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Pharmacogenomic diversity in Amazonian Indigenous populations: implications for Berlin-Frankfurt-Münster acute lymphoblastic leukemia therapy.

PURPOSE: This study aimed to characterize pharmacogenomic variation in genes involved in the metabolism and transport of drugs used in Berlin-Frankfurt-Münster-based therapy in Amazonian Indigenous individuals and to compare allele frequencies with major continental populations. METHODS/PATIENTS: Whole-exome sequencing data previously generated from 64 healthy Indigenous individuals from 12 Amazonian ethnic groups were analyzed. A total of 120 genes associated with drugs used in Berlin-Frankfurt-Münster protocols were selected. Variants were annotated and filtered using bioinformatic quality-control criteria, and allele frequencies were compared with African, Admixed American, East Asian, European, and South Asian populations from the 1000 Genomes Project. Multidimensional scaling was used to assess population-level genetic similarity. RESULTS: After quality control, 648 variants were identified. Twenty-eight variants were observed exclusively in the Indigenous study population, including four nonsynonymous coding variants with moderate predicted impact. Significant allele-frequency differences were observed for ADA rs11555566, CBR3 rs881711, and CYP2B6 rs3745274; rs881711 and rs3745274 differed from all five reference populations. Multidimensional scaling showed a distinct Indigenous pharmacogenomic profile, with greater similarity to the Admixed American population. CONCLUSIONS: Amazonian Indigenous populations exhibit substantial pharmacogenomic diversity in genes relevant to Berlin-Frankfurt-Münster-based therapy. These findings identify candidate variants for functional and clinical validation and reinforce the importance of including underrepresented populations in pharmacogenomic research.

Acute lymphoblastic leukemia

Cancer of asians in kenya.

The frequency of various cancers among Indian immigrants in Kenya was compared to corresponding data among native Africans and Indians in the regions of India from which most of the studied population originally migrated. The Kenyan Indians do not have the cancer pattern of their home country nor do they have the cancer pattern of indigenous Africans. They have instead, like Europeans and North Americans, a higher risk of cancer of the lung, breast and the large intestine. It is suggested that this is related to enbironmental factors and variations in living habits.

Female

The possible dream: the Navajo Nation Health Foundation.

The dream of high-quality health care for the Navajo began in Ganado, AZ, some 70 years ago. Now it has gone a step further through the work of the only hospital and clinic system in the United States that is owned and operated by American Indians.

Arizona

Current knowledge in pharmacogenomics and precision medicine: perspectives of the PGRN global PGx committee on improving drug therapies in underrepresented ethnic populations.

A precision medicine strategy is likely to be more impactful, when pharmacogenomics (PGx) guided selection of drugs and dosage wherever applicable is implemented across the globe. In regions where resources are disproportionately distributed, PGx implementation in routine clinical care can play a critical role in ensuring the optimal use of limited healthcare infrastructure. At present, PGx data from the majority of the distinct ethnic populations across Asia, Africa, and South America is limited. While international consortia, working groups, and scientific bodies have made significant contributions toward evaluating the evidence for PGx implementation, the majority of existing guidelines and recommendations are derived primarily from studies conducted in a limited number of ethnic groups. Precision Medicine Initiatives in countries like Korea, Taiwan, and Malaysia and PGx organizations like the African Institute of Biomedical Science and Technology (AiBST), Consortium for Genomics & Therapeutics in Africa (CGTA), implementation of pharmacogenetic testing for the effective care and treatment in Africa, Greater Middle East (GME) whole exome sequencing program, Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF), Latin American Society of Pharmacogenomics and Personalized Medicine (SOLFAGEM), Latin American Network for Validation and Implementation of Pharmacogenomic Clinical Guidelines (RELIVAF), IndiGen initiative, Southeast Asian Pharmacogenomics Research Network (SEAPharm), are working toward consolidating the PGx presence in these regions.

Precision Medicine

Absence of Anaplasma marginale infection in American Bison raised in an anaplasmosis endemic area.

Blood was collected at slaughter from 132 adult American bison (Bison bison) raised in an anaplasmosis endemic area where the vector Dermacentor andersoni (equals venustus) is indigenous. Hematologic studies revealed no indication of clinical anaplasmosis. Card agglutination and complement-fixation tests on all bison serums were negative. Eleven anaplasmosis-susceptible calves each inoculated with 204 ml of blood pooled from 12 bison did not develop anaplasmosis. Results of this study indicate American bison have resistance to natural A. marginale infection.

Agglutination Tests

Health practice at the technologic/folk interface: witchcraft as a culture-specific diagnosis.

"Witchcraft illness" is a widespread belief among many people, even after acculturation to technological concepts of illness etiology. Two cases are presented to show that such beliefs can complicate physical or psychological dysfunctions, or themselves can be the primary origin of physical or psychological dysfunctions. In both instances, witchcraft beliefs take on a dynamic of their own and must be resolved both in terms of the patient's culture as well as the clinician's treatment plan. Considering such phenomena from the vantage point of family systems provides useful insights into etiology as well as amelioration. The latter requires engaging all parties in the health care system-clinician, patient, family, and indigenous health caretakers.

Adult

Problems of child health in a Peruvian shanty town.

The basic child-health problems in the shanty towns of Lima are protein-calorie malnutrition and infectious disease. The background of social, economic and cultural conditionsa are related to these main health problems. The basic problems are poverty, lack of sewage disposal and running water, and the maldistribution of public expenditure between city and countryside on one hand and curative and preventive medicine on the other. Despite official statistics, which show a steadily decreasing infant mortality rate in Peru, and all other Latin American countries, it seems that the Infant Mortality Rate is almost twice the official states rate. Health education, particularly in nutritional matters, is not adapted to indigenous foods and customs, but attempts to promote westernized conceptrs. Medical care in Peru is by large directed to the needs of the middle class, and the middle class by and large dictates the type of medical care available.

Child

A heroin "epidemic" in Asia.

Heroin "epidemics" have been reported in North America but not in Asia. Following passage of an anti-opium law in Laos, heroin use suddenly began in one area during 1972. Initially heroin use prevailed among indigenous Asian addicts, mostly older addicts who gradually switched from opium to heroin. In addition, there evolved a new group of indigenous addicts: young, single, unemployed males in urban areas whose first narcotic drug was heroin. After the appearance of heroin in Laos, increasing numbers of younger Americans and Europeans were soon attracted to heroin use in Laos.

Adolescent

Haemoglobins J in Canada.

A search has been conducted in Canada on 222,000 blood samples, for haemoglobin variants detectable electrophoretically. A pattern of Hbs A h was found in 41, and of these, 23 have been identified as J Baltimore (in 18), J Toronto (in 1), J. Broussais (in 3) and St. Claude (in 1). 12 instances of J Baltimore and one of J Toronto came from English Canadians, while the remainder came from French Canadians. Of those not identified, five were considered to be J-alpha and 13 J-beta variants. The known distribution and incidence of J Baltimore, and of the Hbs J that have been found in the indigenous populations of the United Kingdom and of France, are reviewed.

Canada