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Study of animal-borne infections in the mucosas of patients with inflammatory bowel disease and population-based controls.

Crohn's disease may be triggered by an infection, and it is plausible to consider that such an infection may be animal borne and ingested with our food. There has been considerable interest in the past in determining whether Mycobacterium avium subsp. paratuberculosis (M. avium) might be the etiologic agent in Crohn's disease since it causes a disease in cattle that is similar to Crohn's disease in humans. We aimed to determine if there was an association between Crohn's disease and infection with M. avium or other zoonotic agents and compared the findings with those for patients with ulcerative colitis, unaffected siblings of Crohn's disease patients, or population-based controls without inflammatory bowel disease. Patients under age 50 years with Crohn's disease or ulcerative colitis, unaffected siblings of patients, or healthy controls drawn from a population-based age- and gender-matched registry were enrolled in a study in which subjects submitted to a questionnaire survey and venipuncture. A nested cohort underwent colonoscopy plus biopsy. Samples were batched and submitted to PCR for the detection of M. avium and other zoonotic agents known to cause predominately intestinal disease in cattle, sheep, or swine. Only one patient with ulcerative colitis, no patients with Crohn's disease, and none of the sibling controls were positive for M. avium, whereas 6 of 19 healthy controls were positive for M. avium. Since the control subjects were significantly older than the case patients, we studied another 11 patients with inflammatory bowel disease who were older than age 50 years, and another single subject with ulcerative colitis was positive for M. avium. One other subject older than age 50 years with ulcerative colitis was positive for circovirus, a swine-borne agent of infection. In conclusion, by performing PCR with mucosal samples from patients with Crohn's disease and controls, no association between Crohn's disease and infection with M. avium or any of the other six zoonotic agents studied could be found.

Base Sequence↗

The C677T methylenetetrahydrofolate reductase variant and third trimester obstetrical complications in women with unexplained elevations of maternal serum alpha-fetoprotein.

INTRODUCTION: The C677T MTHFR variant has been associated with the same third trimester pregnancy complications as seen in women who have elevations of maternal serum alpha-fetoprotein (MSAFP). We hypothesized that these women with third trimester pregnancy complications and MSAFP elevations would have an increased frequency of the variant compared to an abnormal study control group (women with MSAFP elevations without pregnancy complications) as well as to normal population controls. METHODS: Women who had unexplained elevations of MSAFP in pregnancy were ascertained retrospectively. The frequency of the C677T MTHFR variant among those women with unexplained elevations of MSAFP who had experienced later pregnancy complications was compared to that of women with unexplained elevations of MSAFP without complications as well as to that of the previously established Manitoba frequency. RESULTS: Women who had complications of pregnancy and an unexplained MSAFP elevation had a higher allele frequency for the C677T MTHFR variant (q = 0.36,) compared to women with MSAFP elevations and normal pregnancy outcomes (q = 0.25, OR 1.73 95% CI 1.25-2.37, p = 0.03). The frequency was also higher than that of the population controls (q= 0.25, OR 1.70 95% CI 1.11-2.60, p = 0.007). The frequency in women with MSAFP elevations without pregnancy complications was not significantly different from that of the population controls (p = 0.41). CONCLUSION: Women with unexplained elevations of MSAFP and who experience complications in later pregnancy are more likely to have one or two alleles of the C677T MTHFR variant.

Cytosine↗

Response to selection for milk yield in Holsteins.

Data were collected for 11 yr in five institutional herds in Virginia to determine the response to selection for milk yield and to examine correlated response in other traits. A randombred control population allowed separation of genetic and environmental effects. The genetic base was the same for both control and selection groups, and little directional selection took place in the control population. The control line was generated from 12 sire lines initiated by 8 unproven sires sampled by artificial insemination and sons of 4 proven bulls. Four bulls high for Predicted Difference milk were used in the selection group each year. By three methods of analysis, best linear unbiased prediction, deviation of selection from control group means, and least squares differences between selection and control for milk, fat, and fat percentage were: 370, 374, 438 kg; 10, 8, 6 kg; and -.02, -.02, and -.10%. These agree closely with expectations from modified contemporary comparisons of the bulls. Differences in fat percentages were more variable although all analyses indicated a negative correlated response to selection for milk yield. Generation effects varied with method of analysis but were generally small and agreed with differences in sire Predicted Differences. Response differed across herds.

Animals↗

A role for the Clostridium perfringens beta2 toxin in bovine enterotoxaemia?

Non-enterotoxigenic type A Clostridium perfringens are associated with bovine enterotoxaemia, but the alpha toxin is not regarded as responsible for the production of typical lesions of necrotic and haemorrhagic enteritis. The purpose of this study was to investigate the putative role of the more recently described beta2 toxin. Seven hundred and fourteen non-enterotoxigenic type A C. perfringens isolated from 133 calves with lesions of enterotoxaemia and high clostridial cell counts (study population) and 386 isolated from a control population of 87 calves were tested by a colony hybridisation assay for the beta2 toxin. Two hundred and eighteen (31%) C. perfringens isolated from 83 calves (62%) of the study population and 113 (29%) C. perfringens isolated from 51 calves (59%) of the control population tested positive with the beta2 probe. Pure and mixed cultures of four C. perfringens (one alpha+beta2+, one alpha+enterotoxin+ and two alpha+) were tested in the ligated loop assay in one calf. Macroscopic haemorrhages of the intestinal wall, necrosis and haemorrhages of the intestinal content, and microscopic lesions of necrosis and polymorphonuclear and mononuclear cell infiltration of the intestinal villi were more pronounced in loops inoculated with the alpha and beta2-toxigenic C. perfringens isolate. These results suggest in vivo synergistic role of the alpha and beta2 toxins in the production of necrotic and haemorrhagic lesions of the small intestine in cases of bovine enterotoxaemia. However, isolation of beta2-toxigenic C. perfringens does not confirm the clinical diagnosis of bovine enterotoxaemia and a clostridial cell counts must still be performed.

Animals↗

Thyroid function in a population of children with attention deficit hyperactivity disorder.

OBJECTIVE: To determine the prevalence of thyroid hormone abnormalities and generalized resistance to thyroid hormone in a population of children with attention deficit hyperactivity disorder (ADHD) as compared to reference ranges determined from a control population and hence to determine if routine thyroid hormone screening in children with non-familial ADHD is indicated. METHOD: Children attending the State Child Development Centre in Perth, Western Australia with ADHD, as defined by the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) provided the study population. The control population consisted of 353 normal children with a history of allergy in whom radioallergosorbent (RAST) testing was being performed. RESULTS: The prevalence of thyroid hormone abnormalities in the study population was 2.3% (95% CI 0.6%, 5.7%). There were no cases of generalized resistance to thyroid hormone. The prevalence of thyroid hormone abnormalities in the general population of children and adolescents has been reported to vary between 1 and 3.7%. CONCLUSION: Routine thyroid hormone screening is not indicated in children with non-familial ADHD.

Adolescent↗

Lipoprotein lipase gene mutations D9N and N291S in four pedigrees with familial combined hyperlipidaemia.

The role of the lipoprotein lipase (LPL) gene in familial combined hyperlipidaemia (FCH) is unclear at present. We screened a group of 28 probands with familial combined hyperlipidaemia and a group of 91 population controls for two LPL gene mutations, D9N and N291S. LPL-D9N was found in two probands and one normolipidaemic population control. LPL-N291S was found in four probands and four population controls. Subsequently, two pedigrees from probands with the D9N mutation and two pedigrees from probands with the N291S mutation were studied, representing a total of 24 subjects. Both LPL gene mutations were associated with a significant effect on plasma lipids and apolipoproteins. Presence of the D9N mutation (n = 7) was associated with hypertriglyceridaemia [2.69 +/- 1.43 (SD) mmol L-1] and reduced plasma high-density lipoprotein cholesterol (HDL-C) concentrations (0.92 +/- 0.21 mmol L-1) compared with 11 non-carriers (triglyceride 1.75 +/- 0.64 mmol L-1; HDL-C 1.23 +/- 0.30 mmol L-1, P = 0.03 and P = 0.025 respectively). LPL-D9N carriers had higher diastolic blood pressures than non-carriers. LPL-N291S carriers (n = 6) showed significantly higher (26%) apo B plasma concentrations (174 +/- 26 mg dL-1) than non-carriers (138 +/- 26 mg dL-1; P = 0.023), with normal post-heparin plasma LPL activities. Linkage analysis revealed no significant relationship between the D9N or N291S LPL gene mutations and the FCH phenotype (hypertriglyceridaemia, hypercholesterolaemia or increased apo B concentrations). It is concluded that the LPL gene did not represent the major single gene causing familial combined hyperlipidaemia in the four pedigrees studied, but that the LPL-D9N and LPL-N291S mutations had significant additional effects on lipid and apolipoprotein phenotype.

Adult↗

Rickets associated with long-term anticonvulsant therapy in a pediatric outpatient population.

Over a 12-month period, an ambulatory pediatric population receiving long-term anticonvulsants was surveyed for the presence of biochemical and radiologic rickets. There were 74 treated children and 95 matched controls. Elevations of serum alkaline phosphatase activity occurred in 31 of the 74 (42%) treated children (23 of 47 children between 2 and 10 years and 8 of 21 children between 10 and 16 years). This frequency of abnormal values was significantly greater than that which occurred in our control population. Calcium and phosphorus abnormalities were minimal in both treated and control populations. Radiologic rickets occurred in 6 of the 74 (8%) of the treated children and in none of the control population. Neither the severity of the rickets nor the degree of hyperalkaline phosphatasemia were correlated with age of the patient, duration, and/or dose of anticonvulsant therapy.

Adolescent↗

Occurrence of mesangial IgA and IgM deposits in a control necropsy population.

Kidney sections were obtained from 200 consecutive control necropsies of patients who died of traumatic injuries, with no clinical history of renal disease or other organic disease discovered at necropsy. Mesangial IgA as the predominant immunoglobulin was found in 8/200 (4%) cases, with accompanying IgM in two of them; and IgM alone in two (1%) subjects. Deposits of C3 alone in blood vessels was observed in nine (4.5%) cases. The glomerular morphology was essentially normal or minor change only, with one case showing diffuse mesangial hypercellularity. The high incidence of mesangial IgA deposits in the local apparently healthy population may reflect some common feature of the antigen(s) or complex involved. They may be of environmental, dietary or infectious origin. It is possible that many of these "spontaneous" deposits in the glomerular mesangium may result from the clearance of circulating non-nephritogenic immune complexes.

Adolescent↗

Rare SP-A alleles and the SP-A1-6A(4) allele associate with risk for lung carcinoma.

Next to cigarette smoking, genetic factors may contribute to lung cancer risk. Pulmonary surfactant components may mediate response to inhaled carcinogenic substances and/or play a role in lung function and inflammation. We studied associations between surfactant protein (SP) genetic variants and risk in lung cancer subgroups. Samples (n=308) were genotyped for SP-A1, -A2, -B, and -D marker alleles. These included 99 patients with small cell lung carcinoma (SCLC, n=31), or non-SCLC (NSCLC, n=68) consisting of squamous cell carcinoma (SCC, n=35), and adenocarcinoma (AC) (n=23); controls (n=99) matched by age, sex, and smoking status (clinical control) to SCLC and NSCLC; and 110 healthy individuals (population control). We found (a) no significant marker associations with SCLC, (b) rare SP-A2 (1A9) and SP-A1 (6A11) alleles associate with NSCLC risk when compared with population control, (c) the same alleles (1A9, 6A11) associate with risk for AC when compared with population (6A11) or clinical control (1A9), and (d) the SP-A1-6A4 allele (found in approximately 10% of the population) associates with SCC, when compared with population or clinical control. A correlation between SP-A variants and lung cancer susceptibility appears to exist, indicating that SP-A alleles may be useful markers of lung cancer risk.

Adult↗

Role of alcohol in recurrences of atrial fibrillation in persons less than 65 years of age.

The role of alcohol in recurrences of atrial fibrillation (AF) was assessed in a consecutive series of 98 patients (75 men) aged less than 65 years. In addition to etiologic assessment using clinical and laboratory methods and echocardiography, the patients' drinking habits were evaluated by recording the amount of alcohol used during the week preceding AF, by responses to the CAGE (Cut, Annoying, Guilt, Eye; see below) questionnaire (a screening test for alcohol abuse) and by selected laboratory tests. Two groups of control subjects were studied: 98 sex- and age-matched patients admitted to the emergency ward for acute illnesses, and 50 subjects selected randomly from the local out-of-hospital population. The mean alcohol consumption among men during the study week was 186 g (median 45 g; range 0 to 2,100 g) among patients, whereas among male hospital and population control subjects it was 86 g (30 g; 0 to 1,050 g) and 94 g (35 g; 0 to 630 g), respectively. When the weekly alcohol consumption was analyzed in 3 categories (0; 1 to 210 g; greater than 210 g), there was a significant difference between AF cases and hospital control patients (p = 0.03), but not between AF cases and population control subjects. Multivariate analysis of data of AF cases and population control subjects showed that alcohol intake and a positive response to 1 or more of the CAGE questions were independently related to AF in men. Other independent risk factors were the presence of heart disease, low serum potassium and lack of sleep or experience of excess psychologic stress, or both.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A toxicological examination of whitefish (Coregonus clupeaformis) and northern pike (Esox lucius) exposed to uranium mine tailings.

Operation of the Gunnar uranium mine, in nothern Saskatchewan, Canada, from 1955 to 1964, resulted in the deposition of radioactive tailings in Langley Bay, a small bay connected to Lake Athabasca. Previous publications have described the contamination of the sediments, water, macrophytes and fish of this area. The present study compares the parasite infestations, blood hematocrit, histopathology and condition factor (K) of the Langley Bay whitefish and northern pike populations with these factors measured for control populations from Lake Athabasca. No significant differences could be found, in any of the physiological parameters measured, between the contaminated and control populations.

Animals↗

Risk factors for ectopic pregnancy: a comprehensive analysis based on a large case-control, population-based study in France.

This case-control study was associated with a regional register of ectopic pregnancy between 1993 and 2000 in France. It included 803 cases of ectopic pregnancy and 1,683 deliveries and was powerful enough to investigate all ectopic pregnancy risk factors. The main risk factors were infectious history (adjusted attributable risk = 0.33; adjusted odds ratio for previous pelvic infectious disease = 3.4, 95% percent confidence interval (CI): 2.4, 5.0) and smoking (adjusted attributable risk = 0.35; adjusted odds ratio = 3.9, 95% CI: 2.6, 5.9 for >20 cigarettes/day vs. women who had never smoked). The other risk factors were age (associated per se with a risk of ectopic pregnancy), prior spontaneous abortions, history of infertility, and previous use of an intrauterine device. Prior medical induced abortion was associated with a risk of ectopic pregnancy (adjusted odds ratio = 2.8, 95% CI: 1.1, 7.2); no such association was observed for surgical abortion (adjusted odds ratio = 1.1, 95% CI: 0.8, 1.6). The total attributable risk of all the factors investigated was 0.76. As close associations were found between ectopic pregnancy and infertility and between ectopic pregnancy and spontaneous abortion, further research into ectopic pregnancy should focus on risk factors common to these conditions. In terms of public health, increasing awareness of the effects of smoking may be useful for ectopic pregnancy prevention.

Adult↗

A prevalence study of folate deficiency in a psychiatric in-patient population.

Controlled clinical trials in the UK have shown folate deficiency in psychiatric patients, and it has been suggested that such deficiency is most likely to occur among patients with affective disorders. Studies have led to the use of folate as an adjunct to therapy in such patients. The present paper describes a preliminary investigation into the red cell folate status of psychiatric patients in a general hospital unit compared with age- and sex-matched healthy controls, using up-to-date assays and strict entry criteria and overall improved methods on previous studies. The study showed that, although there is a trend for psychiatric patients to have lower serum folate levels than controls, there is no statistically significant difference in folate levels as measured by red cell folate, a more reliable measure of folate status, between healthy controls and psychiatric patients, and all but one of the patients had normal haematological indices.

Adult↗

Anthropometric characteristics of X-linked hypophosphatemia.

An anthropometric study was undertaken to assess head proportions of patients with X-linked hypophosphatemia (XLH). Fourteen morphometric parameters of the head were measured and 10 cephalic indices calculated in 82 affected persons (57 females and 25 males) from 55 unrelated families with XLH, and compared with the results obtained in the group of their healthy relatives (37 females and 33 males), as well as with general population control values. Normalized values (SD, z-score) were analyzed statistically. The group of healthy relatives, both males and females, differed significantly from Polish population control values in most of the normalized variables measured, making population control values useless as a control group for the analyzed XLH group. Intrafamilial values of cephalic parameters in healthy relatives of the XLH patients were finally applied for statistical analysis. Generally patients with XLH showed highly statistically significant increase in head length (males 0.95 +/- 1.07 vs. -0.37 +/- 1.02, females 0.57 +/- 1.59 vs. -0.06 +/- 1.15), significant decrease in occipital breadth (males -0.56 +/- 1.27 vs. 0.70 +/- 1.28, females -0.59 +/- 1.7 vs. 0.13 +/- 1.1) and several milder anomalies of craniofacial proportions. Mean cephalic index was significantly lower in XLH patients when compared with the healthy relatives (males -0.909 vs. 0.278 P < 0.0001, females -0.705 vs. 0.381 P = 0.007). The cephalic changes were found both in XLH children and XLH adults and were more pronounced in affected males than in females. There were no differences between offspring born by hypophosphatemic and normophosphatemic mothers.

Adolescent↗

A comparison of umbilical cord blood gas values between newborns with and without true knots.

OBJECTIVE: To compare umbilical cord blood gas values in newborns with and without true knots, and to assess the potential impact of true knot formation on cord blood gases. METHODS: Twelve newborn infants with true umbilical cord knots were identified and compared with a random control population of 104 newborn infants without true knots. The two groups were analyzed for 11 maternal-fetal variables to determine if they were comparable. Subsequently, the principal outcome variable of the study was evaluated: a comparison between the umbilical arterial and venous blood gas results of the true knot and control populations. RESULTS: The true knot and control populations were comparable with respect to the maternal-fetal variables analyzed. The umbilical cord blood gas values did not differ between groups, except for a slightly lower umbilical artery bicarbonate value in the control group (22.0 mEq/L) versus the true knot group (24.5 mEq/L), P = .025. There was no significant difference in the incidence of acidemia (umbilical artery pH less than 7.20) between the two groups. CONCLUSION: The presence of true umbilical cord knots does not alter the incidence of umbilical artery acidemia or change umbilical cord blood gas values. Review of the pertinent obstetric literature supports the hypothesis that true umbilical cord knots lack clinical significance.

Adolescent↗

Life expectancy of patients with chronic nonleukemic myeloproliferative disorders.

This study determines, within the frame of current therapeutic possibilities, the impact of chronic nonleukemic myeloproliferative disorders on expected survival. The survival data for 1067 patients (454 with polycythemia vera, 247 with essential thrombocythemia, and 366 with idiopathic myelofibrosis) were collected from 38 Spanish institutions. The actuarial survival probability of each group of patients was compared with that of the age-matched and sex-matched control population. The survival of the patients with polycythemia vera and essential thrombocythemia did not differ from that of the control population (P = 0.92 and, 0.22, respectively), whereas the survival of the patients with idiopathic myelofibrosis was strikingly reduced with respect to the control population (P = 0.0000000007). Thus, in terms of survival, current therapeutic procedures may be considered as quite satisfactory in patients with polycythemia vera and essential thrombocythemia. On the other hand, due to poor survival of patients with idiopathic myelofibrosis, new therapeutic approaches for this condition are clearly needed.

Aged↗

Vertebral deformities in rheumatoid arthritis: a comparison with population-based controls.

BACKGROUND: Previous studies have shown an increased prevalence of osteoporosis in rheumatoid arthritis (RA), but the extent of osteoporotic fractures is not clarified. The aim of this study was to compare the prevalence of vertebral deformities in a representative, population-based cohort of female patients with RA with that in matched controls, and to examine the relationship between deformities and RA, bone mineral density (BMD), and corticosteroid use. METHODS: Female patients (mean age, 63.0 years; range, 50.7-73.6 years) were recruited from a county register of patients with RA. Population controls were matched for age, sex, and residential area. Participants had thoracolumbar radiographs taken according to a standardized procedure, and BMD was measured at the hip and spine (L2-L4). RESULTS: The overall number of vertebral deformities was substantially higher in the RA group compared with controls (147 vs 51, applying the morphometric criteria), with a highly significant difference between patients and controls regarding the presence of multiple deformities measured morphometrically (11.2% vs 4.8%; odds ratio, 2.60; 95% confidence interval, 1.21-6.04) and moderate or severe deformities measured semiquantitatively (17.3% vs 10.0%; odds ratio, 2.00; 95% confidence interval, 1.11-3.74). In Poisson regression analysis, vertebral deformities were independently associated with RA, BMD, and long-term corticosteroid use. CONCLUSIONS: Vertebral deformities are markedly increased in patients with RA compared with controls, especially regarding severe and multiple deformities. A diagnosis of RA was associated with vertebral deformities independently of BMD and long-term corticosteroid use. These findings have important implications for prevention of established osteoporosis in RA.

Aged↗

Analysis of DNA strand break induction and repair in plants from the vicinity of Chernobyl.

For 3 years following the Chernobyl accident, DNA repair efficiency was studied in irradiated and control populations of various plant species. Compared with the control populations, some irradiated populations exhibited increases in the yield of DNA single-strand breaks per unit dose of challenge radiation. The effect was registered in low-dose-rate alpha-irradiated populations, but was absent in plant populations growing in conditions of low-dose-rate beta-irradiation. The efficiency of single-strand DNA repair was identical in control and irradiated populations and approximated 100%.

Accidents↗