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PubMed1999

Neuroepidemiologic research initiatives on Guam: past and present.

Since the middle of this century, a remarkable concentration of cases of neurodegenerative disease(s), referred to as amyotrophic lateral sclerosis and Parkinson-dementia complex (ALS/PDC), has been recognized among Chamorro natives of Guam. Intense investigations over the last 4 decades have failed to determine the etiology of these invariably fatal diseases. Over the same time period, the incidence of ALS has decreased dramatically, the incidence of PDC has decreased, but to a lesser degree, and age at onset has shifted to a later age by about 1 decade. Almost 50% of demented patients present without the classical Parkinsonian features of PDC, and the morphological picture has changed. Results of past and present research initiatives are reviewed.

Amyotrophic Lateral Sclerosis↗
PubMedDate not supplied

Rare neuropil threads in amyotrophic lateral sclerosis and parkinsonism-dementia on Guam and in the Kii Peninsula of Japan.

Using three different silver impregnation methods and antisera against microtubule-associated protein-tau (MAP-tau) and amyloid beta/A4 protein, we demonstrated abundant neurofibrillary tangles (NFTs), rare senile plaques, absence of amyloid angiopathy and rare MAP-tau- and silver-positive neuropil threads in the hippocampus of patients with amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) on Guam and in the Kii Peninsula of Japan. In contrast, abundant neuropil threads, NFTs, senile plaques with associated dystrophic neurites and amyloid angiopathy were confirmed in Alzheimer disease patients. These observations indicate that there may be important factor(s) responsible for the difference in the deposition and distribution of amyloid beta/A4 protein and MAP-tau between Pacific ALS and PD and Alzheimer disease.

Aged↗
PubMed1983

Further studies on the genetics of the Chamorros of Guam: dermatoglyphics.

The present study represents a continuation of our efforts to further define the genetic structure of the Chamorro population of Guam. The dermatoglyphic features of Guamanian Chamorros differ significantly from those of Western Carolinians from the Outer Islands of Yap in fingerprint patterns, model types of C line, frequency of patterns in the thenar/I area and in the presence of Sydney creases. The results of this analysis confirm earlier data from serological and other genetic markers that Guamanian Chamorros are genetically more closely related to the people of southeastern Asia than to their Micronesian neighbors to the south.

Adult↗
PubMedDate not supplied

Immunohistochemical study of the hippocampus in parkinsonism-dementia complex on Guam.

This investigation concerns the expression of paired helical filaments, tau protein, ubiquitin, beta-amyloid protein, and synaptophysin in the hippocampus of patients with parkinsonism-dementia complex on Guam (PDC) and Alzheimer's disease. Alzheimer's neurofibrillary tangles (NFTs) were identified in all cases of PDC and Alzheimer's disease by the modified Bielschowsky method, with which they were readily detected, and by immunohistochemical procedures using antibodies to paired helical filaments, tau protein, and ubiquitin. Observations regarding the different morphological stages indicated that NFTs were similar in PDC and Alzheimer's disease. The same markers were also useful for detecting neuropil threads, abundant in the CA1 field and the subiculum in both diseases. In the CA4 region of some PDC cases, prominent threads were noted. No senile plaques or amyloid angiopathies were seen in the hippocampus of the PDC cases examined. There was a significant decrease in synaptophysin immunoreactivity, most pronounced in the subfield CA1 and the subiculum, as well as in the outer molecular layer of the dentate gyrus, in both disorders.

Alzheimer Disease↗
PubMed1991

Observations on the ecology of Salmonella waycross and Salmonella typhimurium on Guam.

A period of high incidence of human Salmonella infections on the island of Guam saw the emergence of S. waycross as the most commonly isolated serotype as well as a concurrent decreasing proportion of isolates due to S. typhimurium. Predation of local rodents by an introduced snake is believed to account for the decreased prevalence of S. typhimurium infections, but reasons for the increased prevalence of S. waycross infections are unknown.

Animals↗
PubMed1995

The health status and characteristics of hypertensives in Guam.

Studies of Asian Pacific American populations are often flawed because while the population is quite heterogeneous, researchers usually collapse them into a single category, making it impossible to assess the health status or needs of individual Asian Pacific American ethnic groups. Using a probability sample of Guam residents, the analysis reported here addresses the problem by documenting the health status and characteristics of Chamorro and Filipino hypertensives. In contrast to predictions from the literature, Chamorros have a higher prevalence of hypertension than Filipinos. Additional results show that hypertensive Chamorro men and women are from lower socioeconomic status levels than their Filipino counterparts, while hypertensive men and women of both ethnic groups appear equally likely to be overweight and to suffer diabetes. Male hypertensives are at greater risk for psychological distress than normotensives, and have a greater chance of heart failure. Compared to Filipinos, hypertensive Chamorros are more likely to evaluate their overall physical health as poor.

Adult↗
PubMed1985

Disappearance of high-incidence amyotrophic lateral sclerosis and parkinsonism-dementia on Guam.

The high incidence rates of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) occurring among the Chamorros of Guam have declined to rates only slightly higher than those observed in the continental United States. This decline has occurred principally among males, especially those born after 1920 and living in areas where calcium and magnesium levels are low in soil and water. The male-to-female ratio among affected patients now approaches unity, compared with ratios of 2 to 1 for ALS and 3 to 1 for PD three decades ago. These changes are consistent with the hypothesis that the previously high incidence resulted from defects in mineral metabolism and secondary hyperparathyroidism, provoked by nutritional deficiencies of calcium and magnesium, with resultant deposition of calcium and aluminum in neurons.

Adult↗
PubMed1992

Content of the neurotoxins cycasin (methylazoxymethanol beta-D-glucoside) and BMAA (beta-N-methylamino-L-alanine) in cycad flour prepared by Guam Chamorros.

Exposure to cycad seed kernel is an etiologic factor for the western Pacific amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC). Traditionally processed cycad flours (n = 17) obtained from Chamorro residents of Guam and the adjacent island of Rota at risk for neurodegenerative disease were extracted and analyzed by high-performance liquid chromatography for content of beta-N-methylamino-L-alanine (BMAA) and methyl-azoxymethanol beta-D-glucoside (cycasin). Cycasin (detection limit: picomole) was present in concentrations of 0.004 to 75.93 micrograms/g (mean, 12.45 +/- 5.0 micrograms/g), and levels of BMAA (detection limit: subpicomole) ranged from 0.00 to 18.39 micrograms/g (mean, 5.44 +/- 1.56 micrograms/g). On average, cycasin content was approximately 10 times higher than that of BMAA. The largest concentrations of cycasin were found in samples from villages with a high reported prevalence of ALS/PDC. Ingestion of cycad-derived food would result in estimated human exposure to milligram amounts of cycasin per day. The cytotoxic properties of cycasin merit consideration in relation to the etiology of western Pacific ALS/PDC.

Amino Acids, Diamino↗
PubMed1997

Familial nature and continuing morbidity of the amyotrophic lateral sclerosis-parkinsonism dementia complex of Guam.

Chamorros suffer from two neurologic syndromes known as ALS and the parkinsonism-dementia complex (PDC) of Guam. We report mortality figures for these syndromes during 1991 to 1995 and compare them with those at 5-year intervals dating back to 1951. In contrast to predictions of disease disappearance, both syndromes remain prevalent. However, age of onset and age at death have increased for both syndromes, suggesting that shifting environmental factors are causing disease postponement. We also report the clinical, familial, neuropathologic, and immunohistochemical findings on a consecutive autopsy series of Guamanian Chamorro cases. Twelve cases were diagnosed as PDC, known locally as "bodig," and three as ALS, known locally as "lytico." All but three of these fifteen patients had a pronounced family history of similar illness. Eight of twelve boding patients had siblings who were also affected with bodig; two of three lytico cases had siblings afflicted with lytico. The family histories are compatible with genetic transmission of each syndrome. The neuropathology of bodig is characterized by severe and widespread neurofibrillary tangle (NFT) development. NFTs are surrounded by reactive microglia and reactive astrocytes, and complement proteins and other molecules connected with inflammation are associated with them. Similar inflammatory responses also occur in Alzheimer's disease (AD) but have been largely attributed to the presence of senile plaques. These data indicate that tangles, as well as plaques, generate inflammatory reactions that such reactions may exacerbate the fundamental pathology in bodig as well as in AD.

Aged↗
PubMed2002

ALS and PDC of Guam: forty-year follow-up.

BACKGROUND: It was noticed in the mid-1950s that the incidence of ALS and parkinsonism--dementia complex (PDC) were much higher on Guam than anywhere else in the world. In 1958, a registry of patients and controls was established to ascertain the familial and genetic aspects of these diseases. Patients and individually matched controls and their relatives were registered from 1958 to 1963. The registry was updated and analyzed in 1998 through 1999. OBJECTIVE: To ascertain whether first-degree relatives of patients had a higher risk for developing ALS or PDC than relatives of controls. METHODS: During the period of 1958 to 1963, 126 new patients and 126 individually matched controls and their respective first-degree relatives and spouses were evaluated neurologically and registered. Forty years later, the number of new cases among the patient and control relatives were compared to an expected number of new cases based on the age- and sex-specific incidence of ALS and PDC in the population at large. RESULTS: From 1958 to 1999, there were 102 new ALS or PDC cases among relatives of patients and 33 among relatives of controls. These values were compared with the derived expected values. There were more observed than expected new cases among patients' relatives, and less observed cases than expected among the controls' relatives. CONCLUSIONS: Relatives of patients with ALS or PDC have significantly higher risks for developing the disease than the Guamanian population, whereas relatives of controls have significantly lower risks.

Aged↗
PubMed2002

Cycad neurotoxins, consumption of flying foxes, and ALS-PDC disease in Guam.

The Chamorro people of Guam have been afflicted with a complex of neurodegenerative diseases (now known as ALS-PDC) with similarities to ALS, AD, and PD at a far higher rate than other populations throughout the world. Chamorro consumption of flying foxes may have generated sufficiently high cumulative doses of plant neurotoxins to result in ALS-PDC neuropathologies, since the flying foxes forage on neurotoxic cycad seeds.

Alzheimer Disease↗
PubMed1994

The influence of ethnicity and socioeconomic status on the use of mammography by Asian and Pacific island women on Guam.

The effects of ethnicity and socioeconomic status on the use of screening mammograms were assessed for a probability sample of Chamorro, Filipino, White, and other Asian and Pacific island women residing on Guam. Using logistic regression analysis, we found that socioeconomic status significantly influenced the use of screening mammograms among Chamorro and Filipino women while strong ethnic effects remained for other Asian and Pacific island women. Age had a significant influence of the use of screening mammograms. Marital status and having a young child in the home were not significant predictor variables.

Adult↗
PubMed2003

Concentrations of Cd, Co, Cu, Fe, Mn, Rb, V, and Zn in formalin-fixed brain tissue in amyotrophic lateral sclerosis and Parkinsonism-dementia complex of Guam determined by High-resolution ICP-MS.

Amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) are neurodegenerative disorders that occurred with extremely high frequency among the native population on Guam, especially in the 1950s and 1960s, but have substantially declined over the last half-century. The etiology of these diseases is unknown, but the most plausible hypothesis centers on imbalances in essential and toxic metals. We have determined the concentrations of Cd, Co, Cu, Fe, Mn, Rb, V, and Zn in formalin-fixed brain tissue collected during the period 1979-1983 from eight Guamanian patients with ALS, four with PDC, and five control subjects using high-resolution inductively coupled plasma-mass spectrometry. The concentrations of Cd are markedly and significantly elevated both in gray and white matter in ALS, but not in PDC patients. The concentrations of Zn are elevated for both patient groups, in both gray and white matter, but only the difference in gray matter for PDC is significant. For the other metals, no significant differences are found.

Adult↗
PubMed1992

Amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam: immunohistochemical studies.

The incidence of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) among the Chamorros in Guam is remarkably high. The patients with ALS have clinical and pathological characteristics similar to those in other parts of the world. The PDC patients display parkinsonism and progressive dementia and show a characteristic neuronal loss in certain parts of the central nervous system such as the hippocampus and substantia nigra. The Guamanian patients with ALS and PDC commonly have widespread Alzheimer's neurofibrillary changes, but without the associated senile plaques. We have applied immunohistochemical procedures to examine the expression of marker substances in Guamanian ALS and PDC. The markers studied include tau protein, ubiquitin, beta proteins, synaptophysin, calcineurin, Met-enkephalin, substance P and tyrosine hydroxylase. The results were compared with the findings in patients with Alzheimer's disease, Parkinson's disease, sporadic ALS and familial ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2000

The pediatric critical care experience at Naval Hospital Guam: suggestions for critical care training during residency.

OBJECTIVES: To determine the critical care experience encountered by three recently graduated military pediatricians at an overseas military hospital and present one model of maximizing allowable critical care training time during residency. METHOD: Retrospective reviews of all admissions to the special care nursery and intensive care unit at U.S. Naval Hospital Guam were performed for a 3-year and a 2-year period, respectively. Age, diagnosis, birth weight (if applicable), level of nursery care, invasive procedures performed in the nursery (endotracheal tube, umbilical artery, and umbilical venous catheter placement), patient outcome, and the need for medical transport were recorded. RESULTS: During a 3-year period, there were 122 admissions to the special care nursery (7.1% of all deliveries). In addition, pediatricians performed a total of 53 invasive procedures on these patients, and 29 infants required medical transport to an off-island neonatal intensive care unit for additional care. During a 2-year period, 70 pediatric patients were admitted to the adult intensive care unit, representing 10.2% of all intensive care unit admissions during this period. Fourteen of these patients required medical transport to an off-island referral hospital. CONCLUSION: Graduating military pediatric residents may be faced with caring for a wide range of critically ill neonatal and pediatric patients depending on their assignment. Residency training programs, with the recent increased emphasis on primary pediatric care, will need to streamline instruction in pediatric critical care to provide maximal benefit to the resident while maintaining compliance with Residency Review Committee guidelines.

Adolescent↗
PubMed1984

Effects of the 1918 influenza pandemic mortality experience on subsequent fertility of the native population of Guam.

An analysis of the effects of the influenza epidemic that occurred in Guam in 1918 is presented. "A sample of records for 321 individuals who died during this peak epidemic period and for whom complete linked family records have been compiled was analyzed to study the effects of this mortality on subsequent fertility and population growth patterns." The results suggest that the long-term demographic effect of the epidemic on the native population was minimal.

Cause of Death↗
PubMed2002

A leptospirosis outbreak on Guam associated with an athletic event.

Following an "extreme-adventure" athletic event on the island of Guam, 21 of 105 participants reported being ill. Three of 10 participants who reporting having a fever (temp > 101EF) had laboratory confirmed leptospirosis. An analysis of risk factors reported by both ill and not-ill race participants suggested that exposure to recreational waters was responsible for these infections.

Community-Acquired Infections↗
PubMed2002

Living the health transition among the Chamorros of Guam.

Health transition in the Pacific islands reflects the richness of diversity created by varied socio-cultural, ecological, and politico-economic systems and, therefore, requires the inclusion of the local cultural context in health assessment, planning, and program development. This paper focuses on the health transition of the Chamorros of Guam, blending assessment of health trends with the cultural contexts associated with them. The review of health trends reveals that the Chamorros are experiencing a mixed transition, including a combination of infectious and chronic diseases, in addition to the increasing impact of health risk behaviors, which have led to increasing rates of injury-related mortality. The cultural review presents Chamorro perceptions and values in their extended, multigenerational family system, in traditions of caring and sharing within their communities, and in the continued use of their traditional healers. By paying attention to the Chamorro's cultural perspectives and concerns, a "window" is provided to understand the interaction of changing population trends with their actual lives as well as an opportunity to integrate culture and health in our understanding of the health transition.

Adolescent↗