Epigenomic changes during leukemia cell differentiation: analysis of histone acetylation and cytosine methylation using CpG island microarrays.

Dysregulation of epigenetic control is an important participant in carcinogenesis. The PML/RAR alpha translocation in acute promyelocytic leukemia (APL) is an example where the resultant fusion protein recruits histone deacetylase complexes to target genes resulting in their inappropriate transcriptional repression. All-trans-retinoic acid (ATRA) acts as a ligand that relieves this repression and produces an epigenetic transcriptional reprogramming of the cancer cell. CpG island microarrays were used to analyze the DNA methylation and histone acetylation state of the human APL cell line NB4 before and after differentiation with ATRA as well as normal peripheral blood mononuclear cells (PBMC). Over 70 CpG islands within 1 kb of transcription start of a known gene are aberrantly methylated in NB4 cells compared with PBMC; however, no changes in cytosine methylation were detected following ATRA-induced differentiation. With respect to histone H4 acetylation, over 100 single-copy CpG islands within 1 kb of transcription start of a known human gene became hyperacetylated following ATRA-induced differentiation. One CpG island was aberrantly methylated in NB4 cells, but became hyperacetylated and was induced following ATRA treatment and was associated with the HoxA1 gene, suggesting it may be a target gene of ATRA in APL. In addition to single-copy sequences, a selective increase in acetylation was detected in satellite DNA when compared with other high-copy sequences, such as Alu or rDNA. In summary, ATRA stimulates complex epigenomic changes during leukemic cell differentiation, and monitoring these changes may help to identify new targets of epigenetic dysfunction.

Project LID (lower infant deaths). Lessons learned from a local infant mortality review project.

Project LID (Lower Infant Deaths) is an infant mortality review project conducted by the Minneapolis Department of Health and Family Support and the Saint Paul-Ramsey County Department of Public Health. Infant death occurs when a live-born infant dies before age 1. Multidisciplinary teams reviewed 112 infant-mother cases involving infant death using vital and medical records. Open-ended maternal interviews were conducted for approximately half of the cases. This combination of quantitative and qualitative data provided insights into the contributing social, medical, and environmental factors experienced by some families in Hennepin and Ramsey counties. Case review teams developed recommendations to address factors identified in each case. Recommendations are directed to health care providers, professional societies, health systems, government organizations, policymakers, and community- and school-based organizations. This article describes findings from the project and presents recommendations for Minnesota physicians with practices in obstetrics, family medicine, and pediatrics.

Barriers to screening and counseling pregnant women for alcohol use.

The consequences of fetal alcohol exposure are far-reaching and preventable. Health care providers are uniquely positioned to promote alcohol-free pregnancy, yet an array of factors inhibit routine screening, counseling, and referral. This descriptive, qualitative study explored experiences and perceived barriers related to prenatal screening for alcohol use. The study included eight focus groups (71 participants) and 41 key informant interviews with health care professionals representing a mix of disciplines. Nearly 40% of the providers were physicians who regularly encounter women in their practices. While most providers ask about alcohol use, few probe in depth or follow up. The findings should alert program planners and medical educators to strengthen their preventive medical and public health practices.

Screening for tuberculosis infection among secondary school students in Minneapolis-St. Paul: policy implications.

Three students in the St. Paul Public Schools were diagnosed with active tuberculosis (TB) in late 1991 and early 1992. To define the prevalence of TB infection in St. Paul and Minneapolis, we conducted school-based screening projects in the St. Paul and Minneapolis public schools during 1992 and 1993. In St. Paul, 7,596 (74.8%) students in grades six through 12 received Mantoux tests; 268 (3.5%) were reactive. Infection rates varied significantly by country of birth, with students born outside the United States more likely to be Mantoux reactors than U.S.-born students (RR = 20.2; 95% CI = 14.9-27.3; p < 0.001). In Minneapolis, 752 (47.2%) eighth-grade students received Mantoux tests; 23 (3.1%) were reactive. As in St. Paul, infection rates varied by country of birth; students born outside the United States were more likely to have reactive Mantoux tests than students born in this country (RR = 13.2; 95% CI = 5.6-31.4; p < 0.001). We conclude that routine TB screening of school students is not warranted in Minnesota, although school-based screening targeted at the highest risk students, particularly those born outside the United States, may be a beneficial prevention strategy.

Working with refugee survivors of torture.

Numerous factors must be taken into account to best provide for the health and well-being of refugee patients in developed countries. One issue that is rarely considered is the awful and not uncommon occurrence of political torture. Large numbers of refugees and other displaced persons are survivors of political torture, and health care professionals must be prepared for this possibility when treating refugee patients. The effects of torture are pervasive, and we provide some practical considerations for health professionals who care for survivors of torture. Specific challenges include problems relating to exile and resettlement, somatic symptoms and pain, and the "medicalization" of torture sequelae.

A snapshot of tuberculosis in urban Minnesota.

We reviewed the records of all 66 cases of tuberculosis in St. Paul between 1986 and 1989. Two-thirds of the patients were foreign born. Some of these patients experienced problems in adherence to therapy because of cultural barriers. Resistance of the organism to antituberculosis medications was also a significant problem.

Measles. Forgotten but not gone.

Vaccination has greatly reduced the incidence of measles in the United States. Yet, because of the highly infectious nature and potentially fatal complications of the disease, primary care physicians need to remain alert to possible cases and to react aggressively during an outbreak. Dr Holtan discusses why measles persists, who is at risk, and how immunity is achieved.

Amebiasis. The ancient scourge is still with us.

Amebiasis is usually contracted in geographic areas where sanitation is poor, but outbreaks can still occur anywhere that drinking water becomes contaminated with sewage. In the majority of persons infected with the parasite, colonization of the intestine is asymptomatic. In others, symptoms of gastrointestinal distress can appear within a week. In rare cases, extra-intestinal amebiasis can cause abscesses in the liver or elsewhere. Many questions about the disease course in different patients remain to be answered. Diagnosis can be made through symptom identification; findings of right-upper-quadrant tenderness, leukocytosis, and an elevated level of alkaline phosphatase; and testing the feces for trophozoites or cysts. Clinicians disagree on whether asymptomatic persons need to be treated, but anyone who is capable of transmitting the disease should be advised of how to avoid exposing others to it.

Giardiasis. A crimp in the life-style of campers, travelers, and others.

Once Giardia cysts leave the host, they die quickly if dehydrated but can survive for two months in water as cold as 8 degrees C (46 degrees F). Thus, giardiasis is transmitted through ingestion of infected feces or water. Infection most often causes diarrhea, but if a subacute or chronic form develops, additional signs and symptoms of intestinal distress may be present. Diagnosis is made by finding cysts in a stool sample and/or trophozoites in duodenal fluid. In rare cases, small-bowel biopsy may be necessary. Whether to treat asymptomatic giardiasis is debatable. Drug treatment spares the patient unpleasant symptoms that may develop and eliminates transmission, but available drugs can have side effects and none has been proven safe for pregnant women. By far, the best approach to giardiasis is prevention through education of travelers, nature lovers, and workers in day-care centers and institutions that house the incontinent.

Helminthiasis. Tips for getting rid of unwelcome guests.

Helminthic parasites usually cause uncomplicated infections of the intestine. Complications can arise from nutritional competition between parasite and host, mechanical obstruction of the intestine or common bile duct (in ascariasis), and an overwhelming, fatal infection among immunocompromised hosts (in strongyloidiasis). Diagnosis is made by testing stool samples, except for Enterobius, which can often be seen in the perianal area. Treatment in uncomplicated cases is straightforward and easy. Several drugs are available, and the regimen depends on which parasites are present. However, none is safe for use in pregnant women.

Splenomegaly in Hmong refugees.

We review asymptomatic splenomegaly in Indochinese refugees and provide recommendations for evaluation of the problem. Prevalence of splenomegaly in newly arrived Indochinese refugees was 2.5%, three times more prevalent in the Hmong than in the non-Hmong refugees. Male Hmong refugees aged 15 to 29 years had the highest prevalence (10%). For the 50 Hmong refugees studied, there was no evidence that their splenomegaly was caused by clonorchiasis, schistosomiasis, tuberculosis, syphillis, lymphoma, tropical splenomegaly syndrome, or clinical malaria. Cases were more likely to have hepatomegaly, hepatitis B surface antigen positivity, and a low mean corpuscular volume than a reference population of Hmong refugees. Malaria antibody titers were elevated in all but one of the 41 cases (98%) tested.