Basal Diet Fed to Recipient Mice Was the Driving Factor for Colitis and Colon Tumorigenesis, despite Fecal Microbiota Transfer from Mice with Severe or Mild Disease.

Consumption of the total Western diet (TWD) in mice has been shown to increase gut inflammation, promote colon tumorigenesis, and alter fecal microbiome composition when compared to mice fed a healthy diet, i.e., AIN93G (AIN). However, it is unclear whether the gut microbiome contributes directly to colitis-associated CRC in this model. The objective of this study was to determine whether dynamic fecal microbiota transfer (FMT) from donor mice fed either the AIN basal diet or the TWD would alter colitis symptoms or colitis-associated CRC in recipient mice, which were fed either the AIN diet or the TWD, using a 2 × 2 factorial experiment design. Time-matched FMT from the donor mice fed the TWD did not significantly enhance symptoms of colitis, colon epithelial inflammation, mucosal injury, or colon tumor burden in the recipient mice fed the AIN diet. Conversely, FMT from the AIN-fed donors did not impart a protective effect on the recipient mice fed the TWD. Likewise, the composition of fecal microbiomes of the recipient mice was also affected to a much greater extent by the diet they consumed than by the source of FMT. In summary, FMT from the donor mice fed either basal diet with differing colitis or tumor outcomes did not shift colitis symptoms or colon tumorigenesis in the recipient mice, regardless of the basal diet they consumed. These observations suggest that the gut microbiome may not contribute directly to the development of disease in this animal model.

Immune responses in tuberculosis: antibodies and CD4-CD8 lymphocytes with vascular adhesion molecules and cytokines (chemokines) cause a rapid antigen-specific cell infiltration at sites of bacillus Calmette-Guérin reinfection.

Rabbit primary dermal bacillus Calmette-Guérin (BCG) lesions were compared with reinfection BCG lesions in order to gain insight into how immune responses protect against clinical tuberculosis. As early as 3 hr, a marked infiltration of macrophages and lymphocytes occurred in the reinfection group, while very little cell infiltration occurred in the primary group. It seems that only an antigen-antibody reaction could produce such an immediate pronounced antigen-specific chemotactic effect, because very few lymphocytes are normally present in the skin. Therefore, antibodies hasten the accumulation of an expanded antigen-specific T-lymphocyte population (memory cells) at sites of bacillary lodgement. By 1-2 days, the primary and reinfection BCG lesions differed 400- to 500-fold in size. By 4-5 days, the size of the reinfection lesions had declined, while the size of the primary lesions had increased, so that, grossly, both types of lesion were similar. At 8 days in reinfection lesions and at 12 days in primary lesions, small secondary peaks in size occurred, which were probably caused by cell-mediated immune responses. In rabbits with primary BCG lesions, skin tests with Old Tuberculin were positive at 9 days, accompanied by a rise in the levels of antibodies to the secreted antigen, phosphate-specific transport protein 1, but the levels of antibodies to the constitutive antigens, purified protein derivative and heat-shock protein 65, did not increase appreciably until some time after 23 days. In tissue sections of reinfection BCG lesions, the percentage of mononuclear cells labelled, by in situ hybridization techniques, for the mRNA of monocyte chemoattractant protein 1 (MCP-1), a chemokine, peaked at 3 hr and then was down-regulated, whereas in primary lesions, this percentage was down-regulated only after 2 days. [The percentage in the tissue sections for the mRNAs of interleukins 1beta and 8, as well as the proteins of MCP-1 and tumor necrosis factor alpha (TNF-alpha), followed a somewhat similar time-course to that of MCP-1 mRNA.] A high percentage of mononuclear cells containing the MCP-1 mRNA 'factory' would favour enlargement of the lesions and a low percentage would favour their regression. At 5 days, the percentage of CD4 and CD8 lymphocytes, stained by immunohistochemical techniques, and the amount of microvasculature stained similarly for vascular cell adhesion molecule 1 were higher in the reinfection group, indicating that prior immunization caused a more rapid (antigen-dependent) up-regulation of these factors. Tuberculin reactions resembled early reinfection BCG lesions in almost every factor evaluated herein. In brief, the production of chemokines began soon after BCG reinfection, peaked within a few hours and was markedly down-regulated by 24 hr, a time at which the lesions of reinfection were of maximal size. Therefore, the amount of cell infiltration was tightly controlled, probably by the variety of mechanisms listed herein.

Epidemiology of Helicobacter pylori in chronic haemodialysis patients using the new RIBA H. pylori SIA.

BACKGROUND: There are few data concerning the epidemiology of H. pylori in patients on chronic haemodialysis (HD) treatment. These surveys concerned small populations and were made with ELISA technique. However, ELISA-based assays do not differentiate between strains of H. pylori that are associated with ulcers. Recent literature reports that formation of ulcers correlates strongly with the expression of cytotoxin-associated protein (CagA) and vacuolating cytotoxin (VacA) of H. pylori. METHODS: A novel serological test (RIBA H. pylori strip immunoblot assay (SIA)) has been recently introduced, it uses the H. pylori lysate (Lys) along with two additional purified recombinant antigens derived from CagA and VacA of H. pylori. AIM: To study the epidemiology of H. pylori using RIBA H. pylori SIA among chronic HD patients and blood donors as a control group. In addition, the activity of H. pylori was analysed by immunoblot technique in a group of patients with documented ulcers and normal renal function. RESULTS: The prevalence of antibody towards H. pylori among HD patients, blood donors, and patients with documented ulcers was 56% (127/228), 53% (84/158), and 100%, (21/21) respectively; the difference was significant (P=0.0001). The frequency of anti-H. pylori-positive individuals was significantly higher in patients with documented ulcers than HD patients and blood donors, 21/21 (100%) vs 211/386 (55%), P=0.0001. The frequency of antibody to H. pylori in the HD population was significantly associated with race (P= 0.005); no relationship between anti-H. pylori antibody and numerous demographic, biochemical, and clinical features of patients was seen. The frequency of antibodies against virulent strains of H. pylori in HD patients and blood donors with H. pylori was 60% (76/127) and 61% (51/84) respectively; it was 86% (18/21) among individuals with documented ulcers. No significant difference among these three groups occurred. CONCLUSIONS: The frequency of antibody towards H. pylori by RIBA H. pylori SIA was high both in HD patients and blood donors; patients with documented ulcers and normal renal function had significantly higher frequency of anti-H. pylori antibody. The anti-H. pylori antibody rate among HD patients was strongly associated with race. The prevalence of antibody against virulent strains of H. pylori did not change among HD patients and control groups. Studies in large cohorts of HD patients with documented peptic ulcer disease are in progress.

Pulmonary bovine-type tuberculosis in rabbits: bacillary virulence, inhaled dose effects, tuberculin sensitivity, and Mycobacterium vaccae immunotherapy.

This report elucidates four aspects of the immunology of pulmonary tuberculosis produced in rabbits: (i) the virulence of bovine-type tubercle bacilli, strain Ravenel S, (ii) systemic factors influencing the generation of visible primary pulmonary tubercles, (iii) differences in tuberculin sensitivity of rabbits and humans, and (iv) the effect of Mycobacterium vaccae immunotherapy on cavitary tuberculosis. Laboratory strain Ravenel S (ATCC 35720) was not fully virulent. Fully virulent strains produce one visible primary pulmonary tubercle for each three bacillary units inhaled. Strain ATCC 35720 produced one such tubercle for each 18 to 107 bacillary units inhaled, indicating that its virulence was reduced by 6- to 36-fold. When a low dose of this Ravenel S strain was inhaled, the host resistance (measured by the number of inhaled bacilli needed to generate one visible primary pulmonary tubercle) was increased at least 3.5-fold compared to the host resistance when a high dose was inhaled. Rabbits and humans differ in the degree and in the maintenance of their dermal sensitivities to tuberculin. Compared to rabbits, humans are 100 times more sensitive to tuberculin. Also, at 33 weeks rabbits with well-controlled cavitary tuberculosis usually showed a decrease in their tuberculin reactions of about 50% from peak values, whereas humans with such well-controlled tuberculosis are thought to maintain strong reactions for many years. These species differences may be due to desensitization to group II mycobacterial antigens in the rabbits because they have a different diet and a different type of digestive tract. M. vaccae immunotherapy of rabbits with cavitary tuberculosis produced no statistically significant effects. Experiments with many more rabbits would be required to prove whether or not such immunotherapy is beneficial.

Possible antioxidant effect of vitamin A supplementation in premature infants.

BACKGROUND: Increased lipid peroxidation caused by oxygen free radicals is thought to be one of the common pathogenetic mechanisms for the so-called oxygen radical diseases of prematurity. Since in vitro studies have shown that various forms of vitamin A can exert antioxidant effects that are more potent than those of vitamin E (treatment with which has been ineffective in these diseases), the purpose of this prospective, controlled study was to determine whether administration of supplemental vitamin A to premature infants deficient in this vitamin would have an antioxidant effect in vivo. METHODS: Fourteen infants (1181 +/- 35 g; gestational age 29 +/- 0.04 weeks) with a serum retinol concentration at 7 +/- 2 days of age in the deficient range, lower than 0.7 mumol/l (< 20 micrograms/dl), were enrolled in the study. Infants were randomized to receive the standard amount of vitamin A or standard plus supplemental (2.6 mumol/l [2500 IU] orally each day) vitamin A, beginning at 1 week of age. Antioxidant effects of supplementation were assessed by a decrease in lipid peroxidation, quantified by the ethane content of expired air. RESULTS: Three weeks after study enrollment, total daily vitamin A intake in the infants receiving supplements was 4.565 +/- 0.236 mumol (4354 +/- 225 IU) versus 1.879 +/- 0.317 mumol/l (1792 +/- 302 IU) in infants receiving standard amounts of the vitamin. In spite of the difference in intake of vitamin A, 3 weeks after study enrollment, serum retinol concentrations did not differ between the infants given supplements and those receiving standard amounts of vitamin A, 0.70 +/- 0.21 versus 0.66 +/- 0.07 mumol/l (20 +/- 6 micrograms/dl versus 19 +/- 2 micrograms/dl, respectively). In the infants receiving supplemental vitamin A, breath ethane values declined from baseline values. There was an inverse correlation between the number of weeks of supplementation and breath ethane values, whereas there was no significant correlation between the duration of the study and breath ethane values in the infants not given supplements. CONCLUSIONS: Our data suggest that supplementation with vitamin A in a small group of vitamin A-deficient preterm infants was associated with an antioxidant effect. Although no immediate clinical benefits were associated with supplementation, the data provide the rationale for future investigations of possible antioxidant effects of (larger amounts?) of vitamin A in higher risk premature infants born with subnormal serum retinol concentrations.

Prooxidant effects of maternal smoking and formula in newborn infants.

BACKGROUND: The purpose of this study was to use the breath ethane test to determine if either maternal cigarette smoking, formula, and/or deficiency of the antioxidant nutrients vitamins A and E was associated with oxidant stress in newborn infants. The rationale for this study was: (1) our observation that cigarette smoking was a source of oxidant stress in pregnant women, suggesting that it could be a source of oxidant stress for infants exposed in utero; (2) formula was predicted to be prooxidant compared to colostrum, which contains several compounds with antioxidant activity in vitro; and (3) deficiencies of vitamins A and E have been shown to promote oxidant stress in experimental animals. METHODS: Breath ethane, a volatile alkane produced by peroxide of n-3 fatty acids, was utilized as an index of oxidant stress status. Forty-five healthy full-term infants of the women mentioned above were studied at 18-24 h of age, after four to six feedings of breast milk (colostrum) or caseinbased infant formula. Relationships between infant breath ethane, maternal smoking, mode of infant nutrition, and serum concentrations of the antioxidant vitamins A and E of infants were examined. RESULTS: The breath ethane of the entire group of infants whose mothers smoked (n = 19) was increased compared to values of infants whose mothers did not smoke (n = 26): 97 +/- 16 versus 43 +/- 9 pmol/kg/min, p < 0.03. When infants of mothers who smoked were eliminated from the analysis in order to study effects of nutrition alone, formula appeared to be prooxidant compared to breast milk. Breath ethane of formula-fed infants (n = 16) was 62 +/- 13 versus 13 +/- 4 pmol/kg/min for breast-fed infants (n = 10), p < 0.04. For the group as a whole, there was no correlation between infant breath ethane and serum concentrations of vitamins A and E. CONCLUSIONS: Exposure to maternal smoking in utero is prooxidant in newborn infants. Formula also has a prooxidant effect compared to colostrum in newborn infants not exposed to maternal smoking in utero. Further investigations will be necessary to explore the clinical consequences of these observations.

Types and frequency of child maltreatment by family foster care providers in an urban population.

Types and frequency of child abuse and neglect reports in family foster care in Baltimore, Maryland as compared to reports among nonfoster families are reported. Data on maltreatment incidents in foster homes were abstracted from Child Protective Services investigation records for the years 1984-1988. Comparisons were made to community reports. Results indicated that foster families had over a three-fold increased frequency of maltreatment reports as compared to nonfoster families. Report frequency was highest for physical abuse with a seven-fold risk of report as compared to nonfoster families. Overall, 20% of foster care reports were substantiated as compared to 35% of nonfoster reports, although the risk of having a substantiated report was significantly higher in foster care. The distribution of report types in foster care differed from those in the community with physical abuse the most frequent allegation in foster care, as compared to neglect as the most frequent allegation in the community. Explanations for these findings including differences in criteria for report and substantiation are advanced.

Non-A, non-B post-transfusion hepatitis. Looking back in the second decade.

OBJECTIVE: To determine the long-term course of non-A, non-B post-transfusion hepatitis. DESIGN: Follow-up in 1989 to 1992 of patients prospectively identified as having contracted non-A, non-B post-transfusion hepatitis between 1972 and 1980. SETTING: A university hospital. PATIENTS: Patients who were prospectively followed from receipt of blood products and in whom otherwise unexplained abnormalities in their serum alanine aminotransferase levels developed without serologic evidence of exposure to hepatitis A or B. MEASUREMENTS: The presence or absence of clinical evidence of liver failure or symptoms of chronic hepatitis. RESULTS: Of 90 patients identified in the 1970s, 80 were recontacted and evaluated between 1989 and 1992. Based on the current status of these 80 patients and on the last known status of the remaining patients, the following observations were made: 1) Although about 40% had some symptoms during the early phase of the disease, none subsequently experienced significant clinical problems related to hepatic inflammation; 2) eight patients (seven with chronic hepatitis) developed hepatic failure; and 3) life-table analysis showed that the probabilities of developing clinical evidence of cirrhosis after 16 years of disease in the entire cohort, in the subgroup who developed chronic hepatitis, in the patients who had hepatitis C, and in those with chronic hepatitis C were 18%, 21%, 17%, and 20%, respectively. CONCLUSIONS: For most of the study patients, non-A, non-B post-transfusion hepatitis was a biochemical and histologic disease that had not yet caused hepatic symptoms. If hepatic failure does occur, it is usually seen only after 10 or more years of disease. Before that time, many infected persons die due to other disease processes.

Detection of silent temporal gaps between narrow-band noise makers having second-formantlike properties of voiceless stop/vowel combinations.

Temporal gap detection thresholds were measured in narrow-band noise-burst markers having acoustic characteristics representative of isolated steady-state second-formant (F2) properties for/p,t,k/paired separately with/i,ae,u,o/. The results revealed that gap detection threshold increased systematically as the difference was increased between the simulated stop and vowel F2 frequencies. A strong positive correlation (r = 0.87) between gap detection threshold and linear marker center frequency difference was highly significant (p < 0.001). Differences in other stimulus features had little influence on gap detection performance. Implications for speech perception are discussed.

Multiple chemical sensitivities syndrome: toward a working case definition.

A study was conducted to identify clinical diagnostic criteria that experts regarded as major for categorizing patients as having multiple chemical sensitivities (MCS) syndrome. A cross-sectional survey of 148 medical practitioners with an interest in, or familiarity with, the condition was performed scoreable questionnaires were returned by 60.1% of those surveyed. The following five criteria, all based on self-reports, were selected as major for diagnosing the syndrome by more than 50% of the respondents: (1) symptoms are reproducible with exposure; (2) condition is chronic; (3) low levels of exposure result in manifestations of the syndrome; (4) symptoms resolve with removal of incitants; and (5) responses occur to multiple, chemically unrelated substances. It is proposed that the major criteria accepted by the majority of survey respondents be used provisionally as the basis for categorizing cases in investigations of MCS syndrome.

Severity of illness and resource use differences among white and black hospitalized elderly.

BACKGROUND: Disparities between races in access to health care services continue to exist. We examined differences in illness severity, charges, and length of stay between white and black hospitalized elderly. METHODS: The study sample was 1184 elderly patients. Data using the Computerized Severity Index were collected for admission, maximum throughout the stay, and discharge. RESULTS: Blacks were admitted significantly more severely ill than whites. At discharge, 96% were severity level 1. At each severity level, blacks had significantly shorter hospitalizations and lower charges. The differences were not explained by disease, surgery, age, sex, hospital, and payer. CONCLUSIONS: Admission severity disparities may exist because of patients' decisions to seek care or provider admitting practices. We need to study whether differences in severity-adjusted resource use are due to underutilization for blacks or overutilization for whites.

Risk factors associated with falls and injuries among elderly institutionalized persons.

A case-control study among 184 matched pairs of patients 65 years of age and older was undertaken to identify risk factors associated with falls and injuries in a long-term care facility in Baltimore, Maryland, in 1984-1985. Patients were matched on length of stay. Variables of interest included sociodemography, functional status, medications, and diagnoses. For all levels of care combined, the following factors were associated (p less than or equal to 0.01) with increased falls: being able to walk (relative odds (RO) = 4.0), age 90 years and older (RO = 3.8), a history of falling (RO = 5.0), and taking a vasodilator (RO = 3.0). Among the 184 fallers, the diagnosis of dementia (RO = 7.5) or taking a diuretic (RO = 7.2) was positively associated with injury (p less than or equal to 0.01). In each of the analyses, medications were associated with falls or injuries, suggesting a feasible intervention. The combination of a history of falling, being able to walk, and being 90 years of age or older increased the relative odds to 51.9 and could alert clinicians to identify and monitor high-risk elderly persons in need of preventive measures.

Gestational age-specific birthweights of twins versus singletons.

In order to more adequately characterize patterns of intrauterine growth retardation in twins, the mean birthweights of all nonanomalous white or black twins born between 24 and 41 weeks of gestation and surviving until discharge over an 11-year period (547 infants) and all similar singletons (19,072 infants) were compared by completed weeks of gestation. Between 24 and 35 weeks of gestation, the mean birthweights for the 547 twins and the 19,072 singletons were comparable and did not consistently differ statistically. From 36 to 41 weeks gestation, however, the difference became large, consistent, and statistically significant for each week at P less than 0.0001. This difference was present among all subgroups of twins, ie, in all males, females, blacks, and whites; it was still evident when the sample was further stratified by both race and sex (black males, white males, black females, white females). These data suggest a pattern of growth retardation in twins compared to singletons which is large, consistent, and statistically significant beginning at 36 weeks gestation. Clinically, these data also suggest the need for ultrasonic examination early in gestation (24-32 weeks) to document normal growth and to provide baseline data, and show the importance of such monitoring later in gestation, specifically after 36 weeks.

Serologic precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate cancer.

We investigated the associations of serum retinol, the carotenoids beta-carotene and lycopene, and tocopherol (vitamin E) with the risk of prostate cancer in a nested case-control study. For the study, serum obtained in 1974 from 25,802 persons in Washington County, MD, was used. Serum levels of the nutrients in 103 men who developed prostate cancer during the subsequent 13 years were compared with levels in 103 control subjects matched for age and race. Although no significant associations were observed with beta-carotene, lycopene, or tocopherol, the data suggested an inverse relationship between serum retinol and risk of prostate cancer. We analyzed data on the distribution of serum retinol by quartiles, using the lowest quartile as the reference value. Odds ratios were 0.67, 0.39, and 0.40 for the second, third, and highest quartiles, respectively.

Association of nonmelanoma skin cancer and actinic keratosis with cumulative solar ultraviolet exposure in Maryland watermen.

To establish the relationship between ultraviolet-B radiation and squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and actinic keratosis (AK), a cross-sectional prevalence survey was performed in a sample of 808 white, male watermen 30 years of age and older residing in the Eastern Shore of Maryland. A measure of personal cumulative ultraviolet-B exposure was determined for each subject from data collected through interviews and field and laboratory measurements. A personal interview elicited skin type, medication history, and other factors. Clinical diagnoses and histologic confirmation were done for current and previously removed skin tumors. The ratio of subjects with SCC to subjects with BCC was approximately 1:1; however, the ratio of BCC to SCC was 1.25:1 because BCC cases were more prone to multiple lesions. Watermen with SCC or AK but not BCC had higher average annual ultraviolet-B doses than age-matched controls. This was particularly marked in watermen younger than 60 years of age. Logistic regression showed that an older age, childhood freckling, and blue eyes significantly increased the risk of the development of all three types of skin tumor. Ease of sunburning was associated with BCC and AK, but not with SCC. Watermen in the upper quartile of cumulative ultraviolet-B exposure had a 2.5 times higher risk for the development of SCC when compared with the lower 3 quartiles. This suggests that high levels of ultraviolet-B exposure are important in SCC occurrence. The risk of AK developing was 1.5 times higher for those whose cumulative ultraviolet-B exposure exceeded the median. The relationship of BCC to cumulative ultraviolet-B exposure was not clear and this suggests that different etiologic mechanisms operate for SCC and BCC.

Evaluation of an infant car seat program in a low-income community.

This study was designed to assess the influence of an infant car seat loan program on car seat utilization in a low-income community. An adjacent community, with no car seat program, was chosen for comparison. Systematic observations were made in the two neighborhoods, and this information was supplemented by telephone interviews. Greater use of infant seats was observed in the intervention community (41%) than in the control community (27%) for infants younger than 6 months old. The rate of observed utilization of infants between 7 and 18 months of age increased to 50% on average, but no significant differences were noted between the two communities. These findings suggest that a community-based loan program can produce short-term increases in car seat use rates for infants, even in a low-income community. A strategy to facilitate continued accessibility to such restraints is needed, however, to maintain these improvements.

Vitamin A, cigarette smoking, and airway obstruction.

The hypothesis that vitamin A, or foods rich in vitamin A such as milk, protects against the development of airway obstruction was tested in a subsample of data from the 1971-1975 National Health and Nutrition Examination Survey. The relative risk (estimated by relative odds) of having airway obstruction, defined as a FEV1/FVC less than or equal to 65%, was measured for different levels of nutrient and food group intakes after adjustment for age, sex, Quetelet Index, caloric intake, and cigarette smoking. Among the white respondents (never smokers or current smokers) whose recalled diet could be considered as typical of their usual diet, the relative odds of having airway obstruction was inversely related to vitamin A intake (x2 for trend = 7.2, p less than 0.01). In the analysis by food groups, the adjusted relative odds of airway obstruction for meat and poultry were 2.4 (95% confidence limits: 1.0 to 5.8) and for milk 1.6 (95% confidence limits: 1.0 to 2.5). The association of airway obstruction with lack of vitamin A or milk intake was clearer among smokers. These findings suggest that a diet poor in vitamin A increases the risk of airway obstruction, and are consistent with the previously reported association of chronic bronchitis, milk intake, and smoking.

Cancer in relatives of leukemic patients with chromosomal rearrangements at rare (heritable) fragile-site locations in their malignant cells.

The cancer occurrence in relatives (N = 407) of 40 case probands (who had leukemia and rearrangements at the same chromosomal location as at least one of 23 recognized rare [heritable] autosomal fragile sites [Sutherland and Mattei 1987]) was compared both to cancer occurrence in relatives (N = 390) of 40 control probands (who had leukemia or other hematologic illness but no recognized chromosomal rearrangements) and to cancer incidence in the general population of the United States. Fragile-site carrier status was not determined in case or control probands. No significant excess of cancer in case relatives, compared with either control relatives or to general (SEER) population expectancies, was found. Furthermore, there was neither evidence of cancer at younger ages, when cases were compared with control relatives, nor an excess of cancer at multiple sites. Male relatives of cases did, however, show a small excess of cancer, especially in older age groups. There was a slight, but not statistically significant, excess of lung cancer in case relatives, with this deviation occurring almost exclusively in relatives of probands having rearrangements at 11q23 and having lymphoid leukemia. It is possible that heritable tendency to chromosomal rearrangement--and thus to cancer--is expressed in such a small proportion of family members that cancer excess in these families could not be detected with the numbers of relatives analyzed in this study, although there was no significant evidence for a hereditary predisposition to cancer in the families of probands with leukemia and with chromosomal rearrangements at the same apparent chromosomal location as rare fragile sites.