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Mapping the future of common diseases: lessons from psoriasis.

Psoriasis (OMIM*177900) is a common, chronic, hyperproliferative inflammatory disorder of the skin affecting approximately 2% of Caucasians. Despite the prevalence of psoriasis in general population, significant differences in the incidence among Japanese, Eskimos, West Africans, north American blacks and American natives are well known. The cause for these variations are likely to be both genetic and environmental. Independent genomewide scans have suggested the involvement of a large number of chromosomal regions (loci), but so far only poor susceptibility genes have been suggested. We discuss genetic basis of the disease, results and interpretations of relevant studies, with particular regard to study design and future perspectives. Indeed to date, mapping genes which contribute to complex diseases is one of the major challenge in the post-genomic era.

Adult↗

Clinical research in the Canadian North: an overview of a decade of participation in the McGill University-Baffin Zone Project.

Chronic otitis media and sensorineural hearing loss secondary to noise are major health problems today among the Canadian Inuit (Eskimo). The complexities of conducting clinical research in a region greater in surface area than all of Western Europe are significant. The problems imposed by logistics, weather, lack of continuity in administrative support and the cultural differences encountered and what has been achieved are reviewed.

Arctic Regions↗

Pneumatization of the temporal bones in a Greenlandic Inuit anthropological material.

The degree of pneumatization of the temporal bones correlates with exposure during childhood and adolescence to infectious middle ear diseases (IMED), both acute and chronic. The pneumatized area as seen on cranial X-rays can be measured. This was applied to an anthropological material in order to develop methods for assessing ancient populations' exposure to IMED. Fifty-six Greenlandic Inuit (Eskimo) crania were examined. The crania were sexed and measured. X-rays were taken bilaterally, using the projection of Runström II, and the pneumatized area was measured planimetrically by computer. In blind trials it was found that the inter- and intraobserver variation was non-significant; that the degree of pneumatization of the temporal ossa did not reflect cranial size or sexual dimorphism; and that the pneumatized areas correlated bilaterally. Asymmetry in the size of the pneumatized areas, an indicator of exposure to IMED, was found in 5 crania (9%).

Female↗

Epstein-Barr virus (EBV) infection and undifferentiated carcinoma of the parotid gland in Caucasian patients.

The Epstein-Barr virus (EBV) has been detected in certain types of lymphoma and some epithelial neoplasms such as nasopharyngeal lymphoepithelioma and occasional undifferentiated carcinomas in several organs including the salivary glands. However, clonal EBV genomes have been detected in undifferentiated carcinomas of the parotid gland exclusively in Alaskan natives and Eskimos, both groups being at the highest risk for nasopharyngeal carcinoma. The authors investigated the possibility that EBV may be present in undifferentiated parotid carcinomas in Caucasian subjects. To test this hypothesis, in situ hybridization (ISH) technique with biotinylated EBV-DNA probes was utilized on routinely processed, paraffin-embedded tissues from 7 cases of undifferentiated carcinomas of the parotid gland. EBV genomes were demonstrated in the cytoplasm of tumor cells from 3 out of 7 specimens tested. Surprisingly, EBV genomes were found in 3 out of 5 (60%) undifferentiated carcinomas that had developed in patients with a history of a long-persisting asymptomatic parotid mass, which had suddenly increased in size. Conversely, none of the undifferentiated carcinomas with continuous and rapid growth studied was found to be positive for EBV-DNA by ISH technique. Taken together, these data might suggest a possible role of EBV in the transformation of benign parotid gland lesions into malignant and aggressive undifferentiated carcinoma of the parotid gland, the so-called carcinoma expleomorphic adenoma.

Adult↗

Low and high risk coronary patients discriminated by blood platelet fatty acid composition.

The distribution of 11 long-chain fatty acids in platelet phospholipids were subjected to multivariate statistical analysis with groups of high and low risk coronary patients and controls. The alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) had significant explanatory power between the groups. As has been anticipated from studies in Eskimos, the EPA fraction was low in coronary patients. It was lower in high risk patients than in low risk patients, and lower in patients below rather than above, 60 years of age. Young high risk patients had 1.2 +/- 0.2% (Mean, SE) EPA against 1.8 +/- 0.2% in young controls, (p = 0.035). Old low risk patients had the highest EPA and also the highest DHA, 2.9 +/- 0.3% against 2.3 +/- 0.2% in controls. The ALA was low in low risk patients. Patients with low platelet EPA and high serum cholesterol should be included in trials with EPA rich diets.

Aged↗

Lymphoepithelial carcinoma of the submandibular gland--a case report.

A case of lymphoepithelial carcinoma occurring in the left submandibular salivary gland is presented. Histologic features of this rare malignancy are described in detail. This unusual carcinoma has been described frequently in Eskimos and is usually located in the parotid gland. The raised serum IgG to Epstein-Barr virus capsid antigen suggests a causal relationship between Epstein-Barr virus and this type of salivary gland carcinoma.

Adolescent↗

Diabetes among Alaska Natives: a review.

This review summarizes the published information on diabetes mellitus and gestational diabetes among Alaska Natives. The most recently published age-adjusted prevalence was 28.3/1000 in 1998. There is evidence of a steadily increasing prevalence, documented both by cross sectional screening studies and patient registry methods. The overall incidence rates in 1986-1998 of lower extremity amputation (6.1/1000) and renal replacement therapy (2.1/1000) appear to be lower than those in other Native American populations in the United States. Incidence of stroke and MI in 1986-1998 varied widely by ethnic group and gender with Eskimo women having the highest rate of stroke (19.6/1000), and Aleut men the highest rate of MI (14/1000). The overall mortality among diabetic Alaska Native people in 1986-1993 (43.2/1000) was somewhat lower than that in other US diabetic populations, with heart disease being the most common cause of death. A high rate of gestational diabetes (6.7%) was reported in one region in 1987-88, but this appeared to decline following nutritional education intervention. In screening studies, the prevalence of abnormal glucose tolerance has been found to be positively associated with body mass index and negatively associated with daily seal oil or salmon consumption and higher levels of physical activity. Observations on the prevalence and relationships among other factors in the insulin resistance syndrome are summarized. Suggestions for prevention of diabetes and further studies are presented.

Adult↗

Reduction of amputation rates among Alaska Natives with diabetes following the development of a high-risk foot program.

OBJECTIVE: The prevalence of diabetes is increasing rapidly among Alaska's Indian, Eskimo and Aleut populations. Approximately half the Native people with diabetes have no road access to hospitals or physicians, presenting a challenge in the attempt to prevent lower extremity amputation as a complication. In late 1998 funding became available for diabetes prevention and treatment among Native Americans. The tribal health corporations in Alaska decided to use a portion of this funding to implement a high-risk foot program to decrease the amputation rate. PROGRAM DESIGN: The program initially involved a surgical podiatrist who provided training to local staff and performed preventive and reconstructive surgery on several patients with impending amputations. The program then provided training for a physical therapist to become a certified pedorthist. This individual established the long-term maintenance phase of the program by conducting diabetic foot clinics routinely at the Alaska Native Medical Center, a referral center in Anchorage. He also travels to other regions of the state to provide training for village and hospital-based health care providers and to conduct field clinics. A system was established in a common database management program to track the patients' foot conditions. Patient education is emphasized. RESULTS: The overall amputation incidence among all Alaska Native patients with diabetes decreased from 7.6/1,000 in the pre-program period (1996 to 1998) to 2.7/1,000 in the post-program period (1999-2001) (p<.001). The rate among Aleuts, who previously had the highest amputation incidence, decreased from 17.4/1,000 to 3.1/1,000 over the same time periods (p<.001). Among people who had had diabetes at least 10 years, the overall amputation incidence decreased from 16.4/1,000 to 6.8/1,000 (p=.021); among Aleuts the rate fell from 24.5/1,000 to 2.6/1,000 (p=.01). CONCLUSIONS: Though longer follow-up is needed, these data suggest that even in populations living in isolated regions, diabetic amputations can be prevented by a coordinated system to identify high-risk feet and provide preventive treatment and education in the context of a comprehensive diabetes management program in an integrated health system.

Alaska↗

Breast cancer among Alaska Native women potentially exposed to environmental organochlorine chemicals.

OBJECTIVES: To determine if an increased rate of breast cancer in Alaska Native women is related to their consumption of a subsistence diet that may contain p,p'-dichlorodiphenylethylene (DDE) and polychlorinated biphenyls (PCBs). STUDY DESIGN: A retrospective case control design. METHODS: We analyzed banked serum collected between 1981 and 1987 from 126 Alaska Native women, including 63 case women who subsequently developed breast cancer and 63 age-matched control women who remained cancer-free. Serum was analyzed for DDT, DDE, 13 other chlorinated pesticides, and 28 PCB congeners. RESULTS: The geometric mean for p,p'-DDE levels among case women was 8.67 ppb (95% Confidence Interval 7.48, 10.04); among control women, the geometric mean was 7.36 ppb (6.53, 8.30). The geometric mean for total PCB levels among case women was 4.55 ppb (3.61, 5.74) and for control women, the geometric mean was 6.10 ppb (4.73, 7.86). Cancer status and total PCB levels varied across ethnicity (i.e., Eskimo, Aleut, and Indian) but DDE levels were uniform among these ethnic groups. Using conditional logistic regression analysis to adjust for potential confounders (e.g., ethnicity, family history of breast cancer, parity), we found an odds ratio of 1.43 (0.46, 4.47) for the highest tertile of DDE exposure and 0.42 (0.07, 2.38) for the highest tertile of total PCB exposure. CONCLUSIONS: Although the results are limited by small sample size and restricted risk factor information, our findings of higher DDE levels, but lower PCB levels among women with breast cancer are consistent with previous research. Our results confirm exposure to organochlorines among Alaska Native women but do not identify these exposures as a significant risk factor for breast cancer.

Alaska↗

Echinococcosis in Arizona and New Mexico. Survey of hospital records, 1969-1974.

In 1974, seven cases of human echinococcosis were diagnosed in Arizona and New Mexico. A retrospective survey of Arizona and New Mexico hospitals obtained data on ten additional cases reported for the 5-year period 1969 through 1973. Sixteen cases were diagnosed as Echinococcus granulosus infections and one as E. multilocularis infection. The latter infection was in an Eskimo from Alaska, where E. multilocularis is endemic. All of the 16 E. granulosus cases were probably acquired autochthonously; 14 were diagnosed in American Indians of the Navajo (8 cases), Zuni (4 cases), and Santo Domingo (2 cases) tribes; the remaining 2 cases were diagnosed in non-Indian women. This is the first published account of echinococcosis autochthonous to Arizona and New Mexico. Evidence suggests that the infection may have been introduced only relatively recently to the areas populated by the American Indians and that parasite transmission to humans is increasing.

Adolescent↗

Spontaneous death of Echinococcus multilocularis: cases diagnosed serologically (by Em2 ELISA) and clinical significance.

Nine cases of asymptomatic alveolar hydatid disease (AHD) of the liver were diagnosed in 1985 among Eskimos from the endemic region of western Alaska. The patients were identified by screening with the enzyme-linked immunosorbent assay, using purified Echinococcus multilocularis antigen (Em2 ELISA). Five patients, and one diagnosed earlier (1979), were found to have lesions in which the larval E. multilocularis had died spontaneously at an early stage of infection. Viability was assessed histologically; by the avidin-biotin immunohistochemical method; and in vivo through intraperitoneal inoculation of membranes of the larval cestode into red-backed voles, Clethrionomys rutilus. The results were in agreement with the clinical impression, based on findings by computerized tomography and ultrasound scanning, and on the macroscopic appearance of the lesions, that the cestode was dead. Spontaneous death of E. multilocularis in humans has not been previously reported. The findings show that the Em2 ELISA may be positive in patients having lesions of AHD in which the etiologic agent is no longer viable.

Aged↗

Risk factors for infection with Echinococcus multilocularis in Alaska.

We studied 19 Eskimo patients with alveolar hydatid disease from the north-western coast of Alaska for risk factors for infection with Echinococcus multilocularis. Each case-patient was matched by age and sex with 2 unrelated controls who had no clinical or serologic evidence of infection with E. multilocularis and who resided in three villages endemic for alveolar hydatid disease. Behaviors thought to increase exposure to E. multilocularis and the chronologic occurrence of these behaviors in the participant's life were assessed by a standardized questionnaire. Case-patients were more likely than controls to have owned dogs for their entire lives (odds ratio 6.00, P less than 0.05), tethered their dogs near the house (odds ratio 8.50, P less than 0.05), and lived in houses built directly on the tundra rather than on gravel or a permanent foundation (odds ratio 11.00, P less than 0.01). Case-patients were not more likely to have owned sled dogs, trapped or skinned foxes, or engaged in other outdoor activities away from home. These findings suggest that controlling the parasite in the domestic dog population, as well as controlling the dog population itself, are important aspects of preventing alveolar hydatid disease in the northwestern Native Alaskan population.

Adolescent↗

Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus.

BACKGROUND: Knowledge of the outcome of chronic hepatitis B virus (HBV) infection is limited. OBJECTIVE: To determine the incidence of and risk factors for adverse events (hepatocellular carcinoma and end-stage liver disease) and clearance of hepatitis B e antigen (HBeAg) and surface antigen (HBsAg) in carriers of HBV. DESIGN: Population-based cohort study of hepatitis B carriers who were observed for a median of 12.3 years as part of an active surveillance program to detect carriers with hepatocellular carcinoma. SETTING: 126 communities in Alaska. PATIENTS: 1536 Alaska Natives with chronic hepatitis B. MEASUREMENTS: Bivariate comparisons, multivariable models, and other statistical methods were used to examine the relationships of risk factors to outcomes and clearance of HBeAg and HBsAg. RESULTS: 1536 chronic HBV carriers were followed up for 19 430 person-years from their first HBsAg-positive test result. At the first serologic test, 641 were HBeAg positive and 893 were anti-HBe positive. Older carriers were more likely than younger carriers to clear HBeAg (P < 0.001). The observed probability of clearing HBeAg within 10 years of diagnosis was 72.5%. Clearance of HBsAg occurred in 106 (7%) of all carriers and was positively associated with older age and positive result on initial anti-HBe test. The incidence of adverse events was 2.3 per 1000 carrier-years, and the incidence of hepatocellular carcinoma was 1.9 per 1000 carrier-years (2.3 in men and 1.2 in women). Risk for hepatocellular carcinoma increased with age, among those of Yupik Eskimo ethnicity, and among carriers who reverted from anti-HBe to HBeAg. CONCLUSION: In HBsAg-positive carriers, observed clearance of HBeAg was more than 70% during the first 10 years of follow-up.

Adolescent↗

Os trigonum. Variation of a common accessory ossicle of the talus.

The authors present a pictorial essay showing the range of variability of separate and attached os trigona in dry-bone specimens. The presence of free os trigona is found to be 1.7% in an early 20th-century skeletal sample, with no findings of the trait in 513 tali of prehistoric native Americans and Eskimos.

Adult↗

Viral serologic survey of bowhead whales in Alaska.

Serum samples from 21 of 36 Eskimo harvested bowhead whales (Balaena mysticetus) were positive by virus neutralization (50% endpoint titer > or = 1:28 and/or 100% endpoint titer > or = 1:20) for antibodies to at least one virus serotype from the calicivirus family, vesicular exanthema of swine virus (VESV) and San Miguel sea lion virus (SMSV). Many animals were positive to more than one serotype when using the Spearman-Karber (S-K) method for calculating antibody titers. The most common serotype detected was VESV F55 with 6 of 36 (17%) by the Monto and Bryan (MB) titer calculation method, and 17 of 36 (47%) by the S-K titer calculation method. Vesicular exanthema of swine virus 1934B antibody was detected in 3 of 36 (8%) and 5 of 36 (14%) whales using the MB and S-K methods, respectively. Vesicular exanthema of swine virus J56 antibody was detected in 3 of 36 (8%) by the S-K method only. All whales < 8.5 m (estimated yearlings, n = 6) were seronegative for VESV J56 and 1934B while 10% and 17% of the whales > 8.5 m were positive, respectively. Whales assumed to be sexually mature (> 13 m) had a higher prevalence of antibody to VESV 1934B and SMSV 8 than those < 13 m. Gender had an effect on seroprevalence of antibody to VESV 1934B as titers > or = 1:28 (S-K method) occurred in 18% of the females and 7% of the males. Antibody to other serotypes (SMSV 8 and 12) occurred less frequently (< 6%) at an antibody titer > or = 1:28 by the S-K method. All 36 whale sera were negative for antibody to VESV-A48, B51, C52, D53, E54, G55, H54, I55, and K54; Tillamook calicivirus, and dolphin morbillivirus; and SMSV-1, 2, 4, 5, 6, 7, 9, 10, 11, and 13 by the S-K method.

Alaska↗

Stature, sitting height and relative sitting height of female northern Kyushuites.

Stature, sitting height and relative sitting height (a ratio of sitting height to stature) of 318 high school girls of 17 years of age in Kitakyushu City were studied. They consisted of groups over a three-year period; 1973, 1980 and 1984. There are statistically no significant changes in the stature, in the sitting height, and in the relative sitting height among these three groups. The relative sitting height of these three groups is about 54%, which is about the same as among the Chinese, Eskimos, American-Indians and the Hokkaido-Ainu.

Adolescent↗

Flushing response and its role in alcohol disease in Siberian populations.

The characteristics of alcohol-induced flushing response were studied in some Siberian Native populations (Chukchi, Eskimo, Jakuts, Udege, and Nanaian). Flushing peculiarities were estimated and the interrelationship with drinking patterns, the ethanol patch test (EPT), and somatic disorders were analyzed. Frequency of flushing response varied from 9.0% to 66.7%, and was more often apparent among females. Only the Nanaian demonstrated typical flushing, which did not allow them to consume high doses of alcohol. In the rest of the populations flushing was "atypical," i.e., appearing sometimes after high doses of alcohol but not interrupting alcohol drinking, and not associated with a positive EPT. Direct genotyping in DNA samples of Chukotka Natives did not reveal atypical allele aldehyde dehydrogenase (AIDH 2/2). Frequencies of alcohol problems, alcohol dependence symptoms, and somatic disorders (arterial hypertension, silent ischemia, diffuse liver lesions, and noncalculous cholecystitis) were higher among atypical flushers compared to nonflushers (p < 0.05-0.01). The mechanism of the observed atypical flushing response is unknown. We speculate on its hereditary nature, since flushing alcoholics, compared to nonflushers, reported that their parents had flushing responses significantly more often. Further studies are required.

Adolescent↗