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.

Consumption of contaminated sport fish from Lake Ontario and time-to-pregnancy. New York State Angler Cohort.

Sport fish from the Great Lakes are contaminated with halogenated organics, heavy metals, and pesticides, thus serving as a route of exposure for fish-consuming populations. These contaminants are recognized reproductive toxicants in animals; few human studies are available. The purpose of this study was to assess consumption of contaminated fish in relation to time-to-pregnancy (TTP) among women in the New York State Angler Cohort. In 1993, structured telephone interviews were conducted with 2,445 of 2,977 (82%) female cohort members aged 18-40 years who stated upon enrollment in the cohort in 1991 that they were considering pregnancy over the next 3 years. Among the 1,234 women who reported being pregnant, 874 (71%) had a known TTP and comprise the study sample. After descriptive analyses, log transformations of the number of years of fish consumption (duration) and TTP were performed and entered into multiple regression models that also included other covariates. Duration of fish consumption and maternal age accounted for only a small percentage of the explained variance in TTP (R2 = 0.005), even after the analysis was restricted to women who reported eating fish (R2 = 0.006). All beta coefficients were positive. These preliminary findings do not support an adverse effect of contaminated fish consumption on TTP.

Consumption of PCB-contaminated freshwater fish and shortened menstrual cycle length.

Highly contaminated Lake Ontario sport fish represent an important human dietary exposure to polychlorinated biphenyls (PCBs) and other toxic contaminants that may disrupt endocrine pathways. New York State Angler Cohort women interviewed by telephone in 1993 provided menstrual cycle length (n = 2,223). Fish consumption at cohort enrollment in 1991 was categorized by duration and frequency and was used to calculate a PCB exposure index. Multiple regression analyses identified significant cycle length reductions with consumption of more than one fish meal per month (1.11 days) and moderate/high estimated PCB index (-1.03 days). Women who consumed contaminated fish for 7 years or more also had shorter cycles (-0.63 days).

Gender differences in the relation between depressive symptoms and alcohol problems: a longitudinal perspective.

Longitudinal relations between depressive symptoms and alcohol problems have been examined infrequently in community-based studies, and gender-specific findings to date appear to be inconclusive. Study hypotheses were that depressive symptoms predicted subsequent alcohol problems for females, whereas alcohol problems predicted subsequent depressive symptoms for males. The authors examined these relations in a random sample of household adults (aged 19 years or more) from Erie County, New York, assessed in 1986, 1989, and 1993 (n = 1,306). Measures of alcohol problems (in the previous year) incorporated an alcohol abuse/dependence diagnosis and a heavy alcohol use index. The Center for Epidemiologic Studies Depression Scale was used to assess depressive symptoms over a 1-month time frame. Comprehensive logistic regression models incorporated prior depressive symptoms, prior alcohol problems and sociodemographic variables (age, race, education, marital status, employment, total family income, and number of children living at home). For females, depressive symptoms predicted subsequent alcohol problems over 3 years (odds ratio = 3.04, 95% confidence interval 1.35-6.80, p < 0.01) and 4 years (odds ratio = 2.42, 95% confidence interval 1.14-5.12, p < 0.05), but not for 7 years. There was no evidence to support the hypothesis for males. This study clarifies and extends prior investigations of relations between these two prevalent mental health problems in a community-based sample.

Overcoming resistance to exposure in panic disorder with agoraphobia.

The issue of panic disorder resistant to treatment (whether pharmacological or psychological) has attracted little research attention, despite its clinical frequency and importance. The aim of this study was to compare three treatment modalities, namely exposure alone (E), exposure associated with imipramine (EI) and cognitive therapy supplementing exposure (EC), in a sample of 21 patients with DSM-IV panic disorder and agoraphobia, who failed to respond to a first standard course of individual behavioural treatment based on exposure in vivo. Treatments were administered according to a cross-over, controlled design (E-EI-EC, EI-EC-E, EC-E-EI). Twelve of the 21 patients achieved remission (panic-free status) during the trial. In 8 cases this occurred after exposure alone (E) and in two cases each after the other treatments (EI and EC). The results revealed a significant effect of the factor time on a number of variables, and the superiority of exposure alone compared to other treatment modalities with regard to some variables. These findings suggest that long-term behavioural treatment based on exposure may be necessary in some patients, and may induce clinical remission. However, patients who do not respond to exposure show poor tolerance of and compliance with pharmacological treatment, and are unlikely to achieve remission with imipramine or cognitive therapy, even though this may occur in individual cases.

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.

Exercise, occupational activity, and risk of endometrial cancer.

We conducted a case-control study in western New York state among 232 women with newly-diagnosed endometrial cancer and 631 controls selected from the community. Physical activity was measured by participation in vigorous exercise and walking at four time periods: at age 16, and at 20, 10, and 2 years before the interview and by occupational activity based on a detailed lifetime history. Women who did a moderate amount of vigorous exercise at age 16 and at 20 years before the interview were at reduced risk as compared with those who reported no activity, with odds ratios (OR) (95% confidence intervals) of 0.51 (0.31-0.83) and 0.50 (0.29-0.89), respectively. However, there was no evidence of declining risk with greater amount of activity. At later times, 10 years and 2 years before the interview, being in the highest group with regard to vigorous activity was associated with a slightly but nor significant lower risk as compared with women who reported no activity; the adjusted OR were 0.72 (0.43-1.19) and 0.67 (0.42-1.09), respectively. Being in the highest category of miles walked at age 16 (i.e., > or = 15 miles per week) was associated with a slightly reduced risk as compared with not walking at all (OR 0.64 (0.26-1.16)), whereas the number of miles walked at other times was not related to reduced risk. Occupational physical activity was not related to the risk of endometrial cancer. Overall, these results indicate that physical activity at levels prevalent in this population has at most a modest relationship to reduced risk of endometrial cancer.

Diet and alcohol consumption and lung cancer risk in the New York State Cohort (United States)

The relationship between diet and alcohol and lung cancer was evaluated among participants of the New York State Cohort (United States), comprising 27,544 men (395 cases) and 20,456 women (130 cases) who completed a brief mailed questionnaire in 1980. Participants were followed up through 1987 with the assistance of the New York State Department of Health's Vital Statistics Section and Cancer Registry. Among men, inverse relationships with vitamin C, folate, and carotenoids, and positive associations with total fat, monounsaturated and saturated fat were observed after adjusting for age, education, cigarettes/day, years smoking, and total energy intake. The relationships observed with folate and saturated fat were stronger for heavy smokers. Also, the effect of folate, total fat, and monounsaturated fat seemed to be limited to squamous cell carcinomas. We found no indication that cholesterol or polyunsaturated fat was associated with lung cancer. Diet did not appear to exert a major role on lung cancer risk among women. Although diet modification should never be considered a substitute for smoking cessation, its role as an additional strategy in lung cancer prevention deserves attention.

Risk factors and long-term outcome in pituitary-dependent Cushing's disease.

Although transphenoidal pituitary microsurgery has become the treatment of choice in Cushing's disease, other procedures, such as bilateral adrenalectomy and pituitary irradiation, are currently in use in its management. Indeed, no treatment has proven to be fully satisfactory for this condition. The rates of cure and recurrence after pituitary surgery or irradiation and the incidence of Nelson's syndrome after bilateral adrenalectomy are still open issues. A population of 162 patients with pituitary-dependent Cushing's disease was studied at 1 institution and had a follow-up of at least 2 yr after treatment (median, 7 yr). Patients were divided in subgroups according to the type of treatment: transsphenoidal pituitary microsurgery, bilateral adrenalectomy, or pituitary irradiation. Survival analysis was employed to characterize the outcome of treatment in each subgroup. Predictive factors for success of pituitary surgery were also evaluated. The estimated cumulative percentage of patients remaining in remission after successful pituitary surgery (n = 79) was 93.7% after 2 yr, 80.6% after 5 yr, 78.5% after 7 yr, and 74.1% after 10 yr. Of 8 risk factors examined, the following attained statistical significance: age, clinical severity, presence of major depression, pre- and posttreatment urinary cortisol levels, and posttreatment ACTH level. Pituitary surgery was successful in 79 of 103 patients (76.7%). Surgical failure was significantly associated with lack of pituitary adenoma and the clinical severity and presence of major depression. Of patients treated by bilateral adrenalectomy (n = 63), the estimated cumulative percentage remaining free of Nelson's syndrome was 87.1% after 2 yr, 79.3% after 7 yr, and 71.2% after 10 yr. The occurrence of Nelson's syndrome was significantly related to the pretreatment urinary cortisol level and the presence of pituitary adenoma at previous pituitary surgery. After cure by pituitary irradiation (n = 23), the estimated cumulative percentage of patients remaining in remission was 100% after 2 yr, 81.8% after 5 yr, 71.6% after 7 yr, and 65.1% after 10 yr. Previous pituitary surgery, although unsuccessful, appeared to be a protective factor for relapse. The results indicate that relapse after cure by either pituitary surgery or irradiation is a considerable clinical problem that increases over time. Our findings ascribe new importance to the clinical presentation of patients and indicate subgroups that are at high risk for relapse after pituitary surgery or irradiation and for developing Nelson's syndrome after bilateral adrenalectomy.

Four-year outcome for cognitive behavioral treatment of residual symptoms in major depression.

OBJECTIVE: The authors' goal was to determine whether cognitive behavioral treatment of residual symptoms of depression might have a significant effect on relapse rate. METHOD: In an earlier study, 40 patients with primary major depressive disorder who had been successfully treated with antidepressant drugs were randomly assigned to either cognitive behavioral treatment of residual symptoms or standard clinical management. In both types of treatment, antidepressant drugs were gradually tapered and discontinued. In this study, a 4-year follow-up assessment was performed. RESULTS: Cognitive behavioral treatment resulted in a substantially lower relapse rate (35%) than did clinical management (70%). CONCLUSIONS: Cognitive behavioral treatment of residual symptoms reduces the risk of relapse in depressed patients, probably by affecting the progression of residual symptoms to prodromes of relapse.

The New York Angler Cohort Study: exposure characterization and reproductive and developmental health.

The New York State Angler Study will evaluate the association between past and current consumption of contaminated fish from Lake Ontario and both short- and long-term health effects in a population-based cohort. It will measure fish consumption and reproductive and developmental health among 10,518 male anglers and 6,651 of their wives or partners, as well as among 913 female anglers. To characterize exposure among subgroups of the cohort, further analytical methods were developed and implemented to measure specific polychlorinated biphenyls (PCB) congeners, methylmercury, and other substances in biological samples. Exposure assessment has been completed for a stratified random sample of 321 anglers. In addition, analyses for 79 congeners of PCBs are complete for 177 anglers. A special study of duck and turtle consumers currently is underway. Telephone interviews have been completed with 2,454 of the 2,999 women who planned a pregnancy between 1991 and 1994. The entire cohort of male anglers, partners of male anglers, and female anglers has been submitted for matching with the New York State live birth and fetal death registries to obtain lifetime reproductive histories. A medical record abstraction study will assess perinatal and developmental outcomes among the 3,442 births that occurred between 1986 and 1991. Finally, a study of breast milk from currently lactating women is underway, and 215 breast milk samples have been collected from the planned pregnancy subcohort. Progress on each of the study components is discussed herein.

A case-control study to examine the influence of maternal perinatal behaviors on the incidence of Crohn's disease.

This case-control study, which examines maternal perinatal characteristics and behaviors during pregnancy, was an initial step to determine whether an association exists between breast feeding, oral contraceptive use, smoking habits during pregnancy, and the incidence of Crohn's disease. The population studied was mothers whose children were diagnosed with Crohn's disease before the age of 22. Population controls were selected by each case mother, who solicited two friends or neighbors with a child of similar age. Case mothers differed significantly on the variables of allergies (p = .05) and family history of inflammatory bowel disease (p = .001). No significant differences were found regarding feeding, oral contraceptives, or smoking. Using a forward step-wise logistic regression method, only family history remained in the equation.

Trichomonas vaginalis and cervical cancer. A prospective study in China.

The relationship between Trichomonas vaginalis infection and cervical cancer was investigated prospectively in a cohort of 16,797 women aged 25 years or more who were followed from 1974 to 1985 within the framework of a cervical screening program in Jingan, China. Personal interviews were conducted by trained interviewers when the women first entered the screening program. At initial screening, 421 (2.51%) women had a positive cytologic diagnosis of T. vaginalis infection. Ninety-nine incident cases of pathologically confirmed squamous cell carcinoma were identified from the cohort, with a total of 140,018 person-years of observation. T. vaginalis infection was found to contribute to the risk of cervical cancer, as determined by crude estimates and after adjustment for potential confounding effects. In a multiple proportional hazards model, the relative risk for cervical cancer was 3.3 (95% confidence interval: 1.5 to 7.4) among women with T. vaginalis infection. Furthermore, in the multivariate analysis, increased risk of cervical cancer was associated with the following factors: number of extramarital sexual partners of both the subjects and their spouses, cigarette smoking, and irregular menstruation. Having a large number of negative Pap smears was associated with lower risk. This study suggests that there might be an association between T. vaginalis infection and the risk of cervical cancer, but only 4 to 5% of cervical cancer in Chinese women may be attributable to T. vaginalis infection.

Consumption of PCB-contaminated sport fish and risk of spontaneous fetal death.

Spontaneous fetal death has been observed among various mammalian species after exposure to polychlorinated biphenyls (PCBs). Our exposure-based cohort study assessed the relationship between consumption of PCB-contaminated Lake Ontario sport fish and spontaneous fetal death using 1820 multigravid fertile women from the 1990-1991 New York State Angler Cohort Study. Fish consumption data were obtained from food frequency questionnaires and history of spontaneous fetal death from live birth certificates. Analyses were stratified by number of prior pregnancies and controlled for smoking and maternal age. No significant increases in risk for fetal death were observed across four measures of exposure: a lifetime estimate of PCB exposure based on species-specific PCB levels; the number of years of fish consumption; kilograms of sport fish consumed in 1990-1991; and a lifetime estimate of kilograms eaten. A slight risk reduction was seen for women with two prior pregnancies at the highest level of PCB exposure (odds ratio = 0.36; 95% CI, 0.14-0.92) and for women with three or more prior pregnancies with increasing years of fish consumption (odds ratio = 0.97; 95% CI, 0.94-0.99). These findings suggest that consumption of PCB-contaminated sport fish does not increase the risk of spontaneous fetal death.

Occupational exposure to extreme temperature and risk of testicular cancer.

A study of 250 patients with pathologically confirmed testicular cancer diagnosed between January 1977 and June 1980 and 250 population controls matched for age and residence was carried out to investigate risk factors for testicular cancer. This paper reports results of risk associated with occupational exposure to extreme (< or = 60 degrees F or > or = 80 degrees F), high (> or = 80 degrees F), and low (< or = 60 degrees F) temperature. Interviews of approximately 1.5 h duration were conducted by trained male interviewers, using a standardized interview schedule. Mantel-Haenszel methods and logistic regression models were employed to estimate these temperature effects on risk of testicular cancer. The estimated adjusted odds ratios of testicular cancer, when 16 potential confounders were controlled for, were 1.71 (95% Cl: 1.13-2.60) for occupational exposure to extreme temperatures; 1.70 (1.04-2.78) for low temperature; and 1.20 (0.80-1.80) for high temperature. The findings suggest that occupational exposure to extreme, low, and high temperature may increase risk of testicular cancer, independent of other potential risk factors.

Long-term effects of behavioural treatment for panic disorder with agoraphobia.

BACKGROUND: There are few long-term follow-up studies of panic disorder treatments, particularly when patients have been treated by behavioural methods only and have recovered. METHOD: 110 consecutive patients satisfying the DSM-III-R criteria for panic disorder with agoraphobia were treated in an out-patient clinic with behavioural methods based on exposure. After 12 sessions of psychotherapy, 81 patients became panic-free. A 2-9 year follow-up was available. Survival analysis was employed to characterise the clinical course of patients. Regular assessments by a clinical psychologist were based on the Clinical Interview for Depression. RESULTS: The estimated cumulative percentage of patients remaining in remission was 96.1% for at least two years, 77.6% for at least five years, and 67.4% for at least seven years. These outcomes greatly improved in the absence of a personality disorder or residual agoraphobia after treatment. CONCLUSIONS: The findings suggest that, even though one patient in four is unable to complete treatment or does not benefit sufficiently from it, exposure treatment can provide lasting relief for the majority of patients. Disappearance of residual and subclinical agoraphobic avoidance, and not simply of panic attacks, should be the aim of exposure therapy.

Body mass index, weight gain, and risk of endometrial cancer.

Excess weight near the time of diagnosis is a well-established risk factor for endometrial cancer; less is known about the influence of weight at earlier periods of a woman's life or weight gain in adulthood. In a case-control study in western New York State, interviews were conducted with 232 incident endometrial cancer cases, diagnosed between 1986 and 1991, and 631 community controls. Body mass index at 16 years of age and 20, 10, and 2 years before interview and changes in body mass index between these time periods were examined. While being relatively heavy at 16 years of age was associated with slightly increased risk [adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 0.84-1.96], large gains over the entire period from 16 years of age to 2 years ago (OR = 3.45, CI = 2.13-5.57) and high body mass index close to the time of diagnosis (OR = 3.21, CI = 2.01-5.15) were associated with greater risk. Differences in mean body mass index between cases and controls increased over time.

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.