The feasibility of existing JADAS10 cut-off values in clinical practice: a study of data from The Finnish Rheumatology Quality Register.

BACKGROUND: The ten-joint juvenile arthritis disease activity score (JADAS10) is designed to measure the level of disease activity in non-systemic juvenile idiopathic arthritis by providing a single numeric score. The clinical JADAS10 (cJADAS10) is a modification of the JADAS10 that excludes erythrocyte sedimentation rate (ESR). Three different sets of JADAS10/cJADAS10 cut-offs for disease activity states have been published, i.e., the Backström, Consolaro, and Trincianti cut-offs. The objective of this study was to investigate the performance of existing JADAS10 cut-offs in real-life settings using patient data from The Finnish Rheumatology Quality Register (FinRheuma). METHODS: Data were collected from the FinRheuma register. The proportion of patients with an active joint count (AJC) above zero when classified as being in clinically inactive disease (CID) or low disease activity (LDA) groups according to existing JADAS10/cJADAS10 cut-off levels were analyzed. RESULTS: A significantly larger proportion of the patients classified as being in CID had an AJC > 0 when using the JADAS10/cJADAS10 cut-offs by Trincianti et al. compared to those for the other cut-offs. In the LDA group, a significantly larger proportion of the polyarticular patients (35%/29%) had an AJC of two when Trincianti JADAS10/cJADAS10 cut-offs were used compared with when Backström (11%/10%) and Consolaro (7%/3%) JADAS10/cJADAS10 cut-offs were used. CONCLUSIONS: We found the cut-offs proposed by Consolaro et al. to be the most feasible, since these cut-off levels for CID do not result in the misclassification of active disease as remission, and the proportion of patients with AJC > 1 in the LDA group is lowest using these cut-offs.

Juvenile idiopathic arthritis patients with low inflammatory activity have increased adiposity.

OBJECTIVES: The aim of this study was to assess the effect of juvenile idiopathic arthritis (JIA), its subtypes and disease activity on anthropometric measurements, body composition, and nutritional parameters. METHOD: A cross-sectional cohort of 40 JIA patients, aged 3-10 years, was compared with 40 healthy children matched for age and gender. Concentrations of nutritional and inflammatory biomarkers in the blood, anthropometric measures, and clinical status were recorded and the parents filled in a 7-day food diary and completed the Childhood Health Assessment Questionnaire (CHAQ). RESULTS: The JIA patients had low disease activity: 60% had inactive disease, the median CHAQ score was 0.125, and the median erythrocyte sedimentation rate (ESR) was 6 mm/h. Significantly higher values for central and peripheral adiposity were found in JIA patients compared with in healthy controls [waist circumference mean (SD) 55.9 (4.9) vs. 53.4 (3.7) cm, p < 0.0001, and biceps skinfold thickness 6.2 (2.3) vs. 5.3 (1.7) cm, p = 0.035, respectively], and obesity/overweight was more common (30% vs. 12.5%, p = 0.056, respectively) despite no differences in weight-for-height. The intake of energy (kcal/day) was significantly higher in the JIA patients (p = 0.036). The nutritional biomarkers were comparable in both groups. The JIA subtype and disease activity did not affect body composition, energy intake, or the nutritional biomarkers. CONCLUSIONS: Even JIA patients with low disease activity have a higher central and peripheral adiposity and a higher energy intake than their healthy peers. Neither disease subtype nor disease activity had any association with changes in body composition.

Birth weight is the most important predictor of abnormal retinal vascularisation in moderately preterm infants.

AIM: To find predictors of abnormal retinal vascularisation in moderately to late preterm newborn infants considered to have no risk of developing retinopathy of prematurity. METHODS: Seventy-eight infants (34 girls) were recruited from a longitudinal study of otherwise healthy premature children born at a gestational age of 32 + 0-36 + 6 weeks. Retinal vessel morphology was evaluated at mean postnatal age 7 days. Insulin-like growth factor-I (IGF-I) levels were analysed in umbilical cord blood. RESULTS: Of the 78 infants, 21 (27%) had abnormal retinal vessel morphology; they had significantly lower median (range) birth weight [1850 g, (1190-3260), vs. 2320, (1330-3580), p < 0.0001], shorter birth length [43.0 cm, (38-49), vs. 46.0, (40-50), p < 0.0001] and smaller head circumference [31.0 cm, (27.7-34.0), vs. 32.0, (27.5-36.5), p = 0.003]. They also had significantly lower gestational age [34 + 1 weeks, (32 + 2-35 + 3), vs. 34 + 6, (32 + 2-36 + 6), p = 0.004] and mean ± SD IGF-I levels (24.6 ± 17.0 µg/L vs. 46.7 ± 21.5, p < 0.0001). A higher percentage of these infants were small for gestational age (57.1% vs. 15.8%, p = 0.001), and maternal hypertension/preeclampsia rates were also higher (47.6% vs. 19.3%, p = 0.03). Step-wise logistic regression showed that birth weight was the strongest predictor of abnormal retinal vascularisation (p < 0.0001, odds ratio 0.040, 95% confidence interval 0.007-0.216). CONCLUSION: In this population of moderately to late preterm newborns, birth weight appeared to affect the retinal vascular system.

Ophthalmological findings in children and adolescents with Silver-Russell syndrome.

AIM: To evaluate ophthalmological findings in children with Silver-Russell syndrome (SRS). METHODS: An ophthalmological evaluation including visual acuity (VA), refraction, strabismus, near point of convergence (NPC), slit-lamp examination, ophthalmoscopy, axial length measurements and full-field electroretinogram was performed on 18 children with SRS (8 girls, 10 boys; mean age 11.6 years). Fundus photographs were taken for digital image analysis. Data were compared with data on an age- and gender-matched reference group (ref) of school children (n=99). RESULTS: Seventeen out of 18 children with SRS had ophthalmological abnormalities. Best corrected VA of the best eye was <0.1 log of the minimal angle of resolution in 11 children (ref n=98) (p<0.0001), and 11 children had refractive errors (ref n=33) (p=0.05). Anisometropia (≥1 dioptre) was noted in three of the children (ref n=3) (p=0.046). Subnormal stereo acuity and NPC were found in 2/16 (ref=0) (p=0.02). The total axial length in both eyes was shorter compared with that in controls (p<0.006 and p<0.001). Small optic discs were found in 3/16, large cup in 3/16 and increased tortuosity of retinal vessels in 4/13 children with SRS. CONCLUSION: Children with SRS, who are severely intrauterine growth retarded, show significant ophthalmological abnormalities. Based on the present findings, ophthalmological examination is recommended in children with SRS.

Ophthalmological findings in children and young adults with genetically verified mitochondrial disease.

AIM: To describe ophthalmological phenotypes in patients with mitochondrial disease and known genotypes. METHODS: A retrospective study was performed on 59 patients (29 male, 30 female) with a mean age of 11.8 years who had mitochondrial disease with known DNA mutations. Fifty-seven of the 59 subjects underwent a detailed ophthalmological examination including visual acuity (VA), eye motility, refraction, slit-lamp examination, ophthalmoscopy and, in almost one-half of the cases, a full-field electroretinogram (ERG). RESULTS: Forty-six (81%) of the patients had one or more ophthalmological findings such as ptosis (n = 16), reduced eye motility (n = 22) including severe external ophthalmoplegia (n = 9), strabismus (n = 4), nystagmus (n = 9), low VA (n = 21), refractive errors (n = 26), photophobia (n = 4), and partial or total optic atrophy (n = 25). Pigmentation in the macula and/or periphery was noted in 16 patients. In 10/27 investigated individuals with full field ERG, retinal dystrophy was recorded in six different genotypes representing Kearns-Sayre syndrome (n = 5), Leigh syndrome (n = 1), Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) (n = 1), Myoclonus epilepsy with red ragged fibres (MERRF) (n = 1), Leber hereditary optic neuropathy (n = 1) and mitochondrial myopathy (n = 1). CONCLUSION: The results show that a majority of patients with mitochondrial disorders have ophthalmological abnormalities. We recommend that an ophthalmological examination, including ERG, be performed on all children and adolescents who are suspected of having a mitochondrial disease.

Virus-induced gene silencing (VIGS) as a reverse genetic tool to study development of symbiotic root nodules.

Virus-induced gene silencing (VIGS) can provide a shortcut to plants with altered expression of specific genes. Here, we report that VIGS of the Nodule inception gene (Nin) can alter the nodulation phenotype and Nin gene expression in Pisum sativum. PsNin was chosen as target because of the distinct non-nodulating phenotype of nin mutants in P. sativum, Lotus japonicus, and Medicago truncatula. The vector based on Pea early browning virus (PEBV) was engineered to carry one of three nonoverlapping fragments (PsNinA, PsNinB, and PsNinC) derived from the PsNin cDNA. Vector inoculation was mediated by agroinfiltration and, 2 weeks later, a Rhizobium leguminosarum bv. viceae culture was added in order to induce root nodulation. At this time point, it was estimated that systemic silencing was established because leaves of reference plants inoculated with PEBV carrying a fragment of Phytoene desaturase displayed photo bleaching. Three weeks after Rhizobium spp. application, plants inoculated with a control vector nodulated normally, whereas nodulation was almost eliminated in plants inoculated with a vector carrying PsNinA and PsNinC. For plants inoculated with a vector carrying PsNinB, nodulation was reduced by at least 45%. Down-regulation of PsNin transcripts in plants inoculated with vectors carrying PsNin cDNA fragments was confirmed and these plants displayed a relative increase in the root/shoot ratio, as expected if nitrogen fixation had been impaired.

Maternal breast-milk and intestinal bifidobacteria guide the compositional development of the Bifidobacterium microbiota in infants at risk of allergic disease.

BACKGROUND: The sources and the impact of maternal bacteria on the initial inoculum of the intestinal microflora of newborn infants remain elusive. OBJECTIVE: To assess the association between maternal breast-milk and fecal bifidobacteria and infants' fecal bifidobacteria. METHODS: Sixty-one mother-infant pairs were included, special emphasis being placed on the maternal allergic status. Bifidobacteria were analysed by a direct PCR method in fecal samples from mothers at 30-35 weeks of gestation and from infants at 1 month of age and from breast-milk samples 1 month post-partum. RESULTS: Fecal Bifidobacterium adolescentis and Bifidobacterium bifidum colonization frequencies and counts among mother-infant pairs correlated significantly (P=0.005 and 0.02 for frequencies, respectively, and P=0.002 and 0.01 for counts, respectively). Only infants of allergic, atopic mothers were colonized with B. adolescentis. Each of the breast-milk samples contained bifidobacteria [median 1.4 x 10(3) bacterial cells/mL; interquartile range (IQR) 48.7-3.8 x 10(3)]. Bifidobacterium longum was the most frequently detected species in breast-milk. Allergic mothers had significantly lower amounts of bifidobacteria in breast-milk compared with non-allergic mothers [median 1.3 x 10(3) bacterial cells/mL (IQR 22.4-3.0 x 10(3)) vs. 5.6 x 10(3) bacterial cells/mL (1.8 x 10(3)-1.8 x 10(4)), respectively, (P=0.004)], and their infants had concurrently lower counts of bifidobacteria in feces [3.9 x 10(8) bacterial cells/g (IQR 6.5 x 10(6)-1.5 x 10(9)) in infants of allergic mothers, vs. 2.5 x 10(9) bacterial cells/g (6.5 x 10(8)-3.2 x 10(10)) in infants of non-allergic mothers, P=0.013]. CONCLUSIONS: Breast-milk contains significant numbers of bifidobacteria and the maternal allergic status further deranges the counts of bifidobacteria in breast-milk. Maternal fecal and breast-milk bifidobacterial counts impacted on the infants' fecal Bifidobacterium levels. Breast-milk bacteria should thus be considered an important source of bacteria in the establishment of infantile intestinal microbiota.

Visual function and ocular features in children and adolescents with attention deficit hyperactivity disorder, with and without treatment with stimulants.

AIMS: To investigate visual function and ocular features in children with attention deficit hyperactivity disorder (AD/HD) and establish whether treatment with stimulants is reflected in functioning of the visual system. METHODS: Detailed ophthalmologic evaluations without and with stimulants were performed in 42 children (37 boys) with AD/HD, mean age 12 years, and compared with a reference group (ref; n=50; mean age 11.9 years; 44 boys). For a comparison between two groups, Mann-Whitney's U-test was used for ordered and continuous variables; for dichotomous variables, Fisher's exact test was used. For paired comparison (with and without treatment), sign test was used. RESULTS: In all, 83% had visual acuity of >0.8 (<0.1 logMAR) without treatment, 90% with stimulants (ref 98%; P=0.032 and n.s., respectively). Heterophoria was found in 29% without, and in 27% with, stimulants (ref 10%; P=0.038 and n.s., respectively) and subnormal stereovision (>60 s of arc) in 26% (ref 6%; P=0.016) without stimulants, and in 27%, with (P=0.014). Abnormal convergence (>6 cm or absent) was noted in 24% (ref 6%; P=0.031) without treatment and in 17%, with (n.s.). Astigmatism (> or =1.0 D) was observed in 24% (ref 6%; P=0.03), and signs of visuoperceptual problems in 21% (ref 2%; P=0.007). We found smaller optic discs (n=8/38) and neuroretinal rim areas (n=7/38) (P<0.0001) and decreased tortuosity of retinal arteries (n=6/34) (P=0.0002) than that of controls. CONCLUSIONS: Children with AD/HD had a high frequency of ophthalmologic findings, which were not significantly improved with stimulants. They presented subtle morphological changes of the optic nerve and retinal vasculature, indicating an early disturbance of the development of these structures.

Mitochondrial myopathy with exercise intolerance and retinal dystrophy in a sporadic patient with a G583A mutation in the mt tRNA(phe) gene.

We describe a second patient with the 583G>A mutation in the tRNA(phe) gene of mitochondrial DNA (mtDNA). This 17-year-old girl had a mitochondrial myopathy with exercise intolerance and an asymptomatic retinopathy. Muscle investigations showed occasional ragged red fibers, 30% cytochrome c oxidase (COX)-negative fibers, and reduced activities of complex I+IV in the respiratory chain. The mutation was heteroplasmic (79%) in muscle but undetectable in other tissues. Analysis of single muscle fibers revealed a significantly higher level of mutated mtDNA in COX-negative fibers. Our study indicates that the 583G>A mutation is pathogenic and expands the clinical spectrum of this mutation.

Visual and ocular findings in children adopted from eastern Europe.

AIMS: To evaluate ophthalmological findings in children adopted from eastern Europe. METHODS: A prospective study on 72/99 children, born 1990-5 and adopted from eastern Europe to western Sweden during 1993-7 was performed. The children (41 boys; mean age 7.5 years) were compared with an age and sex matched reference group ("ref") of Swedish children. RESULTS: 78% of the adopted children had abnormal ocular findings. 26% (ref 4%) had visual acuity (VA) of the better eye < or = 0.5 (> or = 0.3 logMAR) (p = 0.0001) and 8% (ref 0%) were visually impaired (p = 0.01). Amblyopia was found in 15% (ref 2%) (p = 0.005). 22% (ref 10%) were hyperopic (> or = 2.0 D SE) (NS) and 10% (ref 1%) were myopic (> or = 0.5 D SE) (p = 0.03). Astigmatism (> or = 0.75 D) was found in 51% (ref 23%) (p = 0.004). 32% (ref 2%) had strabismus (p<0.0001), mostly esotropia. Four cases had bilateral optic nerve hypoplasia, in three of whom a history of suspected prenatal alcohol exposure was documented. One child had congenital glaucoma. Signs of visuoperceptual problems were recorded in 37% (ref 1%) (p<0.0001). CONCLUSION: In this study, children adopted from eastern Europe had a high frequency of ophthalmological findings. Consequently, it is strongly recommended that an ophthalmological examination be performed in these children after arrival in their new home country.

Cell biological changes of outer cortical root cells in early determinate nodulation.

In the symbiosis of leguminous plants and Rhizobium bacteria, nodule primordia develop in the root cortex. This can be either in the inner cortex (indeterminate-type of nodulation) or outer cortex (determinate-type of nodulation), depending upon the host plant. We studied and compared early nodulation stages in common bean (Phaseolus vulgaris) and Lotus japonicus, both known as determinate-type nodulation plants. Special attention was paid to the occurrence of cytoplasmic bridges, the influence of rhizobial Nod factors (lipochitin oligosaccharides [LCOs]) on this phenomenon, and sensitivity of the nodulation process to ethylene. Our results show that i) both plant species form initially broad, matrix-rich infection threads; ii) cytoplasmic bridges occur in L. japonicus but not in bean; iii) formation of these bridges is induced by rhizobial LCOs; iv) formation of primordia starts in L. japonicus in the middle root cortex and in bean in the outer root cortex; and v) in the presence of the ethylene-biosynthesis inhibitor aminoethoxyvinylglycine (AVG), nodulation of L. japonicus is stimulated when the roots are grown in the light, which is consistent with the role of cytoplasmic bridges during nodulation of L. japonicus.

Importance of intestinal colonisation in the maturation of humoral immunity in early infancy: a prospective follow up study of healthy infants aged 0-6 months.

AIM: To evaluate the role of intestinal microflora and early formula feeding in the maturation of humoral immunity in healthy newborn infants. STUDY DESIGN: Sixty four healthy infants were studied. Faecal colonisation with Bacteroides fragilis group, Bifidobacterium-like, and Lactobacillus-like bacteria was examined at 1, 2, and 6 months of age, and also the number of IgA-secreting, IgM-secreting, and IgG-secreting cells (detected by ELISPOT) at 0, 2, and 6 months of age. RESULTS: Intestinal colonisation with bacteria from the B fragilis group was more closely associated with maturation of IgA-secreting and IgM-secreting cells than colonisation with the other bacterial genera studied or diet. Infants colonised with B fragilis at 1 month of age had more IgA-secreting and IgM-secreting cells/10(6) mononuclear cells at 2 months of age (geometric mean (95% confidence interval) 1393 (962 to 2018) and 754 (427 to 1332) respectively) than infants not colonised (1015 (826 to 1247) and 394 (304 to 511) respectively); p = 0.04 and p = 0.009 respectively. CONCLUSIONS: The type of bacteria colonising the intestine of newborns and the timing may determine the immunomodulation of the naive immune system.

Analysis of rat liver foci growth with a quantitative two-cell model after treatment with 2,4,5,3',4'-pentachlorobiphenyl.

A biologically based, quantitative foci-growth model was used to analyze the effect of 20 and 52 weeks treatment with 2,4,5,3', 4'-pentachlorobiphenyl (PCB118) on the development of enzyme-altered foci in rat liver initiated with partial hepatectomy and diethylnitrosamine. Hepatocyte proliferation was examined and the data were used in the selection of division rates for the computer simulations of foci growth. The bromodeoxyuridine-labeling index in foci was generally larger than in nonfocal tissue. A strong correlation was found between foci occurrence and proliferation in focal as well as nonfocal tissue, suggesting that cytotoxicity and regenerative proliferation are involved in the foci growth caused by PCB118. The foci growth model adequately simulated the foci data when certain assumptions were introduced. Given the general view that PCB118 is a nonmutagenic compound, the foci data could not be modeled assuming one homogeneous cell population, but was adequately fitted assuming two separate initiated cell populations that respond differently to the promotion stimulus. Other assumptions were a selective growth advantage for initiated cells during and shortly after the initiation treatment, and a transient increase of proliferation in focal hepatocytes at the first PCB administration in the higher dose groups. The model predicted an increased rate of focal cell death, at high doses, to adequately fit the foci data. These assumptions are supported by experimental data for other carcinogens, indicating the importance of studying cell kinetics in heterogeneous subpopulations of initiated cells in PCB-induced hepatocarcinogenesis.

Development of intestinal bacterial enzymes in infants--relationship to mode of delivery and type of feeding.

To evaluate the development of intestinal flora in young infants, and especially to estimate the influence of mode of delivery and type of feeding on the establishment of intestinal microflora, faecal flora was studied indirectly by measuring prospectively the faecal bacterial enzyme activities (beta-glucosidase, beta-glucuronidase and urease) in 29 full-term, healthy infants during the first 6 months of life. Mode of delivery had no influence on the faecal enzyme activities. In contrast, infants receiving formula feeds were more often urease positive at 1-2 months of age (70% vs 25%, p=0.043) and had higher median activity of beta-glucuronidase at 6 months of age (0.90 and 0.19 nmoles/mg protein x min, p= 0.0043) than exclusively breast-fed infants. Through indirect methods to measure the development of a faecal microflora our results indicate that the type of milk that infants receive during the first months of life may have an important role in the development of intestinal flora.

A new class of plant homeobox genes is expressed in specific regions of determinate symbiotic root nodules.

A cDNA containing a homeobox sequence was isolated from a soybean nodule-specific expression library. This homeobox cDNA, Ndx (nodulin homeobox), represents a small gene family with at least two members in soybean (Glycine max) and three in Lotus japonicus. One complete 3304 bp Ndx cDNA from L. japonicus encodes a protein, NDX, of 958 amino acids. An unusual type of homeodomain that differs in two of the most conserved amino acid positions in the consensus sequence is located close to the C-terminal and appears to be the only DNA-binding domain. Weak Ndx gene expression in the root increases very shortly after infection with Rhizobium and remains throughout nodule development. In situ hybridizations show cell-specific expression patterns that suggest developmentally separate regions in maturing determinate nodules. Thus in the maturing nodule Ndx and leghemoglobin genes are expressed in a mutually exclusive fashion. The Ndx transcript is also detectable in the young nodule primordium. Ndx expression is not confined to the root nodule since Ndx is also expressed in shoot and root meristems, indicating that the Ndx gene products might also be involved in developmental processes in other plant tissues.

Mode of delivery directs the phagocyte functions of infants for the first 6 months of life.

Factors that direct the immune responsiveness of the newborn beyond the immediate post-natal period are not known. We investigated the influence of mode of delivery and type of feeding on the phagocyte activity during the first 6 months of life. Sixty-four healthy infants (34 delivered vaginally and 30 by elective Caesarean section) were studied at birth and at the ages of 2 and 6 months. Phagocyte functions were studied by measuring the chemiluminescence (CL) activity of whole blood and isolated leucocytes and by investigating the expression of phagocyte receptors (FcgammaRI (CD64), FcgammaRII (CD32), FcgammaRIII (CD16), CR1 (CD35), CR3 (CD11b) and FcalphaR (CD89)) on neutrophils, monocytes and eosinophils by using receptor-specific MoAbs and immunofluorescence flow cytometry. Infants born by elective Caesarean section had significantly higher CL activity than those delivered vaginally during the entire 6-month follow up. In addition, infants who received formula feeds had significantly higher CL activity at 6 months of age and higher expression of FcgammaRI-, Fcalpha- and CR3-receptors on neutrophils than infants exclusively breast-fed. We suggest that stress reaction associated with labour influences the phagocytic activity measured in the cord blood but later during infancy the intraluminal antigens, gut microflora and diet, become important determinants in immune programming of human individuals.

Induction of altered hepatic foci by a mixture of dioxin-like compounds with and without 2,2',4,4',5,5'-hexachlorobiphenyl in female Sprague-Dawley rats.

The hepatic tumor-promoting activity of a mixture of polyhalogenated aromatic hydrocarbons (PHAHs) was studied in a medium term two-stage initiation/promotion bioassay in female Sprague-Dawley rats. The PHAH mixture contained 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 1, 2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 2,3,4,7, 8-pentachlorodibenzofuran (PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 2,3',4,4',5-pentachlorobiphenyl (PCB 118), 2,3,3',4,4', 5-hexachlorobiphenyl (PCB 156), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) and covered >90% of the total toxic equivalents (TEQ) present in Baltic herring. To determine possible interactive effects of di-ortho-substituted PCBs, the PHAH mixture was tested with (PHAH+) and without (PHAH-) PCB 153. Rats were initiated by a diethylnitrosamine injection (30 mg/kg body wt i.p.) 24 h after a partial 23 hepatectomy. Six weeks after initiation, the PHAH mixtures were administered once a week by subcutaneous injections for 20 weeks. Treatment with the PHAH mixtures caused liver enlargement and an increased activity of the hepatic cytochrome P4501A1/2 and P4502B1/2. All PHAH exposure groups exhibited an increased occurrence of hepatic foci positive for the placental form of glutathione-S-transferase. In the PHAH-group dosed 1 microgram TEQ/kg body wt/week, the volume fraction of the liver occupied by foci was significantly lower compared to the TEQ equivalent dosed TCDD group (3.8 vs 8.7%). The volume fraction was significantly increased in the groups treated with 0.5, 1, or 2 micrograms TEQ/kg body wt/week of the PHAH+ mixture (4.5, 5.2, and 6.6%, respectively) compared to the corn oil group (2.0%), but to a lower extent than expected on basis of the TEQ doses. Overall, the TEQ-based administered dose overestimated the observed tumor-promoting effects of this PHAH mixture. The applicability of the toxic equivalency factor concept, the role of differences in toxicokinetic properties and interactive effects of PCB 153 on hepatic deposition of the dioxin-like congeners are discussed.

Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery.

BACKGROUND: Newborn infants in modern maternity hospitals are subject to numerous factors that affect normal intestinal colonization--for example, cesarean delivery and antimicrobial agents. To study the duration of the effect of external factors on intestinal colonization, two groups of infants with different delivery methods were investigated. METHODS: The fecal flora of 64 healthy infants was studied prospectively. Thirty-four infants were delivered vaginally, and 30 by cesarean birth with antibiotic prophylaxis administered to their mothers before the delivery. The fecal flora was cultured on nonselective and selective media in infants 3 to 5, 10, 30, 60, and 180 days of age. Gastrointestinal signs were recorded daily by the mothers for 2 months. RESULTS: The fecal colonization of infants born by cesarean delivery was delayed. Bifidobacterium-like bacteria and Lactobacillus-like bacteria colonization rates reached the rates of vaginally delivered infants at 1 month and 10 days, respectively. Infants born by cesarean delivery were significantly less often colonized with bacteria of the Bacteroides fragilis group than were vaginally delivered infants: At 6 months the rates were 36% and 76%, respectively (p=0.009). The occurrence of gastrointestinal signs did not differ between the study groups. CONCLUSIONS: This study shows for the first time that the primary gut flora in infants born by cesarean delivery may be disturbed for up to 6 months after the birth. The clinical relevance of these changes is unknown, and even longer follow-up is needed to establish how long-lasting these alterations of the primary gut flora can be.

Methods for health risk assessment of chemicals: are they relevant for alcohol?

A description is given of the principles used for toxicological risk assessment of food additives and environmental contaminants. The terminology is not generally accepted. Hazard identification is to identify whether a substance may cause toxic effects in man. Dose-response assessment is to understand the relationship between exposure and various toxic effects. The shape of dose-response curves is discussed. For most effects (including nongenotoxic carcinogens), a threshold is assumed, under which there is no risk. For genotoxic compounds, no such threshold is assumed. For substances with a threshold, an uncertainty factor is applied to the no-observed-adverse-effect level or the lowest-observed-adverse-effect level, to arrive at an acceptable or tolerable daily intake. In the case of ethanol, some of these principles of toxicological risk assessment may be used and based on epidemiological dose-response data. The critical effects are liver effects, fetal damage, and cancer. All of these effects may be assumed to have thresholds. Possible uncertainty factors are discussed. However, because of the decreased risk of cardiovascular effects at low/moderate intakes and the fact that alcohol intake is a lifestyle factor, it is doubtful whether the application of a no-observed-adverse-effect level/uncertainty factor approach--as used for food additives and environmental pollutants, to which there is unavoidable exposure--is really applicable or meaningful for ethanol.