Bacterial toxins and enteral feeding of premature infants at risk for necrotizing enterocolitis.

Concordance between gram-negative enteric and other toxin-producing bacteria in blood and stool culture, endotoxin (lipopolysaccharide), and interleukin 6 (IL-6) was measured in 60 preterm infants (600-1600 g) as a clinical index in neonatal necrotizing enterocolitis (NEC). Escherichia coli, Klebsiella, Enterobacter, and Clostridium spp, identified by routine bacteriology, were each strongly associated with elevated concentrations of endotoxin (P < 0.01) in stool filtrates with Clostridium spp most strongly associated with NEC disease. Stool filtrate endotoxin (endotoxin units [EU] per gram) measured by a Limulus amebocyte lysate assay was age-dependent. Samples from stage I NEC (61%) and infants with advanced disease (67%) had notably elevated levels of stool endotoxin (>10 ln EU/g) compared with NEC-negative (47%) samples tested. Plasma and stool IL-6 generally tested at the low, nonmeasurable limit of the enzyme-linked immunosorbent assay (ELISA) for NEC-negative (88%) and stage I NEC (93%), although a small proportion of samples (25%) from infants with stage II or II NEC had elevated stool concentrations of IL-6. We conclude that identification of toxin-producing organisms and endotoxin elevations in stool filtrates are more useful than circulating levels of endotoxin in plasma in predicting mucosally limited disease in the gastrointestinal tract. The prognostic value of monitoring stool endotoxin in infants with overgrowth of gram-negative bacteria has implications for therapeutic strategies for patients with early and advanced stages of disease. Monitoring inflammatory cytokines (IL-6) in relation to endotoxin values in stool appears of limited clinical value in controlling this devastating disease in preterm neonates.

Concordance of bacterial cultures with endotoxin and interleukin-6 in necrotizing enterocolitis.

Concordance between gram-negative enteric and other toxin-producing bacteria in blood and stool culture, endotoxin (lipopolysaccharide), and interleukin-6 (IL-6) was measured in 60 preterm infants (600-1600 g) as a clinical index in neonatal necrotizing enterocolitis (NEC). E. coli, Klebsiella, Enterobacter, and Clostridium spp., identified by routine bacteriology, were each strongly associated with elevated concentrations of endotoxin (P < 0.01) in stool filtrates, with Clostridium spp. most strongly associated with NEC disease. Stool filtrate endotoxin (EU/g) measured by a Limulus amebocyte lysate assay was age dependent. Samples from stage I NEC (61%) and infants with advanced disease (67%) had notably elevated levels of stool endotoxin (> 10 ln EU/g) compared to NEC-negative (47%) samples tested. Plasma and stool IL-6 generally tested at the low, nonmeasurable limit of the ELISA for NEC-negative (88%) and stage I NEC (93%), although a small proportion of samples (25%) from infants with stage II or III NEC had elevated stool concentrations of IL-6. We conclude that identification of toxin-producing organisms and endotoxin elevations in stool filtrates are more useful than circulating levels of endotoxin in plasma in predicting mucosally limited disease in the gastrointestinal tract. The prognostic value of monitoring stool endotoxin in infants with overgrowth of gram-negative bacteria has implications for therapeutic strategies in patients with early and advanced stages of disease. Monitoring inflammatory cytokines (IL-6) in relation to endotoxin values in stool appears of limited clinical value in controlling this devastating disease in preterm neonates.

Sepsis syndrome and associated sequelae in patients at high risk for gram-negative sepsis.

We conducted a prospective surveillance study of 80 hospitals across the United States to determine the incidence of sepsis syndrome and its associated sequelae in hospitalized patients over age 18 years who were administered antibiotics for suspected or documented gram-negative infection. A sample of 1754 hospitalized patients were followed from onset of antimicrobial therapy to discharge or death. Mortality rates (MR) varied depending on the suspected source of sepsis syndrome. For patients in whom the syndrome was associated with community-acquired urinary tract infections, mortality was 20% (relative risk [RR] = 0.51, p < 0.05), for those with trauma 20.6% (RR = 0.51, p < 0.05), and patients with nosocomial respiratory tract infections 57.1% (RR = 1.66, p < 0.05). More than two complications occurred in 65.2% of patients under age 60 years (MR 31%), 40.8% of those age 60-80 (MR 42%), and 35.6% of patients older than 80 years (MR 33.3%, p > 0.05). Various patient populations had significant differences in both the incidence of the syndrome and its complications, and consequent mortality. Perhaps morbidity as well as mortality should be used as outcomes when testing the efficacy of innovative therapies for sepsis.

Reduction of virus shedding by B. bifidum in experimentally induced MRV infection. Statistical application for ELISA.

The protective effect of a human strain of Bifidobacterium bifidum (B. bifidum) against murine group A rotavirus (MRV) was examined in the intestines of BALB/c infected mice. In experiments designed to determine whether B. bifidum mediated MRV shedding during diarrheal disease, pregnant dams (and their expected litters) were randomly assigned to the following groups: (1) mice infected with MRV alone; (2) B. bifidum-treated + MRV-infected mice; (3) B. bifidum-treated controls; and (4) saline control animals. An enzyme-linked immunosorbent assay (ELISA) for the detection of group A rotavirus was used to measure virus protein. The sensitivity of the MRV antigen detector ELISA was determined by serially diluting the rotavirus antigen in test samples. Antigen was detected in dilution ranges of 1:256-1:4096 during the acute phase and 1:16-1:512 in the recovery phase of MRV clinical disease, in the samples tested. Treatment with B. bifidum significantly reduced shedding of MRV antigen (P < 0.009) on days 2-10 postinoculation. The reduction in shedding of virus protein corresponded well with delayed onset of acute diarrhea (P < 0.02). Closer examination of tissue cross sections under electron microscopy revealed that the B. bifidum-ingested strain adhered to the epithelium of the small intestine. These results suggest that priming the intestine with B. bifidum is effective against experimental MRV challenge and confirmed the potential usefulness of this detector ELISA for studying the kinetics of group A rotavirus infection in animals and humans.

Sexual activity, contraception, and reproductive factors in predicting endometriosis.

To examine the belief that women with endometriosis have "voluntarily" delayed childbirth, the authors used a case-control approach to assess the relation between sexual, contraceptive, and reproductive factors and endometriosis. A total of 104 laparoscopically confirmed newly diagnosed cases of endometriosis were identified from a gynecologic specialty clinic in western New York state in 1987. Two control groups were used: 1) 100 friend controls, and 2) 98 medical controls. No differences were found between study groups on use of reliable birth control, use of birth control before a first pregnancy, age at first intercourse, frequency of intercourse, decisions to delay pregnancy, age at first pregnancy, or measures of body size. Cases were older than medical controls by about 1 year when they first began using birth control (19.8 vs. 18.6 years, p < 0.05). Cases were also 1 year older than friend controls when they began regular intercourse (20.9 vs. 19.5 years, p < 0.005) and at first marriage (22.8 vs. 21.7 years, p < 0.05). A larger percentage of cases than friend controls were never pregnant (p < 0.0001) and were more likely to have problems becoming pregnant (p < 0.0001). Results, overall, do not support simplistic assumptions that characterize endometriosis patients as career women who voluntarily delay pregnancy. Rather, the results point to a complex relation between endometriosis and reproductive, sexual activity, and fertility-related factors.

Effectiveness of Bifidobacterium bifidum in mediating the clinical course of murine rotavirus diarrhea.

Human Bifidobacterium sp strain bifidum (B. bifidum) was administered to BALB/c lactating mice (n = 58) and their litters (n = 327 pups) to evaluate the ingested strain's adherent properties and ability to inhibit murine rotavirus (MRV) infection. ELISA and anaerobic bacteriologic techniques were used to measure MRV shedding and colonization of Bifidobacterium in the small intestine. At 13-16 d gestation, pregnant dams (and their expected litters) were randomly assigned to one of four experimental groups: 1) normal controls; 2) B. bifidum-treated only; 3) MRV-infected only; and 4) B. bifidum-treated + MRV-infected dams and litters. During the acute phase of diarrhea, 80% of small-intestine cultures in B. bifidum-treated litters were positive for the ingested B. bifidum strain compared with 24% of fecal cultures. Examination of tissue cross sections under electron microscopy revealed the ingested B. bifidum strain survived passage through the upper gastrointestinal tract and adhered to the small-intestine epithelium. After the administration of the high dose of virus, diarrhea developed in all pups, but onset was significantly delayed in B. bifidum-treated + MRV-infected litters compared with litters infected with MRV only (p < 0.02). B. bifidum-treated+MRV-infected pups demonstrated a significant reduction in MRV shedding compared with litters challenged with MRV only at d 2 to 10 after inoculation (p < 0.009). More direct studies are needed to assess mechanisms by which this anaerobe can alter the course of MRV infection at the level of gut epithelium.

Occupational exposures associated with male breast cancer.

The role of occupational exposure to heat and electromagnetic fields was investigated in a case-control study of male breast cancer. Seventy-one cases reported to the New York State Tumor Registry between 1979 and 1988 were compared with 256 healthy male controls. Controls were frequency matched to cases by race, year of diagnosis, and age in 5-year intervals. Unconditional logistic regression modeling indicated that males with occupations that involved heat exposure had an elevated risk for the disease. The age- and county-adjusted odds ratio was 2.3 (95% confidence interval (CI) 0.95-5.3). Exposure to heat on the job could influence testicular function. No increase in disease risk was observed for males believed to have occupational exposure to electromagnetic fields (odds ratio = 0.7, 95% CI 0.3-1.9).

Effectiveness of Bifidobacterium bifidum in experimentally induced MRV infection: dietary implications in formulas for newborns.

The protective effect of a human strain of Bifidobacterium bifidum (B. bifidum) against murine Group A rotavirus (MRV) was examined in the intestines of BALB/c infected mice. In experiments designed to determine whether B. bifidum mediated MRV shedding during diarrheal disease, pregnant dams (and their expected litters) were randomly assigned to the following groups: 1. Mice infected with MRV alone; 2. B. bifidum treated + MRV infected mice; 3. B. bifidum treated controls; 4. Saline control animals. An enzyme-linked immunosorbent assay (ELISA) for the detection of group A rotavirus was used to measure virus protein. Treatment with B. bifidum significantly reduced shedding of MRV antigen (P < 0.009) days 2-10 post-inoculation. The reduction in shedding of virus protein corresponded well with delayed onset of acute diarrhea (P < 0.02). Closer examination of tissue cross-sections under electron microscopy revealed that the B. bifidum ingested strain adhered to the epithelium of the small intestine. In further experiments, adherent properties of the ingested strain were related to enhancement, although nonsignificant, in immunoglobulin secreting cell responses in Peyer's patch lymphocytes. These results suggest that priming the intestine with B. bifidum is effective against experimental MRV challenge. Closer examination of B. bifidum and related growth factors in suckling neonates on gut physiology and enhancement of local immune responses has potential dietary implications in formulas for newborns.

Use of city directories as a source of occupational data in a case-control study.

The association between occupational factors and male breast cancer was investigated in a population-based case-control study conducted in Western New York state. Since 9% of cases and controls were missing occupational information in the tumor registry (usual occupation) and screening clinic (type of work done) files, supplemental occupational data were collected from commercial city directories. Occupational data were located for 69% of participants via the city directory thereby reducing the missing occupational data to 3%. For individuals with occupational listings in both the original source document and the city directories, similar titles were found for 94% of cases. Factors to be considered in assessing the feasibility of directory usage include purpose of study, degree of directory coverage within the geographic area, gender of participants, and availability of personnel and resources. City directories are a valuable supplemental source of occupational data for hypothesis generating case-control studies or registry-based studies of men conducted in urban areas.

Endometriosis and body fat distribution.

OBJECTIVE: To examine the association of body fat distribution with risk of endometriosis in an effort to determine whether a specific somatotype is related to the disease. METHODS: We conducted a case-control study of 88 laparoscopically confirmed cases of endometriosis, identified in a specialty gynecologic practice in western New York, and 88 age-matched friend controls. Data were collected by standardized personal interview, and body measurements were taken in a standardized fashion by one interviewer. Risk of endometriosis associated with body fat distribution, as expressed by waist-to-hip and waist-to-thigh ratios, was assessed using logistic regression. RESULTS: For women under 30 years of age (45 cases, 46 controls), endometriosis was inversely related to both waist-to-hip ratio (odds ratio 6.18, 95% confidence interval [CI] 2.01-19.01) and waist-to-thigh ratio (odds ratio 3.64, 95% CI 1.23-10.78). This effect was not evident among women aged 30 years and older (43 cases, 42 controls). CONCLUSION: Our results suggest a specific somatotype with a predominance of peripheral body fat among women with endometriosis. This finding may provide information useful in both the diagnosis and understanding of the disease etiology.

Fat and calories in the epidemiology of colon cancer in western New York.

In this article, we contrast three models of macronutrients in the epidemiology of colon cancer. We then evaluate a dataset collected in Buffalo showing that the macronutrient model we use to guide our data analysis has a decisive bearing on the answers we obtain. We attempt to demonstrate that the method of statistical analysis we employ depends on the biologic-behavioral model that we assume and that, if we assume the wrong model, we may perform the wrong analysis and generate an answer that is wrong. We focus on dietary fat, because the intake of fat has received so much attention in the nutritional epidemiology of cancer. In addition, the intake of fat brings the issue of collinearity between a macronutrient and total caloric intake into focus and helps accentuate the contours of our debate.

Menstrual cycle characteristics and the risk of endometriosis.

The present study utilized a case-control design to assess the relation between menstrual cycle factors and risk of endometriosis in women age 19-45 years. From a gynecologic specialty clinic in Western New York in 1987, we identified 104 laparoscopically confirmed cases of endometriosis. We used two control groups: (1) 100 friend controls (friends of cases), and (2) 98 medical controls (patients from the same medical practice with conditions other than endometriosis). Controls were frequency matched to cases by age. Because crude odds ratios (ORs), stratified by age (< 30 vs > or = 30 years), revealed effect modification by age, we performed all analyses by age group. We used logistic regression to calculate ORs and 95% confidence intervals (CIs), controlling for pregnancy, religion, and body mass index. Among women under age 30, using friend controls, we observed elevated risks for menstrual flow > or = 6 days per month (OR = 2.5, 95% CI = 1.1-5.9), heavy flow (OR = 2.5, 95% CI = 1.1-6.3), severe cramps (OR = 2.5, 95% CI = 1.2-6.0), increasing symptoms (OR = 6.6, 95% CI = 2.6-16.5), and tampon use > or = 14 years (OR = 3.6, 95% CI = 1.04-13.5). Risks were also elevated for women age 30 and over, but not to the same degree as among younger women.(ABSTRACT TRUNCATED AT 250 WORDS)

Lag time between stress events and risk of recurrent episodes of inflammatory bowel disease.

We followed a cohort of 124 subjects with a history of inflammatory bowel disease to ascertain risk estimates for clinically active disease associated with exposure to recent stress events. We calculated risk estimates for three lag models (-1, 0, + 1 month). The data indicated a strong association between stress exposures and new clinical episodes of disease (RR = 2.9, 95% Cl: 2.0-4.1), most apparent in the immediate period (lag = 0). Risk estimates were also elevated for extended episodes of disease in subjects under stress compared with unexposed subjects. These results underscore the importance of monitoring stress exposures in prevention and treatment of recurrent disease.

Rural medicine and the closed society. Pregnancy outcomes among Amish and non-Amish women.

A rural family practitioner may be responsible for the general medical and obstetric needs of a closed population such as the Old Order Amish. Until recently, the Amish in southern New York State have preferred to receive obstetric care in the home from traditional Amish midwives. Acceptance of prenatal care and hospital deliveries by rural physicians appears to be increasingly frequent among Amish primiparas in southern New York State, while non-Amish in the area have been seeking these services for decades regardless of parity. This retrospective chart review examines first pregnancy outcomes of Amish (N = 39) and non-Amish (N = 145) women who delivered their babies at a rural hospital in southern New York State during a four-year period. Little difference was found between the two groups of women regarding the overall good health of their first babies. In the Amish population there was less variability in maternal age, season in which the birth occurred, labor duration, and birth weight of babies. The Amish had their first child an average of one year later than the non-Amish. While research on a larger sample will be necessary to fully explore Amish vs non-Amish variances, this study demonstrates the effect that traditions and customs of a closed society such as the Amish may have on obstetric practice.

Predictors of attempting and succeeding at smoking cessation.

This paper presents results of a prospective study which examined factors influencing self-initiated smoking behavior change in a cohort of smokers followed over 17 months. Employees of a cancer hospital and research center were surveyed about smoking habits, health status, attitudes about smoking and social-environmental factors. Seventeen months later, employees identified as smokers were resurveyed about their current smoking status, recent attempts at cessation and use of cessation aids in these attempts. Overall, 47% of subjects had not tried to stop smoking (non-stoppers, NS), 38% had attempted to quit but returned to smoking (recidivists, R) and 15% had successfully quit (SQ). Predictors of attempting cessation (R and SQ versus NS) included smoking fewer cigarettes daily, starting smoking at a later age, previous attempts at quitting, lower nicotine dependence, greater pressure to stop smoking and an expectation to quit in the near future. Amount smoked daily was the strongest predictor of successful quitting (SQ versus R). Findings from this study suggest intention to stop smoking is the most important factor differentiating smokers who attempt cessation from those who do not. Strength of smoking habit appears to be the strongest factor associated with successful quitting.

Relevance of major stress events as an indicator of disease activity prevalence in inflammatory bowel disease.

The impact of psychological stress in recurrence of inflammatory bowel disease (IBD) is unclear. Why some patients with ulcerative colitis (UC) or Crohn's disease (CD) have unrelenting relapses whereas other IBD patients experience long periods of quiescent disease remains an enigma. The authors examined the risk of exposure to major stress events in clinical episodes of IBD. They followed up on 124 persons in a prospective study that monitored behavioral and biological characteristics for a period of 6 months. Stress-exposed subjects demonstrated increased risk of clinical episodes of disease when compared with unexposed subjects (RR = 2.6, 95% CI: 1.3-4.9). Elevated effect measures were highest for the domain of health-related stress (RR = 3.8, 95% CI: 1.5-9.9). In the multiple regression analysis, major stress events remained the most significant indicator of disease activity in the presence of the covariables considered. Only 7% of the variation in disease activity was uniquely attributed to stress. Baseline activity was the other notable indicator of subsequent disease activity in the study sample. All variables considered together explained 52% of the variance observed and implicated factors of potential clinical importance in monitoring recurrence of the disease.

Cigarette smoking and risk of clinical relapse in patients with Crohn's disease.

Risk of clinical relapse among cigarette smokers and nonsmokers was examined in a cohort of 74 adult Crohn's disease (CD) patients who were identified and followed at monthly intervals for six months. We measured clinical activity by a weighted symptom index used previously. Relapse at any point during the study was defined by the index score exceeding 150. Approximately 50% of nonsmokers experienced clinical relapse during the study period. Current smokers experienced a relapse risk 1.6 times that of nonsmokers (P less than .01). The risk estimates correspond to mean overall clinical activity scores of 142 +/- 34 for smokers compared to 119 +/- 26 for nonsmokers. Adjustment for confounding effects did not substantially alter the association shown between cigarette use and clinical relapse. We observed no increase in the likelihood of relapse among former smokers. The statistically significant finding that current smoking increases the risk of relapse for CD patients is of clinical importance, given the high prevalence of smoking (42%) among CD patients in this sample.

Vasoactive intestinal peptide as a laboratory supplement to clinical activity index in inflammatory bowel disease.

Circulating levels of vasoactive intestinal peptide (VIP) in plasma were measured in gauging activity in inflammatory bowel disease (IBD). One hundred-fifteen adult IBD patients were studied cross-sectionally and prospectively, 48 with ulcerative colitis (UC) and 67 with Crohn's disease (CD). Sequential samples of plasma were assayed for VIP by specific radioimmunoassay. Sixty males and 55 females, ranging in age from 22 to 76 years were studied over six months. The results revealed a strong, positive association between VIP levels and clinical activity, both at baseline (r = 0.38, P less than 0.001) and follow-up (r = .41, P less than 0.001). The ability of the VIP immunoassay to gauge clinical activity was also evaluated where VIP concentrations above 30 pg/ml were defined as abnormal. At baseline, sensitivity (specificity) was found to be 81% (55%). The predictive value of a positive (negative) test was 57% (80%). These estimates did not differ at follow-up. Examination of paired plasma samples from intermittently active patients revealed nearly twofold increases (P less than 0.05) in VIP concentration during active periods of disease. The data suggest that plasma VIP levels may be a valuable laboratory parameter in gauging activity in inflammatory bowel disease.

Validity and reliability of the interval scale of anxiety response.

The Interval Scale of Anxiety Response (ISAR) is shown to be a valid and reliable instrument for measuring situation dental anxiety in adults. The ISAR demonstrates differences that are known or expected between various population subgroups. Thus, significantly higher scores, indicating greater levels of anxiety, are reported by women compared with men; by hospital clinic patients compared with private practice patients; by occasional compared with regular users of dental care; by those with lower educational levels; and by those patients undergoing exodontia compared with patients having other dental procedures. Younger adults also report significantly higher anxiety scores during treatment than older adults. The ISAR is also significantly associated with other measures of anxiety and pain, and with a measure of dentistrated difficulty of extraction. Reliability is assessed favorably and present-time administration is found to improve ISAR accuracy over its retrospective use.