Search PubMed⌕ Search

Biomedical subjects

J Holt

Publications and source records attributed to J Holt.

At least 55 records · Page 3Linked to original sources

Impact of pollution and place of residence on atopic diseases among schoolchildren in Telemark County, Norway.

For estimation of the prevalence, degree of severity, and association with outdoor pollution, a questionnaire on asthma and other atopic diseases was distributed to the parents of 4666 7-13-year-olds, comprising all the children in 36 schools in Telemark County, Norway, including 37% of the schoolchildren in the county. The response rate was 94%. In a validity study employing clinical evaluations, the questionnaire-based diagnosis of asthma was found to have a sensitivity of 0.96 and a specificity of 0.88. The lifetime prevalence of asthma in Telemark was 9% (boys 11.3%, girls 6.6%; p < 0.001). There was no significant difference in the lifetime prevalence of asthma by pollution zone; 8.3% in heavily, 9.3% in moderately, and 9.2% in minimally polluted zones. The asthma prevalence was significantly higher (14.2%; p < 0.05) among boys in the coastal area of the county than in the mountainous area (8.9%). Both of these areas were in the minimal pollution zone. Of asthma cases, 67% were categorized as mild, 29% as moderate, and 4% as severe. The lifetime prevalence was 17.8% (boys 21.3%, girls 14.2%; p < 0.001) for allergic rhinitis, 13.2% (boys 11.4%, girls 15.2%; p < 0.001) for atopic eczema, and 29.6% (boys 31.7%, girls 27.4%; p < 0.01) for overall atopic disease (asthma, allergic rhinitis, eczema). These findings are not compatible with the hypothesis that outdoor pollution is associated with the lifetime prevalence of asthma in school-age children. The results also show that less than 0.5% of schoolchildren suffer from severe asthma.

Adolescent↗

Thyroid-induced changes in the growth of the liver, kidney, and diaphragm of neonatal rats.

Eu-, hypo- and hyper-thyroid rats were studied 12 days postpartum. Hypothyroidism was induced by administering propylthiouracil (PTU) via the mother's drinking water between late gestation and throughout lactation. This procedure effectively blocked the normal early postnatal surge of T3 and T4. In contrast, hyperthyroidism was induced in the young pups by daily injections of T4 from day 3 postpartum. The effects of these experimental manipulations of thyroid status on the rates of protein turnover and growth of the liver, kidney, and diaphragm were studied and compared with measurements made on appropriate euthyroid control tissues. Tissue rates of protein synthesis were decreased in response to hypothyroidism with consequent growth retardation of all three tissues and the whole animal. In contrast, the three body tissues responded very differently to the induction of hyperthyroidism. Hepatic rates of protein synthesis and growth were completely unaffected by thyroid excess. The response of the diaphragm was essentially the reverse of that seen with hypothyroidism, i.e., the enhanced rates of protein synthesis and protein degradation leading to muscle hypertrophy. The rates of protein turnover in the kidney were also increased, but unlike the diaphragm the net result was renal atrophy. Clearly, thyroid hormones influence the normal rapid growth of the neonate and its individual tissues. However, beyond a certain concentration the threshold of responsiveness to these hormones seems to vary between individual tissues.

Animals↗

C1 inhibitor and diagnosis of hereditary angioedema in newborns.

Symptoms of hereditary angioedema may present during the child's first years. Attacks may be a particular threat to the narrower airway of the child. An early diagnosis is most valuable because effective C1 inhibitor (C1 INH) concentrate is available. We present a reference area for the antigenic and functional determination of C1 INH by using uncontaminated umbilical cord blood from 80 normal newborns collected by puncturing vessels in the newly delivered placenta. We examined two full-term babies (1 and 2) from mothers with hereditary angioedema type I the same way. The concentration of C1 INH antigen was determined by radial immunodiffusion. The C1 INH functional assay was based on the addition of a known quantity of C1s, which enzymatically splits a chromogenic substrate. The test was performed in the presence of methylamine and heparin in a kinetic microtiter plate assay. Citrated plasma was used in both assays. The data obtained in the 80 cord blood samples (2.5-97.5 percentile) were 0.11-0.22 g/L for C1 INH antigen (adults, 0.15-0.33 g/L) and 47.2-85.9% for C1 INH function (percentage of adults). In cord blood, baby 1 had an antigenic value of 0.12 g/L (7.5 percentile) and C1 INH function of 61.8% (42 percentile). The corresponding values for baby 2 in cord blood were less than 0.05 g/L (0.106 g/L < 2.5 percentile) and 34.3% (12.9% < 2.5 percentile). Baby 2 had markedly lower C4 values yet much higher C4 activation products than baby 1. At 4 mo, baby 1 had an antigenic C1 INH value of 0.24 g/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioedema↗

Classroom attributes and achievement test scores for deaf and hard of hearing students.

This study examined reading comprehension and mathematics computation achievement of deaf and hard-of-hearing students in a variety of school settings. Data were collected by Gallaudet University's Center for Assessment and Demographic Studies during its 1990 standardization of the 8th Edition Stanford Achievement Test. Descriptive and inferential statistical methods were used to analyze the relationships among achievement scores, classroom attributes, and demographic factors associated with achievement. Based on the results of this study, inclusion with hearing students in regular classrooms is related to a variety of demographic factors. When reading comprehension and mathematics computation scores are adjusted for these factors, they are higher for the deaf and hard-of-hearing students in regular classrooms. However, it is not known whether the higher achievement is due to inclusion or whether students were selected for inclusion due to their higher achievement levels.

Achievement↗

The influence of thyroid hormones on the growth of the atria and ventricles of the heart in immature rats.

The normal plasma concentrations of tri-iodothyronine (T3) and thyroxine (T4) increase approximately six- and fourfold respectively between the end of gestation and weaning in the rat. This early postnatal surge of thyroid hormones was experimentally modified to produce either a state of hypo- or hyperthyroidism. The growth and rates of protein turnover in the atria and ventricles of the heart were studied, 12 and 20 days postpartum, both as a function of age and of changing thyroid status. Neonatal hypothyroidism was induced by adding propylthiouracil to the mothers' drinking water late in gestation and throughout lactation. Hyperthyroidism was achieved by giving the suckling pups daily injections of T4 from day 3 postpartum onwards. Between 12 and 20 days the weight and protein mass of the combined ventricles of the euthyroid animals approximately doubled, along with substantial increases (50%) in the RNA and DNA contents. Over this same 8 days, growth in the combined atria was much slower. During the same period, hypothyroidism significantly retarded the growth of these immature rats and their atria and ventricles. Both the rates of protein synthesis and protein degradation were decreased in the atria and ventricles. In contrast, hyperthyroidism significantly increased growth in both types of cardiac tissue, this being more pronounced in the atria than in the ventricles between 12 and 20 days. The rates of protein synthesis were increased accordingly, principally by increases in the ribosomal activities. In conclusion, thyroid hormones clearly influence the early postnatal growth of the atria and ventricles of the heart in the rat.

Aging↗

[Neonatal respiratory distress syndrome treated with a natural surfactant. The Norwegian Curosurf study].

43 Norwegian premature infants with respiratory distress syndrome were randomized to receive either a high dose (initial dose 200 mg/kg) or a low dose (initial dose 100 mg/kg) of natural porcine surfactant (Curosurf). In the high dose group, up to five doses of surfactant could be given compared with three in the low dose group. In the high dose group, oxygen requirement was significantly lower during the first 36 hours after surfactant was administered than the requirement in the low dose group. There was no difference in outcome between the high and low dose groups. Outcome was poor for babies with birthweight < 750 gram or gestational age < 26 weeks, in spite of an initial favourable surfactant response in several of them. We conclude that the initial dose of Curosurf should be 100 mg/kg and two more doses can be given if necessary.

Biological Products↗

Optimization of a recombinant von Willebrand factor fragment as an antagonist of the platelet glycoprotein Ib receptor.

The binding of von Willebrand factor (vWF) to platelet glycoprotein (GP) Ib receptor is one of the initial events in thrombus formation. Previous studies have shown that RG12986, a reduced and alkylated recombinant fragment of vWF (Ser445-Val733), can inhibit binding of native vWF to GP Ib and offers potential as an anti-thrombotic agent. We have now evaluated a series of deletion mutants of RG12986 and found that reduced and alkylated rvWF508-704 is close to the minimal sequence with optimal RG12986-like activity (IC50 for inhibition of GP Ib-dependent platelet aggregation in the absence of modulators: 0.022 microM +/- 0.01, n = 3) and that it too binds directly to GP Ib. Under in vitro conditions, with no exogenous modulators present and in the absence of shear stress, oxidized rvWF508-704 (containing a disulfide bond between Cys508 and Cys659) is approximately 5-fold less active than reduced and alkylated rvWF508-704; the two fragments, however, display comparable activity in the presence of the modulator botrocetin. The smaller rvWF508-704 fragment offers distinct advantages over RG 12986. In particular, removal of non-active NH2 and COOH terminal sequences may reduce the risk of antigenicity and may contribute to rendering the molecule mostly monomeric in solution, as opposed to the monomer-dimer equilibrium previously described for RG12986.

Chromatography, High Pressure Liquid↗

Adult neuronal ceroid lipofuscinosis presenting with psychiatric symptoms: a case report.

OBJECTIVE: Psychiatric symptoms can occur early in the course of neurodegenerative metabolic conditions like Kufs' disease. This report is an illustration of a case where the diagnosis was considered primarily psychiatric till MRI (magnetic resonance imaging) of the brain was found abnormal. METHOD: A case of adult neuronal ceroid lipofuscinosis (NCL) or Kufs' disease in a 24 year old white female who presented with phobic symptoms, behavioral changes, thought disorder and depressed mood prior to the onset of seizures is reported. She was referred to psychiatry for further treatment. We report the various features of the case including the peculiar finding in the MRI of the head. RESULTS: The MRI finding was unique in that it revealed extensive cortical gray matter lesions. This finding led to further investigations. Kufs' disease was diagnosed following a brain biopsy. The MRI finding is noteworthy because it is not typical of previously published cases. The patient was treated with tegretol mainly to control seizures. The overall prognosis seemed poor since patient showed break through seizures in two months. CONCLUSIONS: Clinicians should consider neurological or medical conditions and pursue further investigations in psychiatric patients when they concurrently or later develop subtle neurologic symptoms, idiopathic seizures or cognitive deficits.

Adult↗

The influence of thyroid hormones on the growth of the lungs in perinatal rats.

The growth and rates of protein turnover in the perinatal lung have been studied in the rat during normal development between late gestation and weaning, and after altering their thyroid status. The aim was to establish what influence thyroid hormones have on the early stages of growth in the lungs. Perinatal hypothyroidism was induced by administering propylthiouracil (PTU) via the mothers' drinking water from late gestation and throughout lactation. A precocious and elevated surge of thyroid hormones was induced by daily injections of T4 from day 3 postpartum onwards. Hypothyroidism in the neonate, but not the fetus, significantly retarded the growth of the animal and its lungs. This was attributable to a decrease in both the pulmonary rates of protein synthesis and protein degradation; the effect on the former rate exceeding that on the latter. Neonatal hyperthyroidism did not significantly alter protein turnover or the growth of the lungs, compared with euthyroid control tissues. This contrasts with the accelerated growth of some other body tissues in the presence of excess thyroid hormones.

Animals↗

Immunologic effects of ursodeoxycholic acid in primary biliary cirrhosis.

Investigations were undertaken to determine the effect on lymphocyte reactivity of treatment of primary biliary cirrhosis with ursodeoxycholic acid (UDCA). Eight patients with stage 2 and 6 with stage 3 primary biliary cirrhosis were observed. Patients were treated with 300 mg of UDCA three times daily for 1 to 3 years. UDCA reduced jaundice, pruritus, and serum alkaline phosphatase levels. Repeat liver biopsy showed a decrease in inflammation in 3 patients. One patient with stage 3 primary biliary cirrhosis had disease progression despite UDCA treatment. Phytohemagglutinin (PHA) and concanavalin A (con A) were added to mixed lymphocytes from 9 patients receiving UDCA before and after 1 year of treatment. T-cell reactivity was determined by evaluating tritiated thymidine incorporation into DNA. Patients exhibiting an improvement in liver function tests had a significant reduction in lymphocyte reactivity to these mitogens (P < .01). When UDCA was stopped, the response to PHA and con A returned to pretreatment levels, reflecting continued presence of immunologic abnormalities characteristic of primary biliary cirrhosis. UDCA's effect on lymphocyte reactivity appears to be due to a reduction of hydrophobic bile acids, since it does not alter response to mitogens in patients with a normal liver.

Adult↗

Casemix classification and Australian doctors. Risks and opportunities.

"Casemix" is an information tool--a set of patient care classifications and ideas about their use. It is useful only if it promotes understanding, and leads to better performance of the health system. Here we discuss some uses of casemix classifications, including payment of hospitals on a per case basis. Clinicians need to be concerned about both the design of casemix classifications themselves, and the ways in which they are used.

Australia↗

Estrogen and progesterone withdrawal increases cerebral vasoreactivity to serotonin in rabbit basilar artery.

An in vitro animal model which examines the effects of sex hormone variations during the menstrual cycle on basilar artery reactivity is presented. Three groups of rabbits were utilized: a chronically depleted control group which received no further hormonal treatment after bilateral surgical oophorectomy (O), simulating menopause, and two groups of intact females, one of which was treated to mimic the estrogen and progesterone surge during the luteal phase (H) and the third group which was acutely estrogen and progesterone depleted after the luteal surges to simulate the immediate premenstrual state (W). We show that both acute and chronic estrogen and progesterone withdrawal significantly increase serotonin sensitivity (ED50) in basilar artery rings. There was no difference between groups for maximum contraction (Tmax) to serotonin, nor optimal resting tension. Furthermore, there was no difference in vasoreactivity and contractility to norepinephrine between groups. In order to distinguish between the effects of chronic and acute treatment we examined acute estrogen and progesterone superfusion in basilar artery rings from intact non-treated female rabbits. Acute superfusion of pre-contracted and non-pre-contracted artery segments resulted in significant dilatation only when supraphysiologic concentrations of estrogen and progesterone were used. We conclude that both acute and chronic female sex hormone withdrawal selectively increases cerebral vasoreactivity to serotonin.

Animals↗

The effects of established diabetes on the growth of the fetal liver and skin in the rat.

1. The effects of uncontrolled maternal diabetes on the growth of the whole rat fetus and its liver and skin were studied over the last 4 days of gestation. 2. Smaller fetuses, with growth-retarded livers and skins, were consistently found between 18 and 21 days in the diabetic pregnancies. 3. The smaller diabetic livers and skins (i.e. combined epidermis and dermis) possessed lower protein, RNA and DNA contents, compared with the same fetal tissues from normal pregnancies. 4. The growth retardation of the livers in diabetic fetuses was attributed to fewer normally sized hepatic cells. 5. Whilst hepatic rates of protein synthesis (measured in vivo) remained largely unchanged, these were actually increased in the skin, compared with normal control tissues. 6. These findings point to an elevated rate of protein degradation in both diabetic tissues as the most likely cause of their retarded growth.

Animals↗

Production and functional characterization of a recombinant fragment of von Willebrand factor (vWF): an antagonist to platelet receptor GP Ib.

We expressed a recombinant peptide fragment (Ser445-Val733) of human von Willebrand factor (vWF), containing the binding domain for the platelet receptor of GP Ib, in E. coli. This 33 kD peptide blocks binding of the intact vWF molecule to GP Ib in the presence of modulators. Thus, it offers potential as an antithrombotic agent. High level expression was achieved in a plasmid construct driven by the bacteriophage T7 promoter. The peptide was solubilized from inclusion bodies in strong chaotrope, then reduced and alkylated. Following purification, formulation at pH 3.5, and lyophilization, the reconstituted experimental product (RG 12986) exists as an equilibrium of monomer and dimer species. When formulated above pH 5.0, soluble aggregates are formed; these solutions have less bioactivity than RG 12986. Interestingly, the non-aggregated state of RG 12986 remains conserved following dilution and incubation with platelet-poor plasma. The overall purification/low pH formulation strategies may be applicable to other E. coli recombinant proteins having a tendency to aggregate following removal of chaotrope near physiologic pH when in a concentrated format.

Cloning, Molecular↗