An elderly man with gastric cancer, Saint's triad and Heyde's syndrome.

This case study describes a 71-year-old man with signet-ring cell gastric adenocarcinoma and malignant sigmoidal polyp; and typical features of Saint's triad and Heyde syndrome. He had digestive bleeding, two types of hernia, diverticulosis, arterial hypertension, malignant polyp, and antecedent of smoking, lung tuberculosis, and surgical correction of aortic valve stenosis. There is a hypothetical inverse relationship between herniosis and development of malignancy; however, the patient herein described presented gastric and sigmoidal cancers. Gastrointestinal malignancies are sometimes associated with paraneoplastic entities, isolated or manifested as syndromes, but neither Saint's triad or Heyde syndrome have been included. This patient persisted clinically stable during the preoperative period, but suddenly died; Trousseau's syndrome would be the most probable mechanism of sudden death in this setting. Case reports can stimulate further studies to get additional knowledge about unusual entities.

An elderly man with gastric cancer, Saint's triad and Heyde's syndrome / Un anciano con cáncer gástrico, tríada de Saint y síndrome de Heyde

This case study describes a 71-year-old man with signet-ring cell gastric adenocarcinoma and malignant sigmoidal polyp; and typical features of Saint's triad and Heyde syndrome. He had digestive bleeding, two types of hernia, diverticulosis, arterial hypertension, malignant polyp, and antecedent of smoking, lung tuberculosis, and surgical correction of aortic valve stenosis. There is a hypothetical inverse relationship between herniosis and development of malignancy; however, the patient herein described presented gastric and sigmoidal cancers. Gastrointestinal malignancies are sometimes associated with paraneoplastic entities, isolated or manifested as syndromes, but neither Saint's triad or Heyde syndrome have been included. This patient persisted clinically stable during the preoperative period, but suddenly died; Trousseau's syndrome would be the most probable mechanism of sudden death in this setting. Case reports can stimulate further studies to get additional knowledge about unusual entities.

Este estudio de caso describe un hombre de 71 años de edad, con adenocarcinoma gástrico con células en anillo de sello y un pólipo maligno sigmoideo; y características típicas de la tríada de Saint y del síndrome de Heyde. Tuvo una hemorragia digestiva, dos tipos de hernias, divertículos, hipertensión arterial, y pólipo maligno; con antecedente de tabaquismo, tuberculosis pulmonar, y corrección quirúrgica de estenosis de la válvula aórtica. Hay una hipotética relación inversa entre hernioses y el desarrollo de malignidades; sin embargo, el paciente que se describe en el presente documento presentó cánceres gástrico y sigmoideo. Neoplasias gastrointestinales se asocian a veces con entidades para neoplásicas aisladas o manifiestan síndromes, pero ni la tríada de Saint ni el síndrome de Heyde se ha incluido. Este paciente persistió clínicamente estable durante el período preoperatorio, pero de repente murió; síndrome de Trousseau sería el mecanismo más probable de muerte súbita en esta situación. Los informes de casos pueden estimular más estudios para obtener un conocimiento adicional sobre esas entidades inusuales.

"DAK", a traditional decoction in Palau, as adjuvant for patients with insufficient control of diabetes mellitus type II.

ETHNOPHARMACOLOGICAL RELEVANCE: Can a medicinal plant be useful when standard modern treatment is insufficient? After a population survey in the Republic of Palau (retrospective treatment-outcome study, following the reverse pharmacology approach) on local treatments and associated outcomes for diabetes, a traditional drink made with Phaleria nisidai Kaneh and several other plants called "Delal A Kar", (meaning "mother of medicine") appeared as a promising therapy. This is the first clinical study on a standardized version of "Delal A Kar" called DAK. AIMS/HYPOTHESIS: This is a study of the effect of DAK as adjuvant therapy when diabetes control is insufficient. METHODS: In this randomized, double blind, crossover study conducted in Koror, Palau, DAK or placebo was assigned to 68 patients with type II diabetes treated with oral hypoglycemic agents and with insufficient glycaemic control. All patients received instructions on how to improve their diet and a home glucometer for blood glucose follow-up. RESULTS: Fifty-five patients completed the study and significant improvements were observed in both groups over the 12 weeks follow-up period: weight decreased an average of 2 to -4.5 pounds (p<0,001) and HbA1C also decreased from 9.7% to 7.8% (p<0,001), with a consistent trend toward better outcomes after DAK, as compared to placebo. The average effect of Ongael was 0.5% (SD 2.5) decrease of HbA1C. Furthermore, seventy-five percent (41/55) of the patients reduced their HbA1C by at least 0.7% at 12 weeks. CONCLUSION: The observed trends in this trial suggest that poorly controlled diabetic patients improved their control of diabetes within 12 weeks when drinking DAK for at least 6 weeks. The drink DAK, in addition to the usual prevention activities of special diet and physical exercise, was followed by improvement of diabetes control (HbA1C) and decrease of blood pressure and weight. TRIAL REGISTRATION: The study protocol was approved by the Institutional Ethical Committee and registered by international Australia and New Zealand trial registry (Request Number: 369395) FUNDING: Pacific Academic Institute for Research office fund, Belau Medical Clinic, The Environment, Inc, Antenna Foundation, Grandjean and Michèle Berset funds and the Weil Foundation.

Analysis of Shared Haplotypes amongst Palauans Maps Loci for Psychotic Disorders to 4q28 and 5q23-q31.

To localize genetic variation affecting risk for psychotic disorders in the population of Palau, we genotyped DNA samples from 203 Palauan individuals diagnosed with psychotic disorders, broadly defined, and 125 control subjects using a genome-wide single nucleotide polymorphism array. Palau has unique features advantageous for this study: due to its population history, Palauans are substantially interrelated; affected individuals often, but not always, cluster in families; and we have essentially complete ascertainment of affected individuals. To localize risk variants to genomic regions, we evaluated long-shared haplotypes, ≥10 Mb, identifying clusters of affected individuals who share such haplotypes. This extensive sharing, typically identical by descent, was significantly greater in cases than population controls, even after controlling for relatedness. Several regions of the genome exhibited substantial excess of shared haplotypes for affected individuals, including 3p21, 3p12, 4q28, and 5q23-q31. Two of these regions, 4q28 and 5q23-q31, showed significant linkage by traditional LOD score analysis and could harbor variants of more sizeable risk for psychosis or a multiplicity of risk variants. The pattern of haplotype sharing in 4q28 highlights PCDH10, encoding a cadherin-related neuronal receptor, as possibly involved in risk.

Yellow nail syndrome, Phrygian cap gallbladder and Saint's triad? Case report / ¿Síndrome de uñas amarillas, vesícula biliar en gorro frigio y tríada de Saint? Reporte de caso

The yellow nail syndrome is scarcely described and is characterized by dystrophic nails, pulmonary disturbances and lymphedema of extremities. A case of this syndrome is reported in an 89-year-old Brazilian woman with well-controlled diabetes mellitus and arterial hypertension. Additionally to the typical syndrome, the patient also presented pincer nails and yellow-brownish chromonychia. She was admitted because of acute abdominal symptoms associated with sigmoid diverticulitis and an adjacent abscess. The imaging studies revealed pulmonary and pleural changes, in addition to pericardial effusion. Incidentally, the features of Phrygian cap gallbladder anomaly were found. Neither diverticular disease nor gallbladder disorders have been related to yellow nail syndrome. In the present case study, the synchronism between some of these conditions could be casual; but diverticular disease, cholelithiasis, and diaphragmatic hernia are associated in the Saint's triad. MÉD UIS. 2015;28(3):387-91.

El síndrome de las uñas amarillas está poco descrito y se caracteriza por uñas distróficas, trastornos pulmonares y linfedema de las extremidades. Se presenta un caso de este síndrome en una mujer brasileña de 89 años de edad con diabetes mellitus bien controlada e hipertensión arterial. Adicionalmente al síndrome típico, la paciente presentó uñas en pinza y cromoniquia amarillo-marrón. La paciente fue admitida debido a síntomas abdominales agudos asociados con diverticulitis del sigmoide y un absceso adyacente. Los estudios de imágenes revelaron cambios pulmonares y pleurales, además de un derrame pericárdico. Incidentalmente, se encontraron anomalías características de vesícula biliar en gorro frigio. Ni la enfermedad diverticular ni los trastornos de la vesícula biliar se han relacionado con el síndrome de las uñas amarillas. En el presente estudio de caso, el sincronismo entre algunas de estas condiciones podría ser casual, pero la enfermedad diverticular, colelitiasis, y hernia hiatal se asocian a esta tríada. MÉD UIS. 2015;28(3):387-91.

Traditional local medicines in the republic of Palau and non-communicable diseases (NCD), signs of effectiveness.

ETHNOPHARMACOLOGICAL RELEVANCE: The aim of this survey was to describe which traditional medicines (TM) are most commonly used for non-communicable diseases (NCD - diabetes, hypertension related to excess weight and obesity) in Pacific islands and with what perceived effectiveness. NCD, especially prevalent in the Pacific, have been subject to many public health interventions, often with rather disappointing results. Innovative interventions are required; one hypothesis is that some local, traditional approaches may have been overlooked. MATERIALS AND METHODS: The method used was a retrospective treatment-outcome study in a nation-wide representative sample of the adult population (about 15,000 individuals) of the Republic of Palau, an archipelago of Micronesia. RESULTS: From 188 respondents (61% female, age 16-87, median 48,), 30 different plants were used, mostly self-prepared (69%), or from a traditional healer (18%). For excess weight, when comparing the two most frequent plants, Morinda citrifolia L. was associated with more adequate outcome than Phaleria nishidae Kaneh. (P=0.05). In case of diabetes, when comparing Phaleria nishidae (=Phaleria nisidai) and Morinda citrifolia, the former was statistically more often associated with the reported outcome "lower blood sugar" (P=0.01). CONCLUSIONS: Statistical association between a plant used and reported outcome is not a proof of effectiveness or safety, but it can help select plants of interest for further studies, e.g. through a reverse pharmacology process, in search of local products which may have a positive impact on population health.

Characterizing runs of homozygosity and their impact on risk for psychosis in a population isolate.

An increased abundance of runs of homozygosity (ROH) has been associated with risk for various diseases, including schizophrenia. Here we investigate the characteristics of ROH in Palau, an Oceanic population, evaluating whether these characteristics are related to risk for psychotic disorders and the nature of this association. To accomplish these aims we evaluate a sample of 203 cases with schizophrenia and related psychotic disorders-representing almost complete ascertainment of affected individuals in the population-and contrast their ROH to that of 125 subjects chosen to function as controls. While Palauan diagnosed with psychotic disorders tend to have slightly more ROH regions than controls, the distinguishing features are that they have longer ROH regions, greater total length of ROH, and their ROH tends to co-occur more often at the same locus. The nature of the sample allows us to investigate whether rare, highly penetrant recessive variants generate such case-control differences in ROH. Neither rare, highly penetrant recessive variants nor individual common variants of large effect account for a substantial proportion of risk for psychosis in Palau. These results suggest a more nuanced model for risk is required to explain patterns of ROH for this population.

Persistence of long-term immunity to hepatitis B among adolescents immunized at birth.

The long-term duration of recombinant hepatitis B vaccine-induced immunity among persons vaccinated starting at birth is still not well understood. Waning of vaccine-induced immunity could leave young adults at risk of hepatitis B virus infection due to behavioral or occupational exposures. We followed a cohort of children immunized starting at birth with a 3-dose regimen of recombinant hepatitis B vaccine (5 mcg, 2.5 mcg, 2.5 mcg). They were challenged with a booster dose of the hepatitis B vaccine 10 and 15 years after vaccination to assess anamnestic response as a measure of persistence of protection. Among 108 participants who had lost protective antibody levels against hepatitis B, the majority (>70%) had an anamnestic response to the booster dose; response rates did not decline significantly between 10 and 15 years follow-up periods. A high antibody concentration following primary vaccination was independently associated with an anamnestic response later on in life. Nonetheless, ~20-30% of participants were unable to mount an immune response after boosting. Hepatitis B revaccination might be required for persons vaccinated starting at birth if opportunities for hepatitis B virus exposure exist. Future vaccine recommendations should be based on studies ascertaining protection against clinically significant disease.

Copy number variants for schizophrenia and related psychotic disorders in Oceanic Palau: risk and transmission in extended pedigrees.

BACKGROUND: We report on copy number variants (CNVs) found in Palauan subjects ascertained for schizophrenia and related psychotic disorders in extended pedigrees in Palau. We compare CNVs found in this Oceanic population with those seen in other samples, typically of European ancestry. Assessing CNVs in Palauan extended pedigrees yields insight into the evolution of risk CNVs, such as how they arise, are transmitted, and are lost from populations by stochastic or selective processes, none of which are easily measured from case-control samples. METHODS: DNA samples from 197 subjects affected with schizophrenia and related psychotic disorders, 185 of their relatives, and 159 control subjects were successfully characterized for CNVs using Affymetrix Genomewide Human SNP Array 5.0. RESULTS: Copy number variants thought to be associated with risk for schizophrenia and related disorders also occur in affected individuals in Palau, specifically 15q11.2 and 1q21.1 deletions, partial duplication of IL1RAPL1 (Xp21.3), and chromosome X duplications (Klinefelter's syndrome). Partial duplication within A2BP1 appears to convey an eightfold increased risk in male subjects (95% confidence interval, .8-84.4) but not female subjects (odds ratio = .4, 95% confidence interval, .03-4.9). Affected-only linkage analysis using this variant yields a logarithm of the odds score of 3.5. CONCLUSIONS: This study reveals CNVs that confer risk to schizophrenia and related psychotic disorders in Palau, most of which have been previously observed in samples of European ancestry. Only a few of these CNVs show evidence that they have existed for many generations, consistent with risk variants diminishing reproductive success.

Recurrence risk to offspring in extended multiplex schizophrenia pedigrees from a Pacific Island isolate.

Genetic transmission plays a major role in the pathogenesis of schizophrenia. Family, twin, and adoption studies have consistently shown that risks in relatives are many times greater than the general population risk of approximately 1%. McGue, Gottesman, and Rao (1983; Am J Hum Genet 35:1161-1178) calculated risk estimates of 12.8% for offspring and 3.5% for nieces/nephews of schizophrenia patients based on a large data set of Western European families. The present study evaluated corresponding risk levels in Palau, an isolated population in Micronesia where the prevalence of narrowly (broadly) defined schizophrenia is 1.99% (2.67%) and cases cluster in extended pedigrees, 20 of which contain 80% of affected individuals. We hypothesized that offspring in these extended families would have a higher risk for schizophrenia than offspring in smaller schizophrenia pedigrees from more genetically heterogeneous populations. RDC diagnostic data based on complete ascertainment of cases and their families covering the past two generations were used to quantify empirical recurrence risks in the offspring and nieces/nephews of Palauan schizophrenia patients. Risks to 1st- and 2nd-degree offspring were approximately double the rates found in the smaller Western European families: 23.4% in the offspring of an affected parent, 6.4% in offspring with one affected aunt/uncle, and 15.0% in offspring with two or more affected aunts/uncles. Recurrence rates in offspring of an affected parent were 1.6 times higher in males (27.9%) than in females (17.7%). The high risk levels we found in Palauan offspring reflect the elevated population prevalence, strong familial aggregation, and multi-lineal transmission pattern of schizophrenia in Palau.

The Pacific Center for Emergency Health--an anatomy of collaborative development and change--the Palau perspective.

Many Pacific Islands Countries (PICs) by their geographic location, isolation, and lack of resources, are at risk for both environmental and man-made disasters. Disaster management (DM) and mitigation is frustrated by the general underdevelopment of DM planning and lack of adequate emergency medical services (EMS) to deal with daily emergencies let alone large-scale emergencies and disasters. To address this, the U.S. Centers for Disease Control and Prevention (CDC) developed and implemented the Pacific Emergency Health Initiative (PEHI) to review and make recommendations regarding the current level of DM/EMS development of select PICs. As a practical next step, a collaborative demonstration project--the CDC--Palau Community College Pacific Center for Emergency Health--was established in the Republic of Palau with the purpose of providing training and technical assistance in DM/EMS development for the region. In September 2001 the Center conducted two simultaneous training programs addressing Public Health Disaster Planning (one-week) and pre-hospital First Responder Care (two-weeks). Sixty participants included public health planners, physicians, and fire and police officials from eleven PIC jurisdictions and representatives from the Secretariat of the Pacific Community, South Pacific Applied Geoscience Commission, and the Fiji School of Medicine. Eleven country and state public health disaster plans were initiated. Post 9-11 the Center has increased relevance. Through CDC's PEHI additional Center training programs are planned through FY 2003.

The Palau AHEC--academizing the public health work plan: capacity development and innovation in Micronesia.

The Palau Area Health Education Center (AHEC)--a program of the University of Hawaii's John A. Burns School of Medicine (JABSOM) and based at Palau Community College--was established in 2001 in response to the recommendations of the 1998 Institute of Medicine (IOM) report--Pacific Partnerships for Health--Charting a New Course for the 21st Century1. One of IOM's core recommendations was to promote the training of the primary health care workforce among the U.S.-Associated Pacific Islands. Since its inception in 2001, the Palau AHEC has coordinated overall 37 postgraduate and undergraduate courses in General Practice and Public Health taught by the University of Auckland Faculty of Medicine and Health Sciences and the Fiji School of Medicine's School of Public Health and Primary Care (SPH&PC) in Palau, Yap State, and the Republic of the Marshall Islands. Currently 139 physicians, nurses, health administrators, and environmental health workers are registered as active students in Palau (58), Yap State (22), and the RMI (59). Notably, the Palau AHEC and the SPH&PC have worked in an innovative partnership with the Palau Ministry of Health to operationalize the MOH's public health work plan to implement a comprehensive community health survey of all 4,376 households in Palau, interviewing 79% of the total population, to determine Palau's health indicators. To accomplish this, the SPH&PC developed and taught a curriculum for Palau physicians and public health nurses on how to design the survey, gather, and analyze data in order to develop and implement appropriately responsive intervention and treatment programs to address Palau's old and newer morbidities. In early FY2005, two other Micronesian AHECs--the Yap State and Commonwealth of the Northern Mariana Islands AHECs--were funded through JABSOM administered grants which will also address the primary care training needs of Micronesia's remote and isolated health workforce.

The Pacific Center for Emergency Health: an anatomy of collaborative development and change--the Palau perspective.

Many Pacific Islands Countries (PICs) by their geographic location, isolation, and lack of resources, are at risk for both environmental and man-made disasters. Disaster management (DM) and mitigation is frustrated by the general underdevelopment of DM planning and lack of adequate emergency medical services (EMS) to deal with daily emergencies let alone large-scale emergencies and disasters. To address this, the U.S. Centers for Disease Control and Prevention (CDC) developed and implemented the Pacific Emergency Health Initiative (PEHI) to review and make recommendations regarding the current level of DM/EMS development of select PICs. As a practical next step, a collaborative demonstration project--the CDC--Palau Community College Center for Emergency Health--was established in the Republic of Palau with the purpose of providing training and technical assistance in DM/EMS development for the region. In September 2001 the Center conducted two simultaneous training programs addressing Public Health Disaster Planning (one-week) and pre-hospital First Responder Care (two-weeks). Sixty participants included public health planners, physicians, and fire and police officials from eleven PIC jurisdictions and representatives from the Secretariat of the Pacific Community, South Pacific Applied Geoscience Commission, and the Fiji School of Medicine. Eleven country and state public health disaster plans were initiated. Through CDC's PEHI additional Center training programs are planned through FY 2003.

In-country and community-based postgraduate family practice training for Micronesian physicians--the Palau AHEC: a collaborative effort.

The U.S. Institute of Medicine in its 1998 review of the health care systems among the U.S.-Associated Pacific Islands (USAPI) identified promotion of primary health care (PHC) and training of the regional health workforce including postgraduate training for physicians as priorities. With the support of the health leadership of the USAPI and the Republic of Palau, the John A. Burns School of Medicine (JABSOM) of the University of Hawaii captured U.S. federal Area Health Education Center (AHEC) funds to implement a postgraduate program to train Family Practitioners - physician specialists in primary care for the region. The Palau AHEC has evolved into ajoint activity of JABSOM, the University of Auckland Faculty of Medicine and Health Sciences (UAFMHS), the School of Public Health & Primary Care--Fiji School of Medicine, and Palau Community College to provide Diploma-level training in Family Practice and Community Health for Micronesian physicians.