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Biomedical subjects

L G Hansen

Publications and source records attributed to L G Hansen.

At least 55 records · Page 3Linked to original sources

PCB congeners in the rat brain: selective accumulation and lack of regionalization.

Perturbations in the developing nervous system have been associated with perinatal exposures to polychlorinated biphenyls (PCBs). It remains unclear whether these neurotoxic effects are direct or secondary to other toxic processes. This study was designed to determine which PCB congeners accumulate in the brain as a result of perinatal exposure and if this accumulation is regionally specific. Sprague-Dawley rat dams were dosed by gavage with corn oil or Aroclor 1242 in corn oil (4 or 16 mg/kg/d) on d 10-16 of gestation. At weaning (d 21), one male and one female pup from each litter were euthanatized and three specific regions of the brain (frontal cortex, hippocampus, and caudate putamen) were collected for PCB analysis by gas chromatography. Ten peaks, which represent 10-14 PCB congeners, were detected in all samples. There were no differences in PCB concentration between sexes or among brain regions, but the different congeners differed from each other in degree of bioaccumulation. Brain PCB concentrations increased with increased dose for all congeners except PCB 28 (2,4,4'), which was present at a higher concentration in the lower dose-group. To characterize regionalization of PCBs in the brain further, weanling rats were dosed intravenously with [14C]-PCB 77 (3,3',4,4'-tetrachlorobiphenyl; 0.25 microCi/g; 2.0 micrograms/g) or [14C]-PCB 47 (2,2',4,4'-tetrachhlorobiphenyl; 0.25 microCi/g; 5.3 micrograms/g) in dimethyl sulfoxide (DMSO). Rats were killed after 72 h and the brains were quickly removed and frozen on dry ice. The brains were serially sectioned on a cryostat and the sections (16 microns) subjected to autoradiography (3-5 mo of exposure). The radioactivity was homogeneously distributed in the brain tissue for both PCBs. PCB 77-treated, but not PCB 47-treated, pups showed increased activity in areas with blood vessels present. This was consistent with differences in the blood-brain ratios for PCB 47 and PCB 77, which were determined to be 0.44 and 16.8, respectively.

Animals↗

Effects of perinatal exposure to specific PCB congeners on thyroid hormone concentrations and thyroid histology in the rat.

Time-mated Sprague-Dawley rats were exposed to PCB 28 (2,4,4'-trichlorobiphenyl), 8 or 32 mg/kg/day; PCB 118 (2,3',4,4',5-pentachlorobiphenyl), 4 or 16 mg/kg/day; or PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl), 16 or 64 mg/kg/day. At weaning, serum thyroxine (T4) was markedly depressed in pups, but not dams, exposed to PCB 118 or 153. Triiodothyronine (T3) was unchanged in pups and dams. In a histological evaluation of thyroids, the PCB 118 pups revealed changes suggestive of sustained TSH stimulation, including increased follicular cell vacuolization and height, increased nuclear vesiculation, and decreased colloid area. Decreases in body and brain weights and increases in liver weights were observed in some groups, with the high dose PCB 118 pups showing the greatest effect.

Animals↗

Prediction of allergy from family history and cord blood IgE levels. A follow-up at the age of 5 years. Cord blood IgE. IV.

Screening of total IgE in 1189 cord blood samples was conducted by Phadebas IgE PRIST in a one-year birth cohort 1983-1984 in Viborg, Denmark. 113 children with cord blood IgE levels > or = 0.5 kU/l and 138 children chosen at random among those with cord blood IgE levels < 0.5 kU/l were seen at a follow-up at 5 years of age. Based upon history and physical examination a diagnosis of definite atopy or no atopy was established. Allergy (IgE mediated) was defined as atopic disease combined with increased total IgE levels at 5 years of age. The cumulative prevalence of atopic disease was not influenced by cord blood IgE levels or atopic predisposition. Cord blood IgE levels had a low sensitivity as a predictor of atopic disease. A statistically significant correlation between serum levels of IgE at birth and at 5 years was however found (p < 0.001), and a significantly greater number of children with elevated cord blood IgE levels developed allergic disease before 5 years of age (p < 0.01). A cut-off limit of 0.3 kU/l was superior to the originally suggested limit of 0.5 kU/l. A total IgE level > 63 kU/l (geometric mean + 1 SD) at the age of 5 years can be regarded as being an elevated level. A cord blood IgE level > or = 0.3 kU/l in combination with atopic predisposition was predictive of allergic disease, especially allergic bronchial asthma. With regard to allergic disease, the positive predictive value was 26%, the sensitivity 33% and the rate ratio for development of allergic disease 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Safety of a new, ultrafiltrated whey hydrolysate formula in children with cow milk allergy: a clinical investigation.

The purpose of this study was to determine whether a new ultrafiltrated whey hydrolysate infant formula, Profylac, could be administered safely to children with cow milk protein allergy/intolerance. Profylac has a stated molecular weight of < 8 kD and at least 30,000 times reduced antigenicity which is controlled by a combination of ELISA-techniques and immunochemical methods. The study comprised 66 children with cow milk protein allergy/intolerance diagnosed by controlled elimination/challenge procedures. The children were aged 1 month-14.5 years, median 1 11/12 years and 15 were below 1 year. Thirty-five of these children had proven IgE-mediated reactions (cow milk protein allergy). Sixty-one of the children had at least two different symptoms and 31 had concomitant allergies to other foods and/or inhalants. All 66 children underwent and tolerated open, controlled challenges with Profylac. A total of 64 children continued having Profylac daily for at least 3 months and 58 for at least 6 months after challenge. Nine of the children older than 1 year did not like the taste and only had Profylac in minor amounts. No side effects were registered. Fifteen of the infants were below 1 year of age, and this group was compared with an age matched group of 16 infants challenged with and fed an extensively hydrolysed casein hydrolysate, Nutramigen. All the infants in these two groups accepted and tolerated Profylac and Nutramigen, respectively, and no side effects were registered. Among the 35 patients with IgE-mediated reactions 6% (2/35) had positive skin prick tests and 11% (3/28) had specific IgE class 2 against Profylac, 2 of the latter before intake of Profylac.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Preventive effect of feeding high-risk infants a casein hydrolysate formula or an ultrafiltrated whey hydrolysate formula. A prospective, randomized, comparative clinical study.

In a prospective study of a 1-year birth cohort of 158 high-risk infants the effect of feeding breastmilk, a casein hydrolysate (Nutramigen) or a new ultrafiltrated whey hydrolysate (Profylac) on the development of cow milk protein allergy/intolerance (CMPA/CMPI) was assessed and compared. All the infants had biparental or severe single atopic predisposition, the latter combined with cord blood IgE > or = 0.5 kU/L. At birth all infants were randomized to Nutramigen or Profylac, which was used when breastfeeding was insufficient or not possible during the first 6 months of life. During the same period this regimen was combined with avoidance of solid foods and cow milk protein. All mothers had unrestricted diets and were encouraged to do breastfeeding only. Moreover, avoidance of daily exposure to tobacco smoking, furred pets and dust-collecting materials in the bedroom was advised. The infants were followed prospectively from birth to 18 months of age. All possible atopic symptoms were registered and controlled elimination/challenge studies were performed when symptoms suggested CMPA/CMPI. A total of 154 (97%) were followed up and 141 followed the diet strictly. Eighty-eight (62%) of the infants were breastfed for at least 6 months, 20 (14%) were breastfed exclusively, 59 and 62 had varying amounts of Nutramigen or Profylac respectively. CMPA/CMPI was diagnosed in 1/20, 1/59 and 3/62 in the breastfed, the Nutramigen and Profylac groups respectively, but 1 of the latter also had Nutramigen. None of the infants showed reactions against Nutramigen or Profylac. In 4 infants symptoms were provoked by breastmilk when the mother ingested cow milk and in 1 only by cow milk.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Feeding↗

Modification by polychlorinated biphenyls (PCBs) of cadmium induced lesions in the planarian model, Dugesia dorotocephala.

The appearance of abnormal growths on the planarian, Dugesia dorotocephala, in response to cadmium with and without pre-exposure to L-buthionine-R, S-sulfoximine (BSO) and concurrent exposure to the polychlorinated biphenyls (PCBs) Aroclor 1254, PCB 28, PCB 110 or PCB 126 is described. Pigmented rose thorn (PRT) lesions were non-invasive and appeared in response to PCBs. Post-head (PH) lesions developed in up to 100% of the animals within 6-20 days post-dosing, progressed rather rapidly and were highly invasive. Round tail tip (RTT) lesions appeared in lower frequencies within 10-30 days, but progressed extremely rapidly resulting in tail loss within 48 h. We have referred to these types of lesions as "tumors", but they are not necessarily characteristic of vertebrate neoplasms. PCBs interacted with cadmium in a complex way, in some cases increasing total lesions and decreasing time-to-lesion and in other cases having the opposite effects. A three-factor (PCB, PCB dose, Cd dose) nested analysis of variance model was used to determine lesion rates in order to compare PCB potencies as potentiators or antagonists. The Aroclor mixture was always the least potent co-toxicant but appeared to be the most potent antagonist; the coplanar PCB 126 was the most potent co-toxicant. The complex response surfaces and the lack of stoichiometry in dose-response relationships indicate that multiple mechanisms are responsible for PH and RTT lesions in planarians. These results emphasize the complexity of PCB toxicities and suggest further studies to validate the planarian model as a screen for combinations or environmental mixtures which may have altered biological potency in other species.

Animals↗

[Ultrasonically guided Biopty-biopsy of focal liver processes].

During a period of three years, 51 patients with focal hepatic changes were submitted to 55 ultrasonically guided Biopty-biopsies. Histological diagnoses could be established in 45 patients at the first biopsy which corresponds to a diagnostic certainty of 88.2% Histological diagnoses were established in 49 patients which corresponds to a certainty of 96%. The frequency of complications was 3.9%. Biopty-biopsy is recommended as a good method because it is easy to carry out and provides just as good results as other methods of biopsy. In addition, it can provide more histological information than aspiration biopsies which are, however, somewhat cheaper.

Adult↗

Effect of an allergy prevention programme on incidence of atopic symptoms in infancy. A prospective study of 159 "high-risk" infants.

A total of 105 "high-risk" infants born in 1988 were studied prospectively from birth to 18 months of age. The infants were recommended breastfeeding and/or hypoallergenic formula (Nutramigen or Profylac) combined with avoidance of solid foods during the first 6 months of life. All mothers had unrestricted diet. Avoidance of daily exposure to tobacco smoke, furred pets and dust-collecting materials in the bedroom were advised. This prevention group was compared with a control group consisting of 54 identically defined "high-risk" infants born in 1985 in the same area. All infants had either severe single atopic predisposition combined with cord blood IgE > or = 0.5 KU/l or biparental atopic predisposition. The control group had unrestricted diet and was not advised about environmental factors. Apart from the prevention programme and year of birth the prevention group and the control group were comparable. The parents were highly motivated and compliance was good. The rate of participation was 97%, and 85% followed the dietary measures strictly. The cumulative prevalence of atopic symptoms was significantly lower at 18 months in the prevention group (32%), as compared with the control group (74%) (p < 0.01), due to reduced prevalence of recurrent wheezing (13% versus 37%; p < 0.01), atopic dermatitis (14% versus 31%; p < 0.01), vomiting/diarrhoea (5% versus 20%; p < 0.01) and infantile colic (9% versus 24%; p < 0.01). The cumulative prevalence of food allergy was significantly lower in the prevention group (6% versus 17%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cohort Studies↗

Cord blood IgE. I. IgE screening in 2814 newborn children.

Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985-1986) in Denmark (n = 1189 + 1625). 48.6% of the sera contained less IgE than the detection limit 0.1 kU/l. Cord blood IgE values greater than or equal to 0.5 kU/l were regarded as elevated. 13.2% of the sera contained at least 0.5 kU/l of IgE, with a significant preponderance in boys. Geometric mean cord blood IgE was 0.13 kU/l and 0.12 kU/l, respectively. Geometric mean cord blood IgE was significantly higher in boys. A significant seasonal variation with lowest IgE values in the autumn was found. No correlation between cord blood IgE and birth weight or gestational age was demonstrated. Only few newborns had cord blood IgA values greater than 0.014 g/l, calculated as geometric mean cord blood IgA + 2 SD among children with no detectable cord blood IgE, indicating infrequent contamination with maternal blood.

Cohort Studies↗

Cord blood IgE. II. Prediction of atopic disease. A follow-up at the age of 18 months.

Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985-1986) in Denmark (n = 1189 + 1625). For follow-up we chose all infants with cord blood IgE greater than or equal to 0.5 kU/l and a randomly chosen group of the same size with cord blood IgE less than 0.5 kU/l. A total of 762 infants were clinically evaluated at 18 months of age. A diagnosis of definite atopy, probable atopy or no atopy, including both IgE and non-IgE mediated disease was established. Applying different cord blood IgE cut-off values (0.3, 0.5, 0.8, 1.1) we did not find an excess of atopic infants among those with elevated cord blood IgE irrespective of the chosen cut-off value. Atopic predisposition or family history of atopic disease was defined as at least one parent or older sibling with atopic disease. Significantly more infants with a family history developed atopy at 18 months. In the 2 series the positive predictive values of cord blood IgE greater than or equal to 0.5 were 43% and 46% and the sensitivities were 17% and 15%. The predictive values of having a family history were 48% and 44% and the sensitivities were 55% and 58%.

Cohort Studies↗

Cord blood IgE. III. Prediction of IgE high-response and allergy. A follow-up at the age of 18 months.

Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985-1986) in Denmark (n = 1189 + 1625). For follow-up we chose all infants with cord blood IgE greater than or equal to 0.5 kU/l and a randomly chosen group of the same size with cord blood IgE less than 0.5 kU/l. A total group of 762 infants were clinically evaluated at 18 months of age, and in 688 of these we evaluated total and specific IgE. A diagnosis of definite atopy, probable atopy or no atopy was established. In the present study we defined allergic disease as atopic disease combined with elevated total IgE. We found a statistically significant correlation between cord blood IgE and IgE at 18 months of age. Significantly more infants with elevated cord blood IgE had developed allergic disease at 18 months. A cut-off value of 0.3 kU/l for cord blood IgE was superior to the originally suggested 0.5 kU/l. Significantly more infants with elevated cord blood IgE had developed specific IgE antibodies at 18 months. The most frequent specific IgE antibody was towards cow's milk. Specific IgE antibodies were very rarely found when total IgE was not elevated. A total IgE at the age of 18 months greater than 26 kU/l could be regarded as elevated. With regard to allergic disease the positive predictive values of cord blood IgE greater than or equal to 0.3 kU/l in the 2 series were 21% and the corresponding sensitivities 67% and 46%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prognosis in postoperative discitis. A retrospective study of 111 cases.

111 cases of postoperative discitis during 1968-1986 were analyzed retrospectively. The diagnosis was confirmed by lumbar tomography. Low back pain appeared at an average of 16 days postoperatively. Laboratory findings were of minor value in the diagnosis since elevated ESR, white blood cell count, and body temperature were inconstant findings. Compared with a matched control group, there was a higher incidence of chronic low back pain and vocational handicap in the discitis patients. There was no difference in the consumption of analgetics, the subjective evaluation of the final outcome, spinal mobility or neurologic findings.

Adult↗

A scientific basis for proposed quality assurance of a new screening method for tumor-like growths in the planarian, Dugesia dorotocephala.

Various abnormal growths appear on planarians, Dugesia dorotocephala, during and after exposure to polychlorinated biphenyls (PCBs) 28, 110, and 126; Aroclor 1254; cadmium sulfate; and L-buthionine-(R,S)-sulfoximine (BSO). Daily observations under magnification were used to describe the location, development, and morphology of three different types of tumor-like growths ("tumors"). "Post-head tumors" were found to be highly invasive, progressive, and lethal to the animal depending on concentrations and combinations of the compounds used. Survivors from post-head tumors exhibited aberrant morphogenesis, but developmental abnormalities were eventually shed. Post-head tumors occurred within 2 weeks of initial exposure, while "round tail tip tumors" appeared after 2-3 weeks. The rate of progression and invasiveness was greater for the round tail tip tumors. "Pigmented rose thorn tail tumors" occurred in low incidence (4-20%) and appeared to be harmless and noninvasive, requiring months to develop from the first appearance of pigmentation. The aggressive, proliferative, and invasive characteristics of post-head and round tail tip tumors are analogous to those of malignant tumors, while pigmented rose thorn tumors were benign. High dose of cadmium alone were sufficient to initiate the post-head and round tail tip tumors. PCBs potentiated the tumorigenicity of low cadmium doses and enhanced the very low spontaneous incidence of pigmented rose thorn tumors. PCBs also impaired motor activity, causing the graceful gliding locomotion to be replaced by a twisting serpentine movement accompanied by muscular dystrophy. In addition, high (50 micrograms) doses of PCB 110 depressed activity, while lower (5 micrograms) doses and 50 micrograms Aroclor 1254 induced restlessness and enhanced locomotion. These data provide the basis for quality assurance.

Animals↗