR restriction fragment length polymorphism (PCRFLP) was detected in intron III by RsaI digestion, which was used to assign the human Pit-1 locus to chromosome 3p by linkage analysis of the CEPH panel. Analysis of corresponding Pit-1 segments from six nonrelated probands with familial panhypopituitary dwarfism (FPD) did not reveal any alterations in size and co-segregation of Pit-1, or a tightly linked microsatellite marker (D3S1559), and FPD was excluded in all six kindreds. Our data (1) assign Pit-1 to human chromosome 3p by linkage, (2) provide a PCRFLP and identify a variety of tightly linked markers, for analysis of FPD, and (3) exclude Pit-1 defects as the basis of at least one form of FPD.

Alleles↗
PubMed1995

Modality dependent changes in event-related potentials correlate with specific cognitive functions in nondemented patients with Parkinson's disease.

The relationship between event-related potentials (ERPs) and cognitive functioning was studied in patients with Parkinson's Disease (PD) but without dementia. Auditory and visual stimuli were used; 30 subjects participated in the auditory study and 20 in the visual study. Patient groups did not differ with respect to gender, age, education, illness duration, and level of cognitive functioning. Visual stimuli were 2.3 cpd sinusoidal grating patterns randomly presented in an oddball paradigm (oblique vs. vertical spatial orientation). Auditory stimuli were tones presented at 70 dB SPL at a rate of 1.1/second, also using the oddball paradigm (1.5K vs. 1K tones). All patients were given neuropsychological tests to measure verbal fluency, memory, visual spatial perception, and abstract reasoning. P300 and N200 abnormalities correlated with a number of these measures, such that longer ERP latencies were related to lower scores on tests of cognitive functioning. Patterns of results suggest that auditory and visual ERPs correlate with different subsets of neuropsychological functions in nondemented PD patients and that N200 may provide a new metric for clinical use.

Cognition↗
PubMed1993

DNA analysis of cystic fibrosis in Brazil by direct PCR amplification from Guthrie cards.

A 3 bp deletion of codon 508 (phenylalanine) of the cystic fibrosis (CF) gene constitutes the mutation of most CF chromosomes. The frequency of this mutation (referred to as delta F508), varies considerably between populations, ranging from 26% of the CF mutations in Turkey to 88% in Denmark. To determine the frequency of the delta F508 mutation in Brazilian Caucasoid CF patients, we used direct polymerase chain reaction (PCR) amplification of DNA obtained from dried blood spots on Guthrie cards, followed by ethidium bromide staining of gels. Although the overall frequency of the delta F508 mutation was 47% of 380 CF chromosomes from Brazilian Caucasoids born in five different states, significant interstate differences were observed, ranging from a delta F508 frequency of 27% to 53%. While our method could be used to screen patients and their relatives for carrier testing and prenatal diagnosis, the efficacy of screening only for the delta F508 mutation would be low, and would vary from state to state. Screening for a panel of local mutations will be needed to increase the mutation detection rate and optimize genetic counseling.

Base Sequence↗
PubMed1993

Deep hypothermia with circulatory arrest. Determinants of stroke and early mortality in 656 patients.

We have retrospectively evaluated our results after aortic surgery in adults using deep hypothermia with circulatory arrest to determine the patient predictors of early death and postoperative stroke by logistic regression analysis. Of the 656 patients operated on between July 7, 1979, and January 30, 1991, 43% (n = 283) were female, the median age of the patients was 64 years (range 10 to 88 years), 12% (n = 77) had acute dissection, 26% (n = 173) had previously undergone either cardiac or ascending aortic operations, and 13% (n = 85) had a history of cerebrovascular disease. Eighty-four patients underwent elephant trunk procedures. The median circulatory arrest time was 31 minutes (range 7 to 120 minutes). The univariable predictors of transient or permanent stroke, defined as clinical evidence of neurologic injury, either global or hemiparetic, which occurred in 44 patients (7%), were as follows (p < 0.05): increased age; a history of cerebrovascular disease; circulatory arrest time (7 to 29 minutes = 12/298 [4%], 30 to 44 minutes = 15/201 [7.5%], 45 to 59 minutes 9/84 [10.7%], 60 to 120 minutes 7/48 [14.6%]; cardiopulmonary bypass time; and concurrent descending thoracic aorta repair. The multivariably determined predictors were as follows (p < 0.05): a history of cerebrovascular disease; previous aortic surgery distal to the left subclavian artery; and cardiopulmonary bypass time. A history of aortic valve incompetence, however, was associated with a lower risk of stroke (adjusted odds ratio 0.42, p = 0.015). The multivariably determined predictors for increased risk of early death (p < 0.05), which occurred in 66 (10%) patients, were as follows: increased age; Marfan syndrome; concurrent distal aortic aneurysm; previous ascending aortic operation; cardiopulmonary bypass time; cardiac complications; renal complications; and stroke. In this study, the occurrence of stroke was observed to increase after 40 minutes of circulatory arrest; furthermore, the mortality rate increased markedly after 65 minutes of circulatory arrest. Thus the "safe" period for strokes not developing appeared to be limited to approximately 40 minutes. We conclude that deep hypothermia with circulatory arrest is a safe technique for the repair of complex aortic problems provided both the circulatory arrest and the cardiopulmonary bypass times are not excessive. In addition, the clinical characteristics of the patients are important determinants of stroke and death.

Actuarial Analysis↗
PubMed1993

Estimation of the incidence of a rare genetic disease through a two-tier mutation survey.

Recent attempts to detect mutations involving single base changes or small deletions that are specific to genetic diseases provide an opportunity to develop a two-tier mutation-screening program through which incidence of rare genetic disorders and gene carriers may be precisely estimated. A two-tier survey consists of mutation screening in a sample of patients with specific genetic disorders and in a second sample of newborns from the same population in which mutation frequency is evaluated. We provide the statistical basis for evaluating the incidence of affected and gene carriers in such two-tier mutation-screening surveys, from which the precision of the estimates is derived. Sample-size requirements of such two-tier mutation-screening surveys are evaluated. Considering examples of cystic fibrosis (CF) and medium-chain acyl-CoA dehydrogenase deficiency (MCAD), the two most frequent autosomal recessive disease in Caucasian populations and the two most frequent mutations (delta F508 and G985) that occur on these disease allele-bearing chromosomes, we show that, with 50-100 patients and a 20-fold larger sample of newborns screened for these mutations, the incidence of such diseases and their gene carriers in a population may be quite reliably estimated. The theory developed here is also applicable to rare autosomal dominant diseases for which disease-specific mutations are found.

Acyl-CoA Dehydrogenase↗
PubMed1992

Cystic fibrosis genotyping by direct PCR analysis of Guthrie blood spots.

In the United States the most common cystic fibrosis (CF) alleles known are F508, G551D, G542X, R553X, and N1303K. These mutations comprise approximately 85% of U.S. CF alleles, and their detection along with analysis of XV-2C and KM-19 restriction fragment length polymorphisms (RFLPs) can enable the determination of CF status. To facilitate studies for determining CF carrier status, we developed methods to detect each of these mutations and RFLPs by direct PCR amplification of dried blood spots collected on newborn screening (Guthrie) cards. Following collection, samples were protected from contamination by individual plastic bags. One-mm2 segments of filter paper were added directly to 100-microliters PCR reactions containing 1/16 mM spermidine. Three initial cycles at 96 degrees C, then 55 degrees C, for 3 min were performed to free DNA and minimize inhibition by other related materials. Next, 1 unit of Taq polymerase was added and a 2-min extension was carried out at 72 degrees C, followed by 33 amplification cycles using denaturing, annealing, and extension temperatures and times optimal for each primer set. Then, 35 microliters of each reaction was run on 8% acrylamide gels directly or 1% agarose gels following digestion; genotypes were inferred by ethidium bromide staining of gels. Guthrie blood spots of 250 CF probands and their parents were screened and the frequencies of all five mutations as well as the XV-2C KM-19 RFLP haplotypes were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1992

Utility of internal markers to improve the accuracy of cystic fibrosis genotype analysis.

DNA diagnostic tests often utilize restriction endonuclease digestion of PCR-amplified portions of genes under analysis. When partial digestion occurs, the resulting patterns may lead to error in diagnosis. To overcome such potential errors in cystic fibrosis testing, we have developed internal markers that can increase the precision and reliability of genotype assignments.

Cystic Fibrosis↗
PubMed1991

[Obstructive sleep apnea syndrome: the orthodontist's viewpoint].

Obstructive sleep apnea syndrome (OSAS), previously called Pickwickian syndrome is usually associated with obesity, excessive daytime sleepiness and ventilation troubles. These patients are heavy snorers and present a typical craniofacial morphology. Among several characteristics is retrognathic lower maxillary. Functional orthodontic appliances are proposed to help these patients, in order to open the superior airway and allow a better ventilation.

Facial Bones↗
PubMed1990

The auditory P 300 correlates with specific cognitive deficits in Parkinson's disease.

An abnormally prolonged latency of the P 300 event-related potential has been reported in several types of dementing illnesses, including Parkinson's disease (PD). While some PD patients have dementia, a significant number of PD patients have less severe cognitive impairments. We examined the relationship between the auditory P 300 and a neuropsychological battery of 11 tasks in 43 PD patients. The quantitative relationship between the individual neuropsychological measures and the P 300 was examined using partial correlation and analysis of covariance techniques which controlled for age, education, and illness duration. The strongest correlations were between P 300 and both short-term memory and visual perception. Global cognitive deficits do not appear to relate to the abnormal P 300 responses in PD: instead, specific aspects of cognitive decline accounted for the electrophysiological abnormalities. An abnormally long or absent P 300 correlated with deficits on select cognitive tasks: those involving memory, visual perception, and abstract reasoning. The interactions between anatomical and neurochemical abnormalities in PD are discussed in light of the pattern of deficits seen in this study.

Adult↗
PubMed1980

Unusual complications of epicardial pacemakers. Recurrent pericarditis, cardiac tamponade and pericardial constriction.

Three patients with unusual complications after insertion of an epicardial pacemaker are described. In one patient pericarditis and severe cardiac tamponade developed that required emergency pericardiocentesis 8 weeks after pacemaker insertion. No evidence of myocardial perforation was observed at operation. In another patient two unusual complications developed: (1) migration of the pulse generator from the epigastric site of implantation into the pelvis, and (2) recurrent pericarditis with occult signs of constriction. In another patient recurrent pericarditis and clinical evidence of constriction developed. All three patients required pericardiectomy. Recurrent pericarditis after insertion of an epicardial pacemaker requires careful medical follow-up because either life-threatening tamponade or chronic constrictive pericarditis may develop.

Adult↗
PubMed1979

Determination of His-Purkinje refractoriness in man with His bundle pacing.

Consistent His bundle pacing was accomplished in one of 60 consecutive patients. Intracardiac electrophysiologic studies in this patient revealed rapid atrioventricular nodal conduction (AH = 55 msec). While the relative refractory period of the His-Purkinje system as a whole determined by His bundle pacing (using the extrastimulus technique) was identical to that determined by atrial pacing, changes in right bundle branch refractoriness differed. An atrial extrasystolic interval of 370 msec resulted in right bundle branch block, whereas direct His pacing at a shorter extrasystolic interval (360 msec) failed to produce a bundle branch block pattern. The effective refractory period of the His-Purkinje system could not be determined by atrial pacing because of atrial refractoriness, but was obtained by His bundle pacing. Theoretically, direct His bundle pacing may be of value in determining His-Purkinje system refractoriness when this parameter is unobtainable due to either atrial or atrioventricular nodal refractoriness. This technique appears to have limited clinical usefulness, however, because of the very small success rates. Finally, His-Purkinje system refractoriness may differ, depending on site of stimulation, presumably due to differing inputs into the His-Purkinje system.

Adult↗