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Biomedical subjects

M H Crawford

Publications and source records attributed to M H Crawford.

At least 19 recordsLinked to original sources
PubMed2005

Applications of pooled DNA samples to the assessment of population affinities: short tandem repeats.

Pooled DNA samples have been used in association studies of Mendelian disease genes. This method involves combining equal quantities of DNA from patients and control subjects into separate pools and comparing the pools for distributions of genetic markers. In this study identical quantities of DNA from 300 individuals representing 6 populations were pooled and amplified for 296 loci using the touchdown polymerase chain reaction (PCR) method. The purpose of this study is to test the efficacy of pooled DNA markers in the reconstruction of the genetic structure of human populations. The populations sampled included Chuvash, Buryats, Kizhi, Native Americans, South Africans, and New York City whites. To test the accuracy of the allele-frequency distributions, we genotyped the Buryats and New York samples individually for six microsatellite markers and compared their frequencies to the allele frequencies derived from the electropherogram peak heights for the pooled DNA, producing a correlation of 0.9811 with a variance of less than 0.04. Two-dimensional scaling of genetic distances among the six populations produced clusters that reflected known historical relationships. A distance matrix was created using all 296 loci, and matrices based on individual chromosomes were correlated against the total matrix. As expected, the largest chromosomes had the highest correlations with the total matrix, whereas one of the smallest chromosomes, chromosome 22, had the lowest correlation and differed most from the combined STR distance matrix.

Alleles↗
PubMed2004

Mid-ultraviolet light-emitting diode detects dipicolinic acid.

Dipicolinic acid (DPA, 2,6-pyridinedicarboxylic acid) is a substance uniquely present in bacterial spores such as that from anthrax (B. anthracis). It is known that DPA can be detected by the long-lived fluorescence of its terbium chelate; the best limit of detection (LOD) reported thus far using a large benchtop gated fluorescence instrument using a pulsed Xe lamp is 2 nM. We use a novel AlGaN light-emitting diode (LED) fabricated on a sapphire substrate that has peak emission at 291 nm. Although the overlap of the emission band of this LED with the absorption band of Tb-DPA (lambda(max) doublet: 273, 279 nm) is not ideal, we demonstrate that a compact detector based on this LED and an off-the-shelf gated photodetection module can provide an LOD of 0.4 nM, thus providing a basis for convenient early warning detectors.

Aerosols↗
PubMed2001

Genetic variation among the Golla pastoral caste subdivisions of Andhra Pradesh, India, according to the HLA system.

The HLA allele frequency distributions have been characterized for the HLA class I and class II loci of the Golla pastoral caste, from Southeast India, subdivided into the subcastes (Puja, Punugu, Kurava, Pokanati, Karnam, and Doddi). Genetic distances, neighbor-joining, correspondence, and haplotype analyses all indicate that the subcastes exhibit a high haplotype variability and that their genetic substratum may be the result of European-Middle East/Asian admixture with the autochthonous populations. The Karnam subcaste seems to be the one that has undergone a higher degree of admixture, when compared with the other subcastes. The Golla speak an old Indian Dravidian language and should theoretically represent the basic Indian substratum that existed before the postulated "Aryan" invasion.

Adult↗
PubMed2001

Heart failure disease management in an indigent population.

BACKGROUND: Multidisciplinary disease management programs (MDMP) have demonstrated reduced hospitalizations in motivated pretransplant heart failure populations, but little is known about their effectiveness in largely indigent patients who are not transplant candidates. METHODS AND RESULTS: We studied 35 patients with heart failure with left ventricular ejection fraction (EF) </=45% enrolled in an MDMP who were either indigent or funded by Medicaid/Medicare. This nonrandomized sample consisted of 14 patients identified because they had hospital readmission rates of >/=2 per year (group A) and 21 patients referred by their primary care physicians because they were difficult to manage (group B). Group A patients were New York Heart Association (NYHA) class III or IV, aged 25 to 87 years (mean 57 +/- 17 SD) and had an EF of 15% to 45% (29% +/- 11%). Group B patients were NYHA class II or III, aged 35 to 86 (57 +/- 16) years and had an EF of 20% to 45% (28% +/- 10%). Data were compared for the year before enrollment in the MDMP and the year afterward. In group A hospital admissions decreased from 33 to 3, a 91% reduction, and NYHA class improved to class II-III (P <.001). In group B hospital admissions decreased from 9 to 0, and NYHA class improved to class I-II (P <.001). When hospital and clinic charges were assessed for both groups, the net savings were $162,000 per year or $4600 per patient. CONCLUSIONS: A multidisciplinary heart failure program can improve functional status and reduce hospitalization and net costs compared with conventional care in indigent non-transplant candidate patients.

Adult↗
PubMed2001

Prevalence of heart disease in asymptomatic chronic cocaine users.

To determine the prevalence of heart disease in outpatient young asymptomatic chronic cocaine users, 35 cocaine users and 32 age-matched controls underwent resting and exercise electrocardiography (ECG) and Doppler echocardiography. Findings consistent with coronary artery disease were detected in 12 (34%) patients and 3 (9%) controls (p = 0.01). Decreased left ventricular systolic function was demonstrated in 5 (14%) patients, but in none of the controls (p = 0.055). Finally, resting and peak exercise abnormal left ventricular filling was detected in 38 and 35% of patients as compared to 19 and 9% of controls, respectively (p = 0.11 and 0.02, respectively). We conclude that coronary artery or myocardial disease is common (38%) in young asymptomatic chronic cocaine users. Therefore, screening ECG and echocardiography may be warranted in these patients.

Adult↗
PubMed2001

Genomic diversity at thirteen short tandem repeat loci in a substructured caste population, Golla, of southern Andhra Pradesh, India.

Genomic diversity based on 13 short tandem repeat (STR) loci was studied in seven population groups of a substructured Golla caste from Chittoor district in southern Andhra Pradesh, India. These groups are traditionally pastoral, culturally homogeneous, and strictly endogamous. Blood samples were drawn from 317 individuals from 30 Golla villages. The 13 STR loci analyzed in five standard multiplex polymerase chain reactions were: (1) CSF1R, TH01, and PLA2A; (2) F13A1, CYP19, and LPL; (3) D21S1446 and D21S1435; (4) D20S481, D20S473, and D20S604; and (5) D5S1453 and D6S1006. The average heterozygosity was found to be low among the Golla subgroups (0.64-0.70) in comparison to that of groups at the upper levels of the hierarchy. The coefficient of gene differentiation was found to be moderate (average GST = 0.031; range between 0.018 and 0.049 among the loci) when compared to that observed for a similar class of markers among populations with relatively higher levels of hierarchy, for example, among castes. It is, however, much higher when compared to the average observed for Indian caste and tribal populations, based on classical markers. Genetic distance measures revealed clusters of populations that are consistent with the known ethnohistorical and geographical backgrounds of the groups. We claim that these hypervariable markers are quite useful in understanding the process of substructuring within the Indian castes, leading to the formation of smaller breeding isolates, the basic Mendelian units within which microevolutionary forces operate.

Consanguinity↗
PubMed2001

Population substructure and patterns of quantitative variation among the Gollas of southern Andhra Pradesh, India.

Population substructure and biological differentiation was studied among the Golla, a pastoral caste living in the southern areas of Andhra Pradesh (AP) in India, using 11 anthropometric measurements and 20 quantitative dermatoglyphic variables. The data were collected from a sample of 334 adult males drawn from 30 villages distributed in the Chittoor district of AP, who belonged to 8 endogamous subunits of the same caste. Multiple discriminant analysis of the anthropometrics suggests a highly significant degree of discrimination that is consistent with the microgeographic variations of the groups. In contrast, in different sets of dermatoglyphs discrimination is low and generally inconsistent with both the geographic and ethnohistorical affiliations of the groups. These findings are reflected in the F(ST) value for anthropometry, which is more than double the value of dermatoglyphs. The patterns of gene flow as inferred through the regression of phenotypic variance on the distance of groups from the centroid is not generally consistent with the known backgrounds in the case of either dermatoglyphs or anthropometry. It is concluded that at the level of caste substructure representing the lowest level of population hierarchy, the quantitative variables examined here may not portray a complete picture of the historical process of subdivision. The results of this study are not in congruence with those based on another study of 13 short tandem repeat loci on the same set of populations (Reddy et al. 2001), which may provide better insights into the population structure and history of subdivision that are consistent with the known ethnohistorical backgrounds of the populations.

Adult↗
PubMed2001

Genetic structure of Mongolic-speaking Kalmyks.

Genetic polymorphisms of blood groups ABO and RH D, serum proteins HP, TF, and GC, and red cell enzymes ACP1, PGM1, ESD, GLO1, and SOD-A have been reported for three tribes (Torguts, Derbets, and Buzavs) of the Volga's Kalmyk-Oyrats. The Kalmyks exhibit genetic markers that are characteristic of Central Asian populations, namely, high allelic frequencies for ABO*B, TF*C2, GC*IF, ESD*2, and GLO1*2, and the rare incidence of individuals with the RH-negative phenotype. Genetic distance measures reveal that close genetic affinities exist between the Derbets and Buzavs, but both populations differ significantly from the Torguts. Collectively as an ethnic group, the Kalmyks genetically resemble the contemporary Buryats of the Baikal region of southeastern Siberia and the Mongols of Mongolia. The transplantation of the Kalmyk-Oyrats from their homeland near Lake Baikal to their current residence (4500 km) near the Caspian Sea and their subsequent isolation for more than 300 years have not appreciably altered the gene frequencies from the parental populations for frequencies of standard genetic markers.

Alleles↗
PubMed2000

Echocardiographic predictors of survival in low gradient aortic stenosis.

Echocardiographic predictors of long-term survival for patients with low gradient aortic stenosis who undergo aortic valve replacement have not been previously reported. This study shows that patients with larger pre- and postoperative left ventricular volumes, a lower mean preoperative aortic pressure gradient, and failure of volumes to decrease and ejection fraction to increase postoperatively may have a poor prognosis.

Adult↗
PubMed2000

Adoptive and biological families of children and adolescents with ADHD.

OBJECTIVE: Using an adoption study design, the authors addressed the issue of genetics in attention-deficit hyperactivity disorder (ADHD). METHOD: This study examined the rates of ADHD and associated disorders in the first-degree adoptive relatives of 25 adopted probands with ADHD and compared them with those of the first-degree biological relatives of 101 nonadopted probands with ADHD and 50 nonadopted, non-ADHD control probands. RESULTS: Six percent of the adoptive parents of adopted ADHD probands had ADHD compared with 18% of the biological parents of nonadopted ADHD probands and 3% of the biological parents of the control probands. CONCLUSION: Results of this study lend support to the hypothesis that ADHD has a genetic component.

Adolescent↗
PubMed2000

Distribution of the 3' VNTR polymorphism in the human dopamine transporter gene in world populations.

A polymorphism with a variable number of tandem repeats (VNTR) found in the 3' untranslated region of the human dopamine transporter gene (DAT1) was scored in unrelated individuals drawn from 10 geographically widely dispersed populations in order to assess this marker's usefulness in human population genetics. The populations that were analyzed in this study included 4 indigenous groups of Siberia, natives of North and South America, as well as Caucasian and Oceanic groups, most of which represented small-scale societies. A total of 5 DAT1 alleles were seen overall, but only in one Siberian population, the Altai-Kizhi, were all 5 present, and in the Native Americans of Colombia the locus was monomorphic. The most common allele, DAT1*10, ranged in frequency from 52% in Greeks to 100% in South Americans. The high frequency of the DAT1*10 allele (approximately 90%) among Mongoloid groups of north and east Asia distinguishes them from most Caucasian groups. The presence of the rare DAT1*7 allele in relatively high frequency (approximately 5%) among all Siberian groups suggests a close affinity with north Asian groups, especially Mongolians. The presence of the even rarer DAT1*13 allele in one Siberian population, the Altai-Kizhi, reflects this group's long historical contact with Mongolians. The results demonstrated that the DAT1 VNTR polymorphism is useful in investigating population relationships, and that rare alleles at this locus may be particularly valuable in understanding the extent of genetic affinity between neighboring groups and in situations where admixture is suspected. However, because of both the association and linkage of this VNTR locus with attention-deficit hyperactivity disorder (ADHD) in children, and its highly restricted polymorphism (usually 3 alleles) in most human groups, the possibility of selection constraints on the DAT1 gene cannot be ignored.

Female↗
PubMed2000

Phylogenetic relationships of human populations in sub-Saharan Africa.

This study utilizes the GM/KM immunoglobulin allotype system to elucidate the phylogenetic relationships of sub-Saharan Africans. The importance of understanding the relatedness of these peoples stems from the sub-Saharan region being the possible birthplace of humans. Haplotype distributions were determined for 19 populations and compared using chi-square analysis. Published data of other sub-Saharan Africans and representative populations worldwide were also added for comparison. Genetic distances between populations were calculated based on haplotype frequencies, and genetic relationships were observed through principal components analysis. Data from the GM/KM system showed a genetic homogeneity of the Bantu populations, with some exceptions, supporting the possibility of a common origin of these peoples. The Malagasy appeared as a divergent population, most likely due to Southeast Asian/Austronesian admixture, as indicated by the presence of the GM*AF B haplotype. The Cape Coloured also showed a divergence, with their genetic structures containing Caucasoid and Khoisan contributions. Finally, the Mbuti Pygmies appeared genetically isolated and had the highest frequency of the GM*A B haplotype out of all studied populations.

Africa South of the Sahara↗
PubMed2000

The population structure of ten Newfoundland outports.

Island populations are most informative in the study of the genetic structure of human aggregates. These populations are often of small size, thus violating the Hardy-Weinberg assumption of infinite size. Some geographically isolated island populations are further subdivided by religion, ethnicity, and socioeconomic factors, reducing their effective sizes and facilitating genetic changes due to stochastic processes. Because of extreme geographic and social isolation, fishing communities or outports of Newfoundland have been investigated for genetic microdifferentiation through the founder effect and genetic drift (Crawford et al. 1995). The purpose of this paper is to examine the population structure of 10 Newfoundland outports using the allelic frequencies derived from 12 red cell antigens. To achieve this goal, first we calculated gene frequencies using maximum-likelihood estimation procedures. Second, we used R-matrix methods to explore population differentiation. Third, we regressed mean per-locus heterozygosity on genetic distance from the gene frequency centroid to identify the most isolated populations. On the basis of this information, the three outports of Seal Cove, Island Harbor, and Tilting were found to be genetically differentiated from the other small populations. Moreover, religious and geographic subdivisions appear to explain the observed genetic variation.

Blood Group Antigens↗
PubMed1999

"Traditional" medical therapy for unstable angina. How important? How to use?

Unstable angina comprises a heterogeneous population of patients who present with a wide spectrum of underlying pathophysiology. The traditional treatment of these patients is based on both evidenced-based medicine as well as clinical experience. Despite the large population of patients admitted with this diagnosis, the scientific literature regarding its treatment is scarce. Therefore, the management of patients with unstable angina relies heavily on the clinical skills of the physician. One of the most important steps in this process involves risk stratification, especially in the current environment of cost containment. Those patients who are at low risk for adverse outcomes can be treated and evaluated safely as outpatients. Patients at high or moderate risk, however, should be treated intensively as inpatients. Although there appear to be many new promising therapies for unstable angina on the horizon, the traditional therapies still have a place. The use of aspirin in this population is well supported by the literature and appears to have a positive effect on mortality and cardiovascular events. The other traditional therapies, however, are not as well supported by the literature. They do appear to benefit the patient in terms of reducing symptoms, but their effects on reducing mortality and cardiovascular events are not clear. Therefore, the goal of medical therapy in this patient population should be to stabilize them so that they can proceed with an appropriate risk stratification procedure as soon as possible. This is especially true with performing coronary angiography or interventions because the risk of procedural complications is higher in patients with unstable angina and ongoing symptoms.

Adrenergic beta-Antagonists↗