Biomedical subjects

Richard K Severson

Publications and source records attributed to Richard K Severson.

At least 19 recordsLinked to original sources

PubMed2006

Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph).

A role for genetic susceptibility in non-Hodgkin lymphoma (NHL) is supported by the accumulating evidence of common genetic variations altering NHL risk. However, the pattern of NHL heritability remains poorly understood. We conducted a pooled analysis of 10 211 NHL cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) to evaluate NHL risk among those with hematopoietic malignancies in first-degree relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) of NHL and its subtypes were estimated from unconditional logistic regression models with adjustment for confounders. NHL risk was elevated for individuals who reported first-degree relatives with NHL (OR = 1.5; 95% CI = 1.2-1.9), Hodgkin lymphoma (OR = 1.6; 95% CI = 1.1-2.3), and leukemia (OR = 1.4; 95% CI = 1.2-2.7). Risk was highest among individuals who reported a brother with NHL (OR = 2.8; 95% CI = 1.6-4.8) and was consistent for all NHL subtypes evaluated. If a first-degree relative had Hodgkin lymphoma, NHL risk was highest if the relative was a parent (OR = 1.7; 95% CI = 1.0-2.9). If a first-degree relative had leukemia, NHL risk was highest among women who reported a sister with leukemia (OR = 3.0; 95% CI = 1.6-5.6). The pattern of NHL heritability appeared to be uniform across NHL subtypes, but risk patterns differed by specific hematopoietic malignancies and the sex of the relative, revealing critical clues to disease etiology.

Case-Control Studies↗

PubMed2006

Polymorphisms in genes related to bacterial lipopolysaccharide/peptidoglycan signaling and gastric precancerous lesions in a population at high risk for gastric cancer.

As Helicobacter pylori (HP) is a Gram-negative bacterium, we investigated the associations between several functional polymorphisms in genes involved in lipopolysaccharide (LPS) signaling and the prevalence of various stages of gastric premalignant lesions in a Venezuelan population. The two NOD2 polymorphisms, del3020insC and Gly908Arg, were too infrequent to study their associations with gastric lesions. The risk of intestinal metaplasia (IM) was significantly increased among subjects with the CD14 T-260 allele compared to those without this allele. A similar, but nonsignificant increase in risk for dysplasia was observed among homozygotes of this allele. There was no association between TLR4 Asp299Gly polymorphism and any type of lesions, except for a slight nonsignificant increase in risk of IM associated with the AA genotype among subjects with a higher histological HP score. These results suggest that genetic polymorphisms in HP LPS signaling may be implicated in the development of intermediate stages of gastric premalignant lesions.

Adult↗

PubMed2006

Cellular telephones and non-Hodgkin lymphoma.

Dramatic increase in hand-held cellular telephone use since the 1980s and excess risk of lymphoproliferative malignancies associated with radio-frequency radiation (RFR) exposures in epidemiological and experimental studies motivated assessment of cellular telephones within a comprehensive US case-control investigation of non-Hodgkin lymphoma (NHL). A questionnaire ascertained cellular telephone use in 551 NHL cases and 462 frequency-matched population controls. Compared to persons who had never used cellular telephones, risks were not increased among individuals whose lifetime use was fewer than 10 (odds ratio (OR) = 0.9, 95% confidence intervals (CI): 0.6, 1.3), 10-100 (OR = 1.0, 95 % CI: 0.7, 1.5) or more than 100 times (e.g., regular users, OR = 0.9, 95% CI: 0.6, 1.4). Among regular users compared to those who had never used hand-held cellular telephones, risks of NHL were not significantly associated with minutes per week, duration, cumulative lifetime or year of first use, although NHL was non-significantly higher in men who used cellular telephones for more than 8 years. Little evidence linked use of cellular telephones with total, diffuse large B-cell lymphoma or follicular NHL. These findings must be interpreted in the context of less than 5% of the population reporting duration of use of 6 or more years or lifetime cumulative use of 200 or more hours.

Adult↗

PubMed2006

Host-bacterial interaction in the development of gastric precancerous lesions in a high risk population for gastric cancer in Venezuela.

Helicobacter pylori (HP) infection affects over 50% of the world's population. The prevalence is over 90% in populations at high risk for gastric cancer, but clinical outcomes of the infection are highly variable and thus host genetic factors have been suggested to play a role in its outcomes in addition to bacterial factors. In this study, we examined the effects of common functional genetic polymorphisms of several proinflammatory cytokines known to be overexpressed in HP-infected gastric mucosa on the risk of various stages of gastric premalignant lesions. The odds ratios (ORs) and 95% confidence intervals (CI) for atrophic gastritis, intestinal metaplasia and dysplasia were estimated by multinominal logistic regression analysis among 2,033 Venezuelan subjects. There was a significant effect of IL8 -251A allele on the prevalence of dysplasia (p = 0.021). The OR associated with the A-allele was 1.34 (95% CI: 0.82-2.18) for heterozygotes and 2.00 (95% CI: 1.13-3.56) for homozygotes, compared with the TT genotype. Furthermore, there was a statistically significant interaction between the number of A-alleles and HP cag A genotype (p = 0.009), suggesting that the A-allele increased the risk of dysplasia only when cag A was present. The OR for the AA compared with TT genotype was 3.22 (95% CI: 1.60-6.52) in this group. There were no associations with other proinflammatory cytokines studied, i.e., IL1 beta, IL6, monocyte chemoattractant protein 1 (MCP1) and TNF alpha, or with other stages of premalignant lesions. The present study provides important evidence suggesting host-bacterial interactions in the development of gastric precancerous lesions.

Alleles↗

PubMed2006

Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma.

Profound disruption of immune function is an established risk factor for non-Hodgkin lymphoma. We report here a large-scale evaluation of common genetic variants in immune genes and their role in lymphoma. We genotyped 57 single nucleotide polymorphisms (SNP) from 36 candidate immune genes in 1,172 non-Hodgkin lymphoma cases and 982 population-based controls from a US multicenter study. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the association between individual SNP and haplotypes with non-Hodgkin lymphoma overall and five well-defined subtypes. A haplotype comprising SNPs in two proinflammatory cytokines, tumor necrosis factor-alpha and lymphotoxin-alpha (rs1800629, rs361525, rs1799724, rs909253, and rs2239704), increased non-Hodgkin lymphoma risk overall (OR, 1.31; 95% CI, 1.06-1.63; P = 0.01) and notably for diffuse large B cell (OR, 1.64; 95% CI, 1.23-2.19; P = 0.0007). A functional nonsynonymous SNP in the innate immune gene Fc gamma receptor 2A (FCGR2A; rs1801274) was also associated with non-Hodgkin lymphoma; AG and AA genotypes were associated with a 1.26-fold (95% CI, 1.01-1.56) and 1.41-fold (95% CI, 1.10-1.81) increased risk, respectively (P(trend) = 0.006). Among non-Hodgkin lymphoma subtypes, the association with FCGR2A was pronounced for follicular and small lymphocytic lymphomas. In conclusion, common variants in genes influencing proinflammatory and innate immune responses were associated with non-Hodgkin lymphoma risk overall and their effects could vary by subtype. Our results require replication but potentially provide important clues for investigating common genetic variants as susceptibility factors and in disease outcomes, treatment responses, and immunotherapy targets.

Adult↗

PubMed2006

Significance of micrometastases on the survival of women with T1 breast cancer.

BACKGROUND: The most important factor in predicting survival among women with newly diagnosed breast cancer is the status of the axillary lymph nodes. Although straightforward to define, the impact of micrometastases on survival remains to be completely determined. METHODS: A review of data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute was performed using 43,921 cases diagnosed from January 1988 through December 2001. Among women with invasive breast carcinomas <or=2 cm undergoing a resection of the primary malignancy and an axillary lymph node dissection, there were 42,197 cases without lymph node metastases and 1724 cases with micrometastases. Survival differences among these 2 groups were evaluated and are reported here. RESULTS: Survival at 12 years was modestly affected by the presence of either solitary (5.0%) or multiple lymph nodes (3.6%) with micrometastases when compared with lymph node-negative cases. In subgroup analyses, the decreased survival associated with micrometastases was inconsistent. The most significant survival disadvantage associated with micrometastases was found in cases with Grade 3 carcinomas. CONCLUSIONS: The modest and variable impact of micrometastases on long-term survival indicates that micrometastases are an important, but not a dominant, prognostic indicator.

Aged↗

PubMed2006

Risk of non-Hodgkin lymphoma (NHL) in relation to germline variation in DNA repair and related genes.

Chromosomal translocations, insertions, and deletions are common early events in non-Hodgkin lymphoma (NHL) carcinogenesis, and implicated in their formation are endogenous processes involved in antigen-receptor diversification, such as V(D)J recombination. DNA repair genes respond to the double- and single-strand breaks induced by these processes and may influence NHL etiology. We examined 34 genetic variants in 19 genes within or related to 5 DNA repair pathways among 1172 cases and 982 matched controls who participated in a population-based NHL study in Los Angeles, Seattle, Detroit, and Iowa from 1998 to 2000. Cases were more likely than controls to have the RAG1 820 R/R (odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.4 to 5.0) than Lys/Lys genotypes, with evidence of a gene dosage effect (P trend < .001), and less likely to have the LIG4 (DNA ligase IV) 9 Ile/Ile (OR = 0.5; 95% CI = 0.3 to 0.9) than T/T genotype (P trend = .03) in the nonhomologous end joining (NHEJ)/V(D)J pathway. These NHEJ/V(D)J-related gene variants represent promising candidates for further studies of NHL etiology and require replication in other studies.

DNA Repair↗

PubMed2006

Genetic determinants of bone mass do not relate with breast cancer risk in US white and African-American women.

INTRODUCTION: The association between high bone mass and increased breast cancer risk has been established. Identification of polymorphisms and the resultant variant receptors suggests the possibility of differential effects on hormone responsive genes when complexed with the hormones. Both estrogen receptor-alpha (ER) and vitamin D receptor (VDR) polymorphisms have been associated with bone density. Thus, we examined these polymorphisms for association with increased breast cancer risk among US African-American and white women. METHODS: A case-control study was conducted to measure ER and VDR polymorphisms and radial bone mineral density (BMD) in African-American and white women, and to examine the association between polymorphisms, bone density and breast cancer risk. Genotypes and bone density were obtained from 412 women (220 cases and 192 controls, with equal distribution between the two ethnic groups). RESULTS: We found no evidence for an association between either the ER or VDR genotypes and breast cancer risk. Also, there was no difference in the risk of breast cancer by genotypes after adjusting for ethnicity. The addition of age, sex and ethnicity-specific BMD (Z-scores) did not significantly change the odds ratio for breast cancer. CONCLUSIONS: Our data suggest that the polymorphisms investigated had no effect on risk of breast cancer in this population. Thus, we found no evidence to support our hypothesis that breast cancer cases and controls would have a different distribution of ER and VDR genotypes. Furthermore, the polymorphisms were not associated with differences in bone mass and its relationship with breast cancer risk.

Adult↗

PubMed2006

Cyclin D1 splice variant and risk for non-Hodgkin lymphoma.

To investigate the role of cell cycle gene variations in lymphomagenesis, we evaluated associations (odds ratios [OR] and 95% confidence intervals [CI]) in polymorphisms from seven candidate genes in 1,172 non-Hodgkin lymphoma (NHL) cases and 982 population-based controls. The cyclin D1 (CCND1) splice variant G870A (rs603965) increased NHL risk (OR(AA) = 1.4, 95% CI = 1.1-1.8, P-trend = 0.021), which was consistent for four B-cell subtypes. As CCND1 expression indicates poor NHL prognosis, our results, if true, would support its potentially dual importance in NHL etiology and survival.

Adult↗

PubMed2006

Asthma history, occupational exposure to pesticides and the risk of non-Hodgkin's lymphoma.

We previously reported that, although asthma did not increase the risk of non-Hodgkin's lymphoma (NHL), the risk from pesticide exposures was higher among asthmatics than that among nonasthmatics. To further evaluate this finding, we analyzed data from a population-based case-control study of NHL conducted in Iowa, Detroit, Los Angeles and Seattle. Cases (n = 668) diagnosed with NHL from 1998 to 2000 and controls (n = 543) randomly selected from the same geographical areas as that of the cases were included in this analysis. Odds ratios (OR) for the risk of NHL from potential occupational exposure to pesticides tended to be higher among asthmatics (OR = 1.7; 95% CI 0.3-9.1) when compared with that among nonasthmatics (OR = 0.9; 95% CI 0.6-1.5). The risks of NHL associated with pesticide exposure were also higher among asthmatics who had history of hospitalization (OR = 2.1; 95% CI 0.2-29.0) or daily medication for asthma (OR = infinite) than those among asthmatics who did not have such histories. Our results support the previous finding that the risk of NHL from pesticide exposure may be greater among asthmatics.

Adult↗

PubMed2006

Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma.

Evidence supporting the contribution of oxidative stress to key pathways in cancer, such as inflammation and DNA damage, continues to mount. We investigated variations within genes mediating oxidative stress to determine whether they alter risk for non-Hodgkin lymphoma (NHL). Thirteen single nucleotide polymorphisms (SNPs) from 10 oxidative stress genes (AKR1A1, AKR1C1, CYBA, GPX, MPO, NOS2A, NOS3, OGG1, PPARG and SOD2) were genotyped in 1172 NHL cases and 982 population-based controls from a USA multicenter case-control study. For NHL and five subtypes (diffuse large B-cell, follicular, marginal zone, small lymphocytic and T-cell), SNP associations were calculated. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for sex, age (<45, 45-64, 65+ years), race (white, black, other) and study site. Overall, the oxidative stress pathway was associated significantly with the B-cell NHL subtype, diffuse large B-cell lymphoma (DLBCL) (global P-value=0.003). Specifically, for nitric oxide synthase (NOS2A Ser608Leu, rs2297518) Leu/Leu homozygotes, there was a 2-fold risk increase for NHL (OR=2.2, 95% CI=1.1-4.4) (referent=Ser/Ser and Ser/Leu). This risk increase was consistent by cell lineage (B- and T-cell NHL) and pronounced for the two most common subtypes, diffuse large B-cell (OR=3.4, 95% CI=1.5-7.8) and follicular lymphoma (OR=2.6, 95% CI=1.0-6.8). In an analysis of manganese superoxide dismutase (SOD2 Val16Ala, rs1799725) Ala/Ala homozygotes, we observed moderately increased risks for B-cell lymphomas (OR=1.3, 95% CI=1.0-1.6; referent=Val/Val and Val/Ala) that was consistent across the B-cell subtypes. Genetic variations that result in an increased generation of reactive oxygen species appear to increase risk for NHL and its major subtypes, particularly DLBCL. Independent replication of our findings are warranted and further evaluation of oxidative stress in the context of inflammation, DNA repair and the induction of the NF-kappaB pathway may further reveal important clues for lymphomagenesis.

Adult↗

PubMed2006

Ultraviolet radiation, dietary vitamin D, and risk of non-Hodgkin lymphoma (United States).

OBJECTIVE: Because of conflicting findings about the relationship between ultraviolet (UV) radiation and the risk of non-Hodgkin lymphoma (NHL), we evaluated the risk of several indicators related to UV, including two not previously studied: dietary vitamin D, and ambient UV levels by residential location. METHODS: As part of a case-control study conducted in four Surveillance, Epidemiology, and End Results (SEER) registries, we collected UV information from a self-administered questionnaire and computer-assisted personal interview with 551 NHL cases and 462 controls. We estimated the relative risk (RR) and 95% confidence intervals (CI) from unconditional logistic regression models. RESULTS: Eye color, a marker of host susceptibility to UV, showed a decreasing risk gradient for lightest eyes (0.47) compared to darkest. Relative risks were in the range of 0.73-0.78 for participants reporting more hours in the mid-day summer sun. Use of sunlamps or tanning booths was associated with decreased risk (RR = 0.88), as was estimated overall ambient UV (RR = 0.76 per 50 RB-units) overall. Vitamin D intake from diet and supplements was not related to risk. Results were thus consistent for the various indicators, although some estimated risks were not statistically significant. Effects were generally similar for diffuse large B-cell (DLBCL) and follicular lymphomas. CONCLUSION: These data suggest a slight protective effect of sunlight against NHL, and they agree with geographic patterns of NHL incidence observed in the US.

Adult↗

PubMed2006

Genetic polymorphisms in anti-inflammatory cytokine signaling and the prevalence of gastric precancerous lesions in Venezuela.

OBJECTIVES: The aim of the study was to assess the effects of genetic polymorphisms in anti-inflammatory mediators, i.e., IL10, IL4 and IL4R on the prevalence of gastric precancerous lesions and their interactions with other environmental factors. METHODS: The study population consisted of 2,033 Venezuelan subjects known to have extremely high Helicobacter Pylori (HP) infection rates. The odds ratios (OR) and 95% confidence intervals (CI) associated with these polymorphisms were estimated by multinominal logistic regression models for gastric precursor lesions. RESULTS: We found a 60% increase in risk of intestinal metaplasia (IM) and dysplasia combined (OR 1.62, 95% CI: 1.10-2.38) among the carriers of the IL10-1082 low activity allele. This increased risk was more pronounced for dysplasia than for IM. On the other hand, homozygotes with the low activity allele of the A398G polymorphism in the IL4R gene had a modest increase in risk of atrophic gastritis (OR = 1.52, 95% CI: 1.05-2.21), compared with homozygotes of the high activity allele. There were no statistically significant synergetic interactions between these polymorphisms and environmental risk factors (low fruit intake, high starchy vegetable intake and cigarette smoking) for these lesions. CONCLUSION: While the results of the present study suggest roles of genetic variability in these anti-inflammatory mediators in different stages of gastric carcinogenesis, there is high likelihood that they were chance findings due to multiple comparisons.

Adult↗

PubMed2006

Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium.

BACKGROUND: Common genetic variants in immune and inflammatory response genes can affect the risk of developing non-Hodgkin lymphoma. We aimed to test this hypothesis using previously unpublished data from eight European, Canadian, and US case-control studies of the International Lymphoma Epidemiology Consortium (InterLymph). METHODS: We selected 12 single-nucleotide polymorphisms for analysis, on the basis of previous functional or association data, in nine genes that have important roles in lymphoid development, Th1/Th2 balance, and proinflammatory or anti-inflammatory pathways (IL1A, IL1RN, IL1B, IL2, IL6, IL10, TNF, LTA, and CARD15). Genotype data for one or more single-nucleotide polymorphisms were available for 3586 cases of non-Hodgkin lymphoma and for 4018 controls, and were assessed in a pooled analysis by use of a random-effects logistic regression model. FINDINGS: The tumour necrosis factor (TNF) -308G-->A polymorphism was associated with increased risk of non-Hodgkin lymphoma (p for trend=0.005), particularly for diffuse large B-cell lymphoma, the main histological subtype (odds ratio 1.29 [95% CI 1.10-1.51] for GA and 1.65 [1.16-2.34] for AA, p for trend <0.0001), but not for follicular lymphoma. The interleukin 10 (IL10) -3575T-->A polymorphism was also associated with increased risk of non-Hodgkin lymphoma (p for trend=0.02), again particularly for diffuse large B-cell lymphoma (p for trend=0.006). For individuals homozygous for the TNF -308A allele and carrying at least one IL10 -3575A allele, risk of diffuse large B-cell lymphoma doubled (2.13 [1.37-3.32], p=0.00083). INTERPRETATION: Common polymorphisms in TNF and IL10, key cytokines for the inflammatory response and Th1/Th2 balance, could be susceptibility loci for non-Hodgkin lymphoma. Moreover, our results underscore the importance of consortia for investigating the genetic basis of chronic diseases like cancer.

Case-Control Studies↗

PubMed2006

Residential insecticide use and risk of non-Hodgkin's lymphoma.

Previous studies have linked non-Hodgkin's lymphoma (NHL) with occupational exposure to insecticides, but residential use is largely unexplored. In this population-based case-control study, we examined NHL risk and use of insecticides in the home and garden. We identified NHL cases, uninfected with HIV, diagnosed between 1998 and 2000 among women and men ages 20 to 74 years in Iowa and the metropolitan areas of Los Angeles, Detroit, and Seattle. Controls were selected using random digit dialing or Medicare files. Computer-assisted personal interviews (1,321 cases and 1,057 controls) elicited data on insecticide use at each home occupied since 1970. Insecticide levels were measured in dust taken from used vacuum cleaner bags (682 cases and 513 controls). We previously reported a positive association with dichlorodiphenyldichloroethylene levels in carpet dust residues. Here, we focus on insecticides that were commonly used after 1970, the time period covered by our questionnaire. People whose homes were treated for termites had elevated NHL risk (odds ratio, 1.3; 95% confidence interval, 1.0-1.6). Risk was modestly, although not significantly, elevated in all but one study center and in all sexes and races. The elevation in risk was restricted to people whose homes were treated before the 1988 chlordane ban. There was a significant trend of increasing risk with increasing levels of alpha-chlordane residues in dust (P(trend) = 0.04) and a marginally significant trend for gamma-chlordane (P(trend) = 0.06). We found no evidence of associations for insects overall, for specific types of insects other than termites, or for elevated residues of other insecticides. We concluded that chlordane treatment of homes for termites may increase residents' NHL risk.

Adult↗

PubMed2006

Metabolic gene variants and risk of non-Hodgkin's lymphoma.

Genes involved in metabolism of environmental chemical exposures exhibit sequence variability that may mediate the risk of non-Hodgkin's lymphoma. We evaluated associations between non-Hodgkin's lymphoma and 15 variants in AHR, CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2E1, GSTP1, GSTM3, EPHX1, NQO1, and PON1. Cases were identified from four Surveillance, Epidemiology, and End Results registries in the United States, and population-based controls were identified through random-digit dialing and Medicare eligibility files. Metabolic gene variants were characterized for the 1,172 (89% of total) cases and 982 (93%) controls who provided biological samples for genotyping. Subjects who were heterozygous or homozygous for the cytochrome P450 gene variant CYP1B1 V432L G allele were at slightly greater risk of non-Hodgkin's lymphoma [odds ratio (OR), 1.27; 95% confidence interval (95% CI), 0.97-1.65]; these results were consistent across B-cell lymphoma subtypes and among both non-Hispanic White and Black subjects, although not statistically significant. The CYP2E1 -1054T allele was associated with decreased risk of non-Hodgkin's lymphoma (CT and TT genotypes combined OR, 0.59; 95% CI, 0.37-0.93), and this pattern was observed among all histologic subtypes. The numbers of cases of particular subtypes were rather small for stable estimates, but we noted that the PON1 L55M AA allele, associated with slightly increased risk of non-Hodgkin's lymphoma (variant homozygotes OR, 1.36; 95% CI, 0.96-1.95), was most strongly associated with follicular non-Hodgkin's lymphoma and T-cell lymphoma, with ORs for variant homozygotes of 2.12 and 2.93, respectively. There was no overall association with non-Hodgkin's lymphoma for the other gene variants we examined. The modest effects we observed may reflect the context of exposures within the general population represented in our study.

Adult↗

PubMed2006

Exploring physician and staff perceptions of the learning environment in ambulatory residency clinics.

BACKGROUND AND OBJECTIVES: Investigations of teaching quality in ambulatory clinics have generally focused on faculty and medical student perspectives. We investigated the association of learning and organizational environment variables with faculty, resident, and nursing staff perceptions of quality of teaching and with a measure of resident learning in ambulatory residency clinics. METHODS: Annually over 5 years (1998-2002), we distributed learning and organizational environment surveys to faculty, residents, and staff in three ambulatory clinics of the Wayne State University Department of Family Medicine. We assessed internal reliability of the surveys' 11 scales and then compared responses of employee groups across sites. We then conducted a multiple regression analysis to determine the association of learning and organizational environment variables with faculty, resident, and staff perceptions of quality of teaching. We also compared the mean change in residents' In-training Examination (ITE) scores at our clinic teaching sites over the years of the study. RESULTS: Nine of 11 survey scales demonstrated acceptable internal reliability. Staff views were significantly lower than residents' views on all scales and were significantly lower than faculty's on all but one scale. Opinions about availability of learning opportunities for residents explained the most variance (35.2%) in the overall assessment of teaching quality. The addition of job satisfaction brought the explained variance up to 46.4%. The mean change in ITE scores was higher for residents at the site with higher learning and organizational environment assessment scores but not significantly so. CONCLUSIONS: Nine learning and organizational environment scales were found internally reliable and useful to measure faculty, resident, and staff perspectives on ambulatory teaching sites. Two areas of focus for improvement were found. First, learning opportunities should be structured so that residents are oriented to the ambulatory clinic, have their knowledge assessed regularly, are helped to meet individual goals, are given appropriate levels of responsibility, and see an adequate number, mix, and continuity of patients. Second, prioritizing efforts to improve job satisfaction for all employees is important because of the association between job satisfaction and employee perceptions of quality of teaching. We recommend that research into the educational climate in ambulatory clinics include perspectives of the full range of clinic personnel who can contribute to resident learning.

Ambulatory Care Facilities↗

PubMed2005

Antibodies to JC and BK viruses among persons with non-Hodgkin lymphoma.

Two related polyomaviruses, JC virus (JCV) and BK virus (BKV), commonly cause lifelong infections in humans, with periodic reactivation manifesting as viral shedding in urine. Because JCV can infect lymphocytes and cause chromosomal damage, it is a plausible candidate to cause non-Hodgkin lymphoma (NHL). To test this hypothesis, we measured IgG antibodies to JCV and BKV capsids using a virus-like particle enzyme immunoassay in 3 separate groups of subjects. First, in a U.S. population-based case-control study of NHL (724 cases, 622 controls), we found lower JCV antibody levels in cases than controls (median optical density = 0.12 vs. 0.21, p < 0.0001); likewise, JCV seroprevalence was lower in cases (49% vs. 59%, adjusted odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.56-0.87). In contrast, BKV antibody levels did not differ between groups. Second, we found that JCV and BKV antibody levels changed little over time among 24 NHL patients receiving chemotherapy. Third, we evaluated 126 homosexual men, of whom 46 were shedding JCV and 14 were shedding BKV in urine. Antibody levels were much higher in shedders than non-shedders (JCV: median optical density = 0.67 vs. 0.07, p < 0.0001; BKV: 0.87 vs. 0.40, p = 0.003), indicating that these antibodies are a marker for viral replication. Because no deficit of BKV antibody was seen in NHL cases, and because antibody levels did not change materially with chemotherapy, we suggest that the lower levels of JCV antibody observed in NHL patients may not be due entirely to a disease or treatment effect. Additional research is needed to determine whether JCV replication is decreased in individuals with NHL and whether these findings are consistent with an etiologic role for JCV in NHL.

Adult↗