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Biomedical subjects

L Slutsker

Publications and source records attributed to L Slutsker.

At least 55 records · Page 3Linked to original sources
PubMed1996

The effect of malaria and malaria prevention in pregnancy on offspring birthweight, prematurity, and intrauterine growth retardation in rural Malawi.

While there is broad evidence for the adverse effects of Plasmodium falciparum infection in pregnancy, and the World Health Organization recommends preventive strategies, there is markedly reduced efficacy in sub-Saharan Africa of the most widely available, affordable and used antimalarial drug for chemoprophylaxis-chloroquine (CQ). During 1987-1990, we studied pregnant women in an area of high malaria endemicity in rural Malawi to compare the efficacy of CQ (the drug recommended by national policy) with mefloquine (MQ, a relatively new and highly effective antimalarial) in preventing low birth weight (LBW) due to prematurity and intrauterine growth retardation (IUGR). Among 1,766 women monitored during at least their last six weeks of pregnancy with observed ingestion of their regimen and facility delivery of a live born singleton, their babies had a mean +/- SD birth weight of 2,905 +/- 461 gm and 16.8% had LBW. In a multivariate analysis, factors significantly associated with LBW included: first birth (odds ratio [OR] = 4.27), female infant (OR = 2.92), maternal human immunodeficiency virus infection (OR = 2.66), low maternal weight (OR = 1.95), and placental blood P. falciparum infection (OR = 1.71). Factors significantly associated with IUGR-LBW included first birth, female infant, low maternal weight, and placental malaria. Factors significantly associated with preterm-LBW included maternal syphilis infection, umbilical cord blood malaria, first birth, low maternal weight, and female infant. Use of an effective antimalarial (MQ) was protective against LBW through its effect on reducing placental and umbilical cord blood malaria infection. The proportion of LBW babies born to women on MQ (12.5% [parity-adjusted for the population of delivering women]) was significantly lower than the proportion born to women on CQ (15.5%; P = 0.05). Effective prevention of malaria in pregnant women in malaria-endemic settings may reduce the likelihood of LBW by 5-14%, and may reduce the amount of preventable LBW by more than 30%. When evaluating antenatal care programs, health policy makers must consider providing an effective preventive drug (either MQ or other drugs identified in additional studies, e.g., sulfa-pyrimethamine compounds) as a means to prevent low birth weight and its consequences.

Adolescent↗
PubMed1996

Malaria treatment and prevention in pregnancy: indications for use and adverse events associated with use of chloroquine or mefloquine.

In sub-Saharan Africa, women frequently report a variety of symptoms during pregnancy, some of which indicate possible illness. Given the adverse impact of malaria in pregnancy, these events may be important for at least two reasons: it may be possible to use reported fever illness as a determinant of which women need an antimalarial intervention, and, it is possible that adverse symptoms following the antimalarial intervention may be important determinants of continued adherence to the prevention regimen. In a cohort of pregnant women enrolled at first antenatal clinic visit in rural Malawi, we evaluated reported fever, determined parasitemia, and placed the women on antimalarial regimens containing chloroquine (CQ) or mefloquine (MQ). We then systematically evaluated reported symptoms following antimalarial drug use after initial therapeutic doses and subsequent prophylactic doses, and monitored women throughout their pregnancy and at delivery. Among 4,187 enrolled women, 1,048 (25%) reported at least one febrile episode during pregnancy before their first antenatal clinic visit. Factors associated with this reported fever included low parity, enrollment in the rainy season, human immunodeficiency virus seropositivity, use of antimalarial prophylaxis before enrollment, high socioeconomic status, normal (compared to low) maternal height and weight, and literacy. Fever before the first antenatal clinic visit was reported by 24.4% of parasitemic women and 25.4% of aparasitemic women; the sensitivity and specificity of fever to identify parasitemic women was 24% and 71%, respectively. In contrast, the sensitivity and specificity of first or second pregnancy to identify parasitemic women was 71% and 57%, respectively. Among women on a CQ or MQ regimen, approximately 60% reported side effects (e.g., itching, dizziness, and gastrointestinal disturbances) after a treatment dose and approximately 25% reported side effects after a prophylactic dose; rates and types of symptoms reported were similar in the CQ and MQ groups. Few serious side effects were observed and rates of fetal loss were low and similar in the groups. Reliance on fever illness will be wholly inadequate to identify parasitemic women; therefore, our findings support existing World Health Organization recommendations that presumptive treatment and prevention regimens should be offered to all pregnant women. When resources are inadequate to offer antimalarial prophylaxis to all pregnant women, women in their first or second pregnancy may be a more appropriate target group than pregnant women with reported fever. Education regarding expected minor side effects may reduce rates of poor compliance and improve the effectiveness of the prevention effort.

Adolescent↗
PubMed1996

Prospective assessment of mortality among a cohort of pregnant women in rural Malawi.

Maternal mortality has recently received attention as a neglected public health problem in many developing countries where mortality rates are estimated to be 8-200 times those in developed countries. Most maternal mortality estimates in sub-Saharan Africa have used retrospective methods because of the lack of large population-based studies. The Mangochi Malaria Research Project, a trial of antimalarial chemoprophylaxis in pregnant women, provided an opportunity to examine prospectively mortality among the study women. Among 4,053 monitored pregnant women, 27 women were known to have died during pregnancy, labor, delivery and the one-year follow-up period. Three women died during the antenatal period and 12 died within six weeks of delivery for an estimated maternal mortality rate of 370 per 100,000 pregnant women; this rate was consistent with rates reported from retrospective surveys in Malawi. Twelve women died between three and 10 months after delivery, and the mortality rate in this nonmaternal period was estimated to be 341 per 100,000. Mortality rates in the maternal and nonmaternal periods were surprisingly similar. Human immunodeficiency virus type-1 (HIV-1) infection and anemia were strongly associated with death in the nonmaternal period. Mortality among infants of mothers who died was 3.7 times higher than the rate of death among infants born to mothers who survived. This study highlights that for rural Malawian women, pregnancy and delivery are risky periods, that the death of the mother adversely affects the survival of her children, and that HIV and anemia are important contributors to nonmaternal mortality in reproductive-age women. Strategies to reduce mortality among women of child-bearing age in sub-Saharan Africa must focus on decreasing the complications of pregnancy and delivery, and address important preventable causes of death, such as anemia and HIV infection.

Cause of Death↗
PubMed1996

Malaria infection in infancy in rural Malawi.

Malaria infection is thought to be relatively infrequent in infants less than 90 days of age in sub-Saharan Africa. In a rural area of Malawi with intense malaria transmission, we examined the occurrence of malaria infection during infancy and risk factors for parasitemia in the first three months of life in the cohort of infants delivered to women in the Mangochi Malaria Research Project. Among 3,915 liveborn singleton infants, 3,432 (87.7%) were seen at least once during infancy (first 12 months of life); of these, malaria blood smear results were available on 2,649 (77.2%). Overall, in a cross-sectional analysis, 23.3% of infants at three months of age were infected with Plasmodium falciparum; this proportion increased to more than 30% during the high transmission season. By the age of 10 months, 60-80% of the infants were infected, depending on the season. Geometric mean parasite density increased each month after two months of age and plateaued at seven months of age. In a life-table analysis, the median time to acquisition of a positive smear was 199 days. Factors independently associated with smear positivity at < 4 months of age included visit during high transmission season (adjusted odds ratio [AOR] = 4.1), maternal smear positivity at the same visit (AOR = 3.5), history of infant fever in the previous two weeks (AOR = 2.8), birth during the rainy season (AOR = 1.7), low socioeconomic status (AOR = 1.6), and low maternal education (AOR = 1.5). The specificity of a recent fever history for malaria infection in early infancy was high (> 70%). Intervention strategies to reduce the risk of early infant infection need to be targeted toward mothers of infants at high risk.

Age Factors↗
PubMed1996

Infant and second-year mortality in rural Malawi: causes and descriptive epidemiology.

Community information based on causes and circumstances of death in infants and young children in Malawi was obtained in a prospective cohort of babies delivered to women enrolled in a malaria-prevention-in-pregnancy study. Vital status information was obtained through home visits every two months; for children who died, questions were asked concerning age and date of death, symptoms preceding death, care sought, location of death (home versus facility), and duration of illness. Of 3,274 liveborn singleton infants, 181, 397, and 152 deaths occurred in the neonatal, postneonatal, and second year of life, respectively. For neonates, proportionate mortality was greatest for sepsis/tetanus (16.7%) and fever (8.6%); however, for more than half of neonatal deaths evaluated the cause was not identified. Up to 30% of neonatal deaths may have been related to prematurity. In the postneonatal period, gastrointestinal illness (39.6%), fever (18.3%), and respiratory illness (14.7%) were the leading causes. Most postneonatal illnesses lasted 1 week or less. Two-thirds of postneonatal deaths occurred outside of a health care facility, although 80% were brought to a facility for care during their illness. Infectious disease syndromes continued to be important in the second year of life, with gastrointestinal (31.6%), fever (23.5%), and measles (20.6%) the most commonly reported causes of death. In this area of rural sub-Saharan Africa, neonatal mortality contributes substantially to infant mortality, and prematurity is considered to be an important component of early neonatal deaths; infectious disease syndromes predominate in the postneonatal and second year of life. Strategies to reduce infant deaths in sub-Saharan Africa must consider these factors, as well as the observations that most children who died had brief illnesses, were taken to a health care facility before death, yet died at home.

Age Factors↗
PubMed1996

Rates and risk factors for mortality during the first two years of life in rural Malawi.

Developing nations in sub-Saharan Africa experience childhood mortality rates that are much higher than any other region of the world. In a rural Malawian community we investigated risk factors for deaths occurring during the neonatal (birth-28 days), postneonatal (29-365 days), infant (birth-365 days), and second-year (366-730 days) periods among a cohort of 3,724 infants monitored from birth. The neonatal mortality rate in this cohort was 48.6 per 1,000 live births (LB); the postneonatal mortality rate was 108.7/1,000 LB. The overall infant mortality rate was 157.3 deaths/1,000 LB and the mortality rate for the first two years of life was 223.7 deaths/1,000 LB. The predominate risk factors for neonatal deaths identified in multivariate analysis were low (hazard ratio [HR] = 2.3) and very low birth weight (HR = 12.7), first pregnancy (HR = 1.8) and maternal syphilis infection (HR = 2.4). Maternal infection with human immunodeficiency virus (HIV) (HR = 1.5) predominated for postneonatal deaths. Low (HR = 1.4) and very low (HR = 5.0) birth weight, first pregnancy (HR = 1.6), maternal HIV infection (HR = 2.4), and the combination of low education and low socioeconomic status (SES) of the mother (HR = 2.0) were the most important factors during the infant period. Maternal HIV infection (HR = 3.3) and the combination of low education and low SES of the mother (HR = 2.6) were the predominate risk factors for mortality occurring during the second year. Factors that were significant in univariate analysis but not significant in the final multivariate models included prematurity, previous adverse reproductive outcome, dying during high malaria transmission season, and being born at home. Interventions to prevent maternal HIV infection and low birth weight and treatment of syphilis infection would have a great impact on reducing early childhood deaths. Improving the delivery of health care and education to women during their first pregnancy and to the most socially disadvantaged women may also help reduce the burden of early childhood mortality in communities such as the one studied in Malawi.

Cohort Studies↗
PubMed1995

Glucocorticoid-suppressible hyperaldosteronism: effects of crossover site and parental origin of chimaeric gene on phenotypic expression.

1. Genetic analysis of five kindreds with glucocorticoid-suppressible hyperaldosteronism, four of whom had not been subjected to any previous genetic analysis, revealed three different crossover breakpoints within the five kindreds clustered in the exon 3-intron 4 region of the chimaeric gene. The site of the crossover point had no effect on blood pressure within the kindreds studied. 2. The gene causing glucocorticoid-suppressible hyperaldosteronism was in strong linkage disequilibrium with an allele of a newly described restriction enzyme polymorphism of the aldosterone synthase gene promoter region, suggesting a possible role for this allele in the development of the chimaeric gene. 3. A novel observation on subjects inheriting glucocorticoid-suppressible hyperaldosteronism from their mothers showed that they had significantly higher plasma aldosterone concentrations and mean arterial blood pressures than those inheriting glucocorticoid-suppressible hyperaldosteronism from their fathers. 4. These results raise the possibility that chronic exposure in utero to elevated plasma aldosterone concentrations may result in the permanent programming of mineralocorticoid-dependent blood pressure regulatory mechanisms, which is amplified in later life by the elevated plasma aldosterone concentrations found in glucocorticoid-suppressible hyperaldosteronism.

Adolescent↗
PubMed1995

Malaria in east African refugees resettling to the United States: development of strategies to reduce the risk of imported malaria.

Resettlement to the United States of malaria-infected refugees can pose problems for both the refugees and their resettlement communities. To formulate malaria management strategies for East African refugees before resettlement to the United States, epidemiologic data were reviewed and malaria prevalence surveys were conducted among refugees awaiting resettlement in Mombasa, Kenya, and Khartoum, Sudan, in 1993. Overall, 279 Somali (Mombasa) and 127 Ethiopian (Khartoum) refugees were surveyed. Malaria contributed significantly to morbidity in Mombasa: 15% (43/279) of Somalis were parasitemic; 39 infections (91%) were due to Plasmodium falciparum. Sulfadoxine-pyrimethamine was effective treatment. In Khartoum, only 0.8% (1/127) were parasitemic; recent fever or antimalarial use were uncommon. Presumptive sulfadoxine-pyrimethamine treatment before departure was recommended for all resettling refugees from Mombasa; in Khartoum, individual assessment of febrile illness was recommended. Prevention of malaria parasitemia by mass drug administration or individual therapy can minimize the burden of malarial illness to refugees and their resettlement communities.

Africa, Eastern↗
PubMed1994

HIV-1 infection among women of reproductive age in a rural district in Malawi.

OBJECTIVES: To determine HIV-1 seroprevalence in pregnant women attending antenatal clinics in a rural district in Malawi, and to estimate the rate of HIV-1 infection in the district among women of reproductive age. DESIGN AND SETTING: Cross-sectional survey conducted from 1987 to 1990 of women enrolled at antenatal clinics at four sites (two towns and two villages). METHODS: Questionnaires were administered and sera screened at delivery. Population infection estimates were based on national census and survey data. RESULTS: Of 3953 pregnant women tested, 283 (7.2%) were HIV-1-seropositive. Women enrolled at town sites were significantly more likely to be HIV-1-infected than village women (11.3 versus 3.9%; P < 0.001). Higher infection rates were associated with age 20-29 years, first or second pregnancy, increased education or socioeconomic status, and living within 8 km of the clinic. It was estimated that over 7300 women of reproductive age were HIV-1-infected in this rural district. CONCLUSIONS: Seroprevalence rates in pregnant women in rural towns were intermediate between rates in villages and previously documented rates in cities in Malawi. Although village sites had lower seroprevalence rates, they accounted for over half the estimated HIV-1 infection in childbearing women in this district.

Adolescent↗
PubMed1994

Use of malaria prevention measures in Malawian households.

Information on malaria prevention practices in households was obtained in a nation-wide knowledge, attitudes, and practices survey in Malawi. Of the 1,531 heads of household questioned, 55% were able to identify mosquitoes as the cause of malaria. Use of any type of malaria prevention method was reported by 52% of respondents. Among users, 47% used commercial products (insecticide, mosquito coils, bednets), and 64% used natural measures (burning leaves, dung, or wood); 11% used both. The most common commercial measure used was mosquito coils (16%) followed by insecticide spray (11%) and bednets (7%). Increasing household income and educational level of the household head were strongly correlated with use of commercial methods to prevent malaria; households with an income ranked moderate or greater were eight times more likely to have used a purchased product. Use of natural measures was correlated with lower income and educational level. Thirty-six percent of respondents reported having heard or seen information on malaria in the previous year. Use of household malaria preventive measures in Malawi is very low and income-dependent. Educational messages are required to improve understanding and use of affordable measures.

Adult↗
PubMed1994

Treatment of malaria fever episodes among children in Malawi: results of a KAP survey.

Caretakers of children (< 10 years of age) were questioned about management of pediatric malarial fever episodes in a nation-wide knowledge, attitudes, and practices survey conducted in Malawi. A total of 1,531 households in 30 randomly selected clusters of 51 households each were sampled and interviewed. Overall 557 caretakers reported a fever in their child in the previous 2 weeks; 43%-judged the illness as severe. Fifty-two percent of caretakers brought their febrile children to clinic. Clinic attendance was positively correlated with young age of the child (< 4 years), severe illness, and higher socioeconomic status. Seventy-four percent of clinic attenders gave their child an antimalarial; in contrast, only 42% of those not attending clinic gave an antimalarial. Optimal therapy (administration of an antimalarial promptly and at the proper dosage) was received by only 7% of febrile children. Children taken to clinic were twice as likely to receive optimal therapy as were non-attenders. Identification of critical points in the optimal therapy algorithm and characteristics of caretakers linked with sub-optimal therapy may help malaria control programs target specific groups and health education messages to improve treatment of malaria fever episodes.

Algorithms↗
PubMed1993

Mutations in the CYP11B1 gene causing congenital adrenal hyperplasia and hypertension cluster in exons 6, 7, and 8.

Steroid 11 beta-hydroxylase deficiency (failure to convert 11-deoxycortisol to cortisol) is the second most common cause of congenital adrenal hyperplasia and results in a hypertensive form of the disease. The 11 beta-hydroxylase enzyme is encoded by the CYP11B1 gene on chromosome 8q22. Two mutations in CYP11B1 have previously been reported in patients with 11 beta-hydroxylase deficiency--Arg-448-->His and a 2-bp insertion in codon 394. We now report eight previously uncharacterized mutations causing this disorder. Seven are point mutations (three nonsense and four missense) and one is a single base pair deletion causing a frameshift. We have used an in vitro transfection assay to show that all five known missense mutations causing 11 beta-hydroxylase deficiency abolish enzymatic activity. In principle, deletions of CYP11B1 could be generated by unequal crossing-over between CYP11B1 and the adjacent CYP11B2 gene, but no such deletions were found among the deficiency alleles in this study. Seven of the 10 known mutations are clustered in exons 6-8, a nonrandom distribution within the gene. This may reflect the location of functionally important amino acid residues within the enzyme or an increased tendency to develop mutations within this region of the gene.

Adrenal Hyperplasia, Congenital↗
PubMed1993

Epidemiology of extrapulmonary tuberculosis among persons with AIDS in the United States.

AIDS surveillance data reported to the Centers for Disease Control from January 1981 through December 1991 were analyzed in a study characterizing persons with human immunodeficiency virus (HIV) infection and extrapulmonary tuberculosis (EPTB) in the United States. Among 206,392 persons reported to have AIDS, 4,751 (2.3%) were also reported to have EPTB; of these cases, 4,257 (90%) were reported after September 1987, when the case definition for AIDS was revised to include EPTB. Seventy-six percent of persons in whom AIDS and EPTB were reported after this revision were born in the United States; among these persons, the annual percentage with EPTB in 1988-1991 ranged from 2.3% to 2.5%. The South and the Northeast accounted for 73% of EPTB cases in U.S.-born persons. U.S.-born non-Hispanic blacks (odds ratio [OR], 3.3) and U.S.-born Hispanics (OR, 2.1) were more likely than U.S.-born non-Hispanic whites to be reported as having EPTB. Intravenous drug users were at higher risk (OR, 2.9) than men who reported having had sex with other men. With the resurgence of tuberculosis and the continued expansion of the HIV epidemic, these data provide a useful basis for the targeting of efforts to control tuberculosis and to prevent HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1993

Recognizing illicit drug use by pregnant women: reports from Oregon birth attendants.

OBJECTIVES: This study was undertaken to determine the prevalence of recognized prenatal illicit substance abuse and the characteristics of women being identified as illicit drug users in a statewide population-based cohort. METHODS: During a 1-month period, birth attendants of all singleton births in Oregon (n = 3200) were surveyed regarding their knowledge of prenatal illicit drug use by women who gave birth. Birth certificates were linked to surveys after removal of personal identifiers. RESULTS: Illicit drug use was recognized in 5.2% of delivering women. Nearly half had used cocaine, methamphetamine, or heroin. Recognized users were significantly more likely than nonusers to be unwed and to have used tobacco or alcohol, have received inadequate prenatal care, and have public assistance as a source of payment. Drug use was recognized twice as frequently by practitioners who routinely questioned their patients about it compared with those who relied on clinical judgment or the occurrence of complications during pregnancy. Birth certificate reporting identified only 41% of recognized users. CONCLUSIONS: Oregon practitioners are identifying seven times as many drug-using women as can be accommodated by available treatment programs for this population. Increased efforts are needed to ensure the adequacy of resources necessary to cope with the problem as already recognized.

Adult↗
PubMed1992

Glucocorticoid-suppressible hyperaldosteronism results from hybrid genes created by unequal crossovers between CYP11B1 and CYP11B2.

Glucocorticoid-suppressible hyperaldosteronism (GSH) is an autosomal dominant form of familial hypertension. The biochemical abnormalities seen in this disorder may be remedied by administration of dexamethasone, implying that aldosterone synthesis is being abnormally regulated by corticotropin. The final three steps of aldosterone synthesis, 11 beta- and 18-hydroxylation and 18-oxidation, are mediated by a cytochrome P450 in the zona glomerulosa of the adrenal cortex termed CYP11B2. A related isozyme in the zona fasciculata, CYP11B1, is required for cortisol synthesis; this isozyme, which is normally expressed at much higher levels than CYP11B2, only has 11 beta-hydroxylase activity. These isozymes are encoded by genes on human chromosome 8q22. We have now studied four unrelated patients with GSH. We found that each patient has one chromosome that carries three CYP11B genes instead of two. This has presumably been generated by unequal meiotic crossing-over. The extra gene is a hybrid with 5' regulatory and coding regions corresponding to CYP11B1 and 3' coding regions from CYP11B2. The breakpoint is in intron 2 in two cases, intron 3 in one, and exon 4 in one. Cells transfected with hybrid cDNAs containing up to the first three exons of CYP11B1 synthesized aldosterone at levels near that of cells carrying normal CYP11B2, but cells transfected with hybrids containing the first five or more exons of CYP11B1 could not synthesize detectable amounts of aldosterone. These data demonstrate that GSH is caused by expression of a gene that is regulated like CYP11B1 but that encodes a protein able to synthesize aldosterone.

Blotting, Southern↗
PubMed1992

Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency.

Corticosterone methyloxidase II (CMO-II) deficiency is an autosomal recessive disorder of aldosterone biosynthesis, characterized by an elevated ratio of 18-hydroxycorticosterone to aldosterone in serum. It is genetically linked to the CYP11B1 and CYP11B2 genes that, respectively, encode two cytochrome P450 isozymes, P450XIB1 and P450XIB2. Whereas P450XIB1 only catalyzes hydroxylation at position 11 beta of 11-deoxycorticosterone and 11-deoxycortisol, P450XIB2 catalyzes the synthesis of aldosterone from deoxycorticosterone, a process that successively requires hydroxylation at positions 11 beta and 18 and oxidation at position 18. To determine the molecular genetic basis of CMO-II deficiency, seven kindreds of Iranian-Jewish origin were studied in which members suffered from CMO-II deficiency. No mutations were found in the CYP11B1 genes, but two candidate mutations, R181W and V386A, were found in the CYP11B2 genes. When these mutations were individually introduced into CYP11B2 cDNA and expressed in cultured cells, R181W reduced 18-hydroxylase and abolished 18-oxidase activities but left 11 beta-hydroxylase activity intact, whereas V386A caused a small but consistent reduction in the production of 18-hydroxycorticosterone. All individuals affected with CMO-II deficiency were homozygous for both mutations, whereas eight asymptomatic subjects were homozygous for R181W alone and three were homozygous for V386A alone. These findings confirm that P450XIB2 is the major enzyme mediating oxidation at position 18 in the adrenal and suggest that a small amount of residual activity undetectable in in vitro assays is sufficient to synthesize normal amounts of aldosterone.

Base Sequence↗
PubMed1992

Eosinophilia-myalgia syndrome. Natural history in a population-based cohort.

BACKGROUND: To determine the natural history of eosinophilia-myalgia syndrome, we followed up all patients with eosinophilia-myalgia syndrome reported to the Oregon Health Division, Portland, during the recent epidemic caused by contaminated tryptophan. METHODS: Patients were interviewed by telephone from 1 to 5 months after illness onset and again at least 12 months after onset. Symptoms (type, onset, and duration), overall disability, treatment, and tryptophan lot and dose were assessed for each patient. RESULTS: Information was obtained for 55 (96%) of 57 case-patients: 53 patients completed interviews and two patients had died. For the 53 patients who were interviewed, symptoms with onset more commonly during the first 3 months of illness included severe myalgias, fatigue, generalized weakness, edema, and rash. Symptoms with later onset included paresthesias, muscle cramps, extremity weakness, and alopecia. At 12 months, 41 patients (77%) continued to report fatigue, 36 (68%) weakness, and 34 (64%) myalgias; 26 patients (49%) had difficulty climbing stairs, 23 (43%) had difficulty getting up from a chair, and 15 (28%) had difficulty holding a cup. Higher doses of tryptophan were correlated with more severe disability, both initially (rs = .33) and at follow-up (rs = .42). Although most patients reported improvement in symptoms at 12 months, only 14 (26%) patients reported that they were able to perform all normal daily activities. CONCLUSIONS: Most patients with eosinophilia-myalgia syndrome in this population-based cohort are still symptomatic 1 year after onset, primarily with the complaints reported early in the illness. The association between degree of disability and daily tryptophan dose suggests that ingestion of varying amounts of contaminant may be responsible, in part, for the severity of symptoms experienced by individual patients.

Activities of Daily Living↗