Biomedical subjects

P H Andersen

Publications and source records attributed to P H Andersen.

At least 19 recordsLinked to original sources

PubMed2006

The cytokine response of circulating peripheral blood mononuclear cells is changed after intravenous injection of lipopolysaccharide in cattle.

The aim of the study was to investigate lipopolysaccharide (LPS)-induced short and long term changes in capacity for intracellular cytokine-production of bovine circulating peripheral blood mononuclear cells (PBMCs). Eight dairy cows each received three intravenous injections of Escherichia coli LPS (10, 100 and 1000ng/kg, consecutively) at 3week intervals. Intracellular cytokine production was determined by flow cytometry in PBMCs obtained 0, 2, 6 and 24h after each LPS challenge. After LPS administration, proportions of monocytes producing tumour necrosis factor (TNF) alpha, interleukin (IL)-1beta and IL-8, as well as proportions of circulating lymphocytes producing interferon (IFN) gamma, decreased significantly. Within 24h, proportions had returned to or increased above pre-injection levels. Proportions of lymphocytes producing IL-4 and IL-10 increased significantly after injection of 1000ng LPS/kg. This study demonstrated that cytokine profiles shift quickly, but temporarily, to favour the anti-inflammatory response immediately after LPS exposure. The long term response to LPS was opposite to the immediate response, as cytokine profiles shifted in the 3weeks between challenges towards a pro-inflammatory response. Proportions of monocytes producing IL-1beta and TNFalpha determined immediately before the second and/or third LPS injection were higher than proportions determined before the first injection, whereas pre-injection proportions of lymphocytes producing IL-4 decreased with each challenge. These changes may result in a quicker host response to invading pathogens.

Animals↗

PubMed2006

Tissue specific distribution of the 3243A->G mtDNA mutation.

BACKGROUND: The 3243A-->G is a common pathogenic mitochondrial DNA (mtDNA) point mutation causing a variety of different phenotypes. Segregation of this mutation to different tissues during embryonic life and postnatally is still enigmatic. OBJECTIVE: To investigate the tissue distribution of this mutation. METHODS: In 65 individuals from nine families segregating the 3243A-->G mutation, the mutation load (% mutated mtDNA) was determined in various tissues. Mutation load was measured in two to four cell types--blood leucocytes, buccal cells, skeletal muscle cells, and urine epithelial cells (UEC)--derived from all three embryogenic germ layers. RESULTS: There was a significant correlation among mutation loads in the four tissues (r = 0.80-0.89, p<0.0001). With blood serving as reference, the mutation load was increased by 16% in buccal mucosa, by 31% in UEC, and by 37% in muscle. There were significant differences between the mitotic tissues blood, buccal mucosa, and UEC (p<0.0001), but no difference between UEC and muscle. Using the present data as a cross sectional investigation, a negative correlation of age with the mutation load was found in blood, while the mutation load in muscle did not change with time; 75% of the children presented with higher mutation loads than their mothers in mitotic tissues but not in the post-mitotic muscle. CONCLUSIONS: There appears to be a uniform distribution of mutant mtDNA throughout the three germ layers in embryogenesis. The significant differences between mutation loads of the individual tissue types indicate tissue specific segregation of the 3243A-->G mtDNA later in embryogenesis.

Adolescent↗

PubMed2004

Spontaneously reported adverse reactions after diphtheria-tetanus revaccination at 4-6 years of age--a comparison of two vaccines with different amounts of diphtheria toxoid.

On 1 January 1996, diphtheria-tetanus revaccination at the age of 5 years was implemented in the Danish Childhood Vaccination Programme. Initially, a combined DT vaccine containing 25 Lf diphtheria toxoid was used. Due to a high frequency of spontaneously reported adverse reactions, however, concerns were raised that the diphtheria dose was too high, and it was reduced to 6.25 Lf. This survey presents the rates of spontaneously reported adverse reactions following diphtheria-tetanus revaccinations of 4-6-year-old from 1996 to 2002. The change to the lower dose of diphtheria toxoid resulted in a remarkable reduction in the yearly rates of injection site reactions: in 1996, the rate was 180 injection site reactions per 100,000 vaccinations; from 1998 to 2002, this changed to between 12 and 24 reactions per 100,000 vaccinations. Furthermore, the rates of systemic reactions such as fever were reduced.

Child, Preschool↗

PubMed2004

Acute phase protein concentrations in serum and milk from healthy cows, cows with clinical mastitis and cows with extramammary inflammatory conditions.

The concentrations of the two acute phase proteins, serum amyloid A and haptoglobin, in serum and milk were compared in 10 cows with clinical mastitis, 11 cows with extramammary inflammatory conditions and 10 clinically healthy control cows. The concentrations of both acute phase proteins were higher in the serum and milk of the cows with mastitis than in the cows in the other two groups. Four of the cows with extramammary inflammatory conditions had serum amyloid A concentrations in serum above 100 microg/ml, but negligible concentrations in milk, indicating that a pathogen must be present in the mammary gland for serum amyloid A to accumulate in milk. The acute phase protein concentrations in milk increased significantly with increasing somatic cell count, suggesting that they may be indicators of the severity of an infection.

Animals↗

PubMed2004

Selectivity of (3)H-MADAM binding to 5-hydroxytryptamine transporters in vitro and in vivo in mice; correlation with behavioural effects.

1. Binding of the novel radioligand (3)H-2-(2-dimethylaminomethyl-phenylsulphanyl)-5-methyl-phenylamine ((3)H-MADAM) to the serotonin transporter (SERT) was used to characterise a range of selective serotonin re-uptake inhibitors (SSRIs) in vitro and in vivo. 2. (3)H-MADAM bound with high affinity in a saturable manner to both human SERT expressed in CHO cells (K(d)=0.20 nm (pK(d)=9.74+/-0.12), B(max)=35+/-4 fmol mg(-1) protein) and mouse cerebral cortex membranes (K(d)=0.21 nm (pK(d)=9.66+/-0.10), B(max)=50+/-24 fmol mg(-1) protein). 3. Binding of (3)H-MADAM was highly selective for SERT in vitro as demonstrated by the in vitro profile of MADAM tested at 75 different receptors, ion channels and transporters. This was further substantiated by the pharmacological profile of the binding. Hence, the binding of (3)H-MADAM was potently inhibited by SSRIs but not by selective inhibitors of noradrenaline transport and dopamine transport. Likewise, a 5-HT(2A/2C) receptor antagonist did not inhibit (3)H-MADAM binding. 4. (3)H-MADAM binding in vivo was inhibited only by compounds which also inhibited the binding of (3)H-MADAM in vitro (the SSRIs, mixed SERT/noradrenaline transport inhibitors and clomipramine), confirming the selectivity of (3)H-MADAM for SERT also in vivo. Moreover, compounds effective in inhibiting (3)H-MADAM binding were the only ones found to be active in the mouse 5-HTP potentiation test confirming the model as a behavioural correlate to in vivo 5-HT uptake. 5. Finally, it was found that a SERT occupancy of 85-95% was necessary to produce 50% of the maximum behavioural response (ED(50)).

5-Hydroxytryptophan↗

PubMed2004

Tuberculosis not verified by culture in a low incidence country.

The objective was to evaluate the magnitude, diagnostic basis and characteristics of patients notified with tuberculosis (TB) not verified by culture. All patients in Denmark notified with TB between 1995 and 1999 were identified through the national TB register. Nationwide culture results were obtained from the International Reference Laboratory of Mycobacteriology. The proportion of culture verification decreased from 91% in 1995 to 80% in 1999. A total of 2518 patients were notified, of which 374 (14.9%) were not verified by culture. For 80 (3.2%) patients no specimens were submitted. Instead the diagnosis was mainly based on X-ray (72.6%) for patients with pulmonary TB and histology (38.3%) for patients with extrapulmonary TB. For 216 patients aged 0-14 y, 74 (34.3%) were not verified by culture. The proportion of TB not verified by culture in Denmark is low compared to other European countries. Some cases may be well explained, e.g. children with a close contact suffering from TB or patients with extrapulmonary TB with limited number of specimens. However, for a minority group of patients with pulmonary TB there were no obvious reasons why specimens were not submitted for culture. Culture verification should remain a priority when possible.

Adolescent↗

PubMed2004

Acute bovine laminitis: a new induction model using alimentary oligofructose overload.

Twelve dairy heifers were used to examine the clinical response of an alimentary oligofructose overload. Six animals were divided into 3 subgroups, and each was given a bolus dose of 13, 17, or 21 g/kg of oligofructose orally. The control group (n = 6) was sham-treated with tap water. Signs of lameness, cardiovascular function, and gastrointestinal function were monitored every 6 h during development of rumen acidosis. The heifers were euthanized 48 and 72 h after administration of oligofructose. All animals given oligofructose developed depression, anorexia, and diarrhea 9 to 39 h after receiving oligofructose. By 33 to 45 h after treatment, the feces returned to normal consistency and the heifers began eating again. Animals given oligofructose developed transient fever, severe metabolic acidosis, and moderate dehydration, which were alleviated by supportive therapy. Four of 6 animals given oligofructose displayed clinical signs of laminitis starting 39 to 45 h after receiving oligofructose and lasting until euthanasia. The lameness was obvious, but could easily be overlooked by the untrained eye, because the heifers continued to stand and walk, and did not interrupt their eating behavior. No positive pain reactions or lameness were seen in control animals. Based on these results, we conclude that an alimentary oligofructose overload is able to induce signs of acute laminitis in cattle. This model offers a new method, which can be used in further investigation of the pathogenesis and pathophysiology of bovine laminitis.

Acidosis↗

PubMed2004

Dose dependency and individual variability of the lipopolysaccharide-induced bovine acute phase protein response.

In order to investigate the dose dependency and the individual variability of the lipopolysaccharide (LPS)-induced acute phase protein response in cattle, 8 nonlactating, nonpregnant Danish Holstein cows were challenged 3 times each by intravenous injection of increasing doses (10, 100, and 1000 ng/kg, consecutively) of Escherichia coli LPS with 3-wk intervals. All 3 LPS doses resulted in a rapid increase in serum concentrations of haptoglobin and serum amyloid A (SAA) and a decrease in serum concentrations of albumin in all 8 cows. Serum concentrations of acute phase proteins (APP) remained altered for several days after each LPS injection, and their increase or decrease was significantly related to LPS dose. In addition to dose dependency, the response was also dependent on the individual, as APP concentrations differed significantly among cows. To compare APP production in 2 consecutive challenges, individual APP levels after the challenge with 100 ng LPS/kg were correlated to levels attained after the challenge with 1000 ng LPS/kg. Serum amyloid A concentrations correlated between the 2 challenges, whereas haptoglobin concentrations tended to correlate; no correlation could be demonstrated between SAA and haptoglobin concentrations in either of the challenges, which suggests that the synthesis of haptoglobin and SAA are regulated in different ways. In conclusion, cattle are highly susceptible to LPS, as very low doses of LPS elicited acute phase albumin, SAA, and haptoglobin responses. Concentrations of APP not only reflect the magnitude of LPS exposure but are also influenced by the ability of the individual cow to mount an acute phase response. The ability to produce SAA and haptoglobin may be an innate characteristic of the individual, as responses in consecutive challenges were quantitatively similar.

Acute-Phase Proteins↗

PubMed2003

Potential for improving description of bovine udder health status by combined analysis of milk parameters.

The objective of this study was to assess the potential of a stepwise multivariate procedure to quantify cow-level udder health based on eight milk parameters: milk yield, protein percentage, fat percentage, lactose percentage, citrate percentage, somatic cell count (SCC), and two electrical conductivity parameters. The data were collected in one research herd and included 821 cow-level observations. In addition to milk parameters, disease recordings and bacteriology on quarter milk samples every eighth week throughout lactation were included. A multivariate mixed model was applied to the milk parameters in a healthy subset to adjust for the following systematic factors: total mixed ration (TMR) energy density, breed-line combination, parity, stage of lactation, and season. The proportion of variance accounted for by the mixed model ranged from 0.14 to 0.82 depending on milk parameter. The adjustments estimated in the healthy subset were applied to the whole dataset, including observations pertaining to nonhealthy cows. Combined description of the adjusted variation in the milk parameters was performed with a principal component analysis. The first principal component (Prin1) described 30% of the adjusted variation and was interpreted as being the main consequences of mastitis. Finally, cluster analysis based on Prin1 separated the observations into nine clusters, which were strongly associated with udder health in terms of increasing clinical and subclinical mastitis with increasing level of Prin1. It was concluded that a multivariate approach to assess udder health from milk parameters has the potential to substantially improve description of udder health.

Analysis of Variance↗

PubMed2002

Application of a 5' nuclease assay for detection of Lawsonia intracellularis in fecal samples from pigs.

A 5' nuclease assay was developed to detect Lawsonia intracellularis in porcine fecal samples. The specific probe and primers were chosen by using the 16S ribosomal DNA gene as a target. The 5' nuclease assay was used with a total of 204 clinical samples, and the results were compared to those of immunohistochemistry (IM) on ileal sections of the same animals. There was 91% agreement between the results of IM and the 5' nuclease assay. In the 5' nuclease assay, 111 (54%) of the pigs tested positive for L. intracellularis infection, with a mean cycle threshold (Ct) value of 27.2, whereas 98 (48%) of the pigs tested positive by IM. On average, the Ct and DeltaRn values for the positive samples were 27.2 (standard deviation [SD], 3.7) and 1.6 (SD, 0.7), respectively. A Ct value of 27.2 corresponds to a fecal excretion of approximately 10(7) L. intracellularis cells per g of feces. Furthermore, a total of 40 fecal samples derived from a herd known to be free from infection with L. intracellularis all tested negative, with a Ct value of 40. By using a Ct value of 36 as the cutoff limit, the detection limit of the assay was 1 L. intracellularis cell per PCR tube. In conclusion, the 5' nuclease assay that has been developed represents an applicable fast method for detection of L. intracellularis in fecal samples, with a sensitivity and specificity comparable to those of IM.

Animals↗

PubMed2001

[Tuberculosis among children in Denmark, 1990-1999].

INTRODUCTION: During a century with a decreasing incidence of tuberculosis (TB) in Denmark, the last 15 years have seen an increase. We describe the epidemiology of TB in children in Denmark with the focus on the impact of immigration. MATERIALS AND METHODS: Data from the national TB surveillance of 1990-1999 were analysed. The variables were age, gender, nationality, TB location(s), and the results of microscopy and culture. RESULTS: Three hundred and forty-nine children below 15 years of age were found, representing 8% of all notified cases of TB. Of these, 268 children (78%) were immigrants. The number of children increased over time, as did the proportion of immigrants (p < 0.0001). The median age was four years in the native Danes and nine years in the immigrant children (p < 0.001). The mean annual incidence of TB in the children was 3.9 per 10(5); 45.8 per 10(5) in the immigrants and 0.92 per 10(5) in the native Danes. The incidence increased from 2.0 in 1990 to 5.3 per 10(5) in 1999. Forty-nine per cent of the immigrants were Somalis, 13% were Pakistanis. The mean annual TB incidence was 581 per 10(5) in Somalis and 78 per 10(5) in Pakistanis. The incidence increased with age in children from Pakistan and Somalia and decreased in native Danes. Seventy-seven per cent of native Danes and 65% of immigrants had pulmonary TB +/- other locations (p < 0.05). Sixty-seven per cent of immigrant children with extrapulmonary TB had TB in the glands, 9% had TB in the bones, and another 9% had TB in the digestive system, proportions that were 38% (p < 0.05), 8%, and 0%, respectively, in native Danes. DISCUSSION: Immigration has had an impact on the incidence of TB, as well as on the pattern of TB location in children in Denmark. The incidence was 48 times higher in immigrant than in native Danish children.

Child↗

PubMed2001

The growth hormone-releasing hormone receptor: desensitisation following short-term agonist exposure.

We have investigated the effect of short-term preexposure of growth hormone-releasing hormone (GHRH) on the subsequent response to GHRH in a baby hamster kidney (BHK) cell line expressing the human GHRH receptor and in primary rat pituitary cells. In the BHK cells the receptor was rapidly desensitised in a homologous fashion. Preexposure with agents directly stimulating the cAMP pathway like forskolin and db-cAMP had no effect. In rat pituitary cells we also observed a rapid desensitisation of the GHRH response in an apparently homologous fashion. In both systems the desensitisation was dose-dependent with no change in the potency of the hormone in a subsequent stimulation, only the efficacy was decreased. In the rat pituitary cell, the response measured as growth hormone release was more sensitive to the agonist-induced desensitisation than the cAMP response. No indication of depletion of growth hormone (GH) stores was seen. In rat pituitary cells, contrary to observations in BHK cells, preexposure with both forskolin and db-cAMP desensitised a subsequent growth hormone-releasing hormone stimulation, indicating a heterologous desensitisation. Phorbol-12-myristate 13-acetate (PMA), on the other hand, had no effect. In the baby hamster kidney cells it was demonstrated that the GHRH receptor surface expression decreased following preexposure with GHRH. This phenomenon was observed only in whole cells suggesting a rapid internalisation process. Together, these data indicate that after short-term GHRH preexposure, both in a human and rat system, the following GHRH response is desensitised. In BHK cells this desensitisation is strictly homologous. In rat pituitary cells, on the other hand, the desensitisation is a mixed homologous/ heterologous type.

Adenylyl Cyclases↗

PubMed1999

Development of a site-directed polyclonal antibody against the pituitary growth hormone-releasing hormone receptor and its use to estimate GHRH receptor concentration in normal and hypothyroid rats.

A site-directed polyclonal antipeptide antibody was generated in rabbits against segment 392-404 of the rat pituitary growth hormone-releasing hormone receptor (GHRH-R), using a multiple antigenic peptide system strategy of immunization. This C-terminal intracellular region of the rat GHRH-R exhibits 85% sequence identity with the human GHRH-R. The purified anti-GHRH-R(392-404) IgGs were characterized in cell lines expressing the human GHRH-R and in rat and human anterior pituitary, using immunoblotting. The polyclonal antibody recognized a 45-kD protein in human GHRH-R-transfected BHK 570 cell membrane preparations but not in wild-type cells. A 45-kD N(alpha)-tagged human GHRH-R was immunodetected with both antitag and anti-GHRH-R antibodies in human GHRH-R-transfected HEK 293 cells. Cross-linking of [(125)I-Tyr(10)]hGHRH(1-44)NH(2) to GHRH-R-transfected BHK cells led to the detection of a major and specific 45-kD radioactive complex. Its probing with the anti-GHRH-R(392-404) IgGs led also to the detection of a 45-kD entity. In rat anterior pituitary homogenates or membrane preparations, immunoblotting led to the detection of 44-, 47- and 65-kD proteins. In human anterior pituitary membrane preparations, immunoblotting led to the detection of 52- and 55-kD proteins. No immunoreactive signal was observed in the rat liver. Cross-linking of [(125)I-Tyr(10)]hGHRH(1-44)NH(2) to rat anterior pituitary homogenates revealed the presence of specific 28-, 47- and 65-kD radioactive complexes. Probing of these radioactive complexes with the anti-GHRH-R(392-404) IgGs resulted in the visualization of 28-, 47- and 65-kD entities and of an additional immunoreactive 44-kD protein. To assess the usefulness of this GHRH-R antibody, estimation of changes in the concentration of rat anterior pituitary GHRH-R was performed by immunoblotting and compared to binding data after a 3-week antithyroid treatment. The treatment known to depress the 2.5- and 4-kb GHRH-R mRNA transcripts by at least 1.7-fold decreased the apparent maximal concentration of high (B(max1)) and low (B(max2)) affinity binding sites by 4.6- and 15.2-fold, respectively, and the 47- and 65-kD GHRH-R proteins by 3.5- and 1. 25-fold, respectively. Altogether, the characteristics of the anti-GHRH-R(392-404) polyclonal antibody indicate that it specifically recognizes the human and rat GHRH-R. It also represents an additional valuable tool to estimate variations of GHRH-Rs in physiopathological conditions known to affect GHRH-R mRNA and/or GHRH binding site concentrations.

Animals↗

PubMed1999

Pharmacological characterisation of a new oral GH secretagogue, NN703.

NN703 is a novel orally active GH secretagogue (GHS) derived from ipamorelin. NN703 stimulates GH release from rat pituitary cells in a dose-dependent manner with a potency and efficacy similar to that of GHRP-6. The effect is inhibited by known GHS antagonists, but not by a GH-releasing hormone antagonist. Binding of (35)S-MK677 to the human type 1A GHS receptor (GHS-R 1A) stably expressed on BHK cells was inhibited by GHRP-6 and MK677 as expected. NN703 was also able to inhibit the binding of (35)S-MK677. However, the observed K(i) value was lower than expected, as based on the observed potencies regarding GH release from rat pituitary cells. Similarly, the effect of NN703 on the GHS-R 1A-induced inositol phosphate turnover in these cells showed a lower potency, when compared with GHRP-6 and MK677, than that observed in rat pituitary cells. The effect of i.v. administration of NN703 on GH and cortisol release was studied in swine. The potency and efficacy of NN703 on GH release were determined to be 155+/-23 nmol/kg and 91+/-7 ng GH/ml plasma respectively. A 50% increase of cortisol, compared with basal levels, was observed for all the tested doses of NN703, but no dose-dependency was shown. The effect of NN703 on GH release after i. v. and oral dosing in beagle dogs was studied. NN703 dose-dependently increased the GH release after oral administration. At the highest dose (20 micromol/kg), a 35-fold increase in peak GH concentration was observed (49.5+/-17.8 ng/ml, mean+/-s.e.m.). After a single i.v. dose of 1 micromol/kg the peak GH plasma concentration was elevated to 38.5+/-19.6 ng/ml (mean+/-s.e.m.) approximately 30 min after dosing and returned to basal level after 360 min. The oral bioavailability was 30%. The plasma half-life of NN703 was 4.1+/-0.4 h. A long-term biological effect of NN703 was demonstrated in a rat study, where the body weight gain was measured during a 14-day once daily oral challenge with 100 micromol/kg. The body weight gain was significantly increased after 14 days as compared with a vehicle-treated group. In summary, we here describe an orally active and GH specific secretagogue, NN703. This compound acts through a similar mechanism as GHRP-6, but has a different receptor pharmacology. NN703 induced GH release in both swine and dogs after i.v. and/or p.o. administration, had a high degree of GH specificity in swine and significantly increased the body weight gain in rats.

Administration, Oral↗

PubMed1998

A new series of highly potent growth hormone-releasing peptides derived from ipamorelin.

A new series of GH secretagogues derived from ipamorelin is described. In an attempt to obtain oral bioavailability, by reducing the size and the number of potential hydrogen-bonding sites of the compounds, a strategy using the peptidomimetic fragment 3-(aminomethyl)benzoic acid and sequential backbone N-methylations was applied. Several compounds from this series release GH with high in vitro potency and efficacy in a rat pituitary cell assay and high in vivo potency and efficacy in anesthetized rats. The tetrapeptide NNC 26-0235 (3-(aminomethyl)benzoyl-D-2Nal-N-Me-D-Phe-Lys-NH2) shows, following iv administration, comparable in vivo potency to ipamorelin, GHRP-2, and GHRP-6 with an ED50 in swine at 2 nmol/kg. NNC 26-0235 demonstrated a 10% oral bioavailability in dogs, and NNC 26-0235 and ipamorelin were able to increase basal GH level by more than 10-fold after oral administration of a dose of 1.8 and 2.7 mg/kg, respectively. The tripeptide NNC 26-0323 (3-(aminomethyl)benzoic acid-N-Me-D-2Nal-N-Me-D-Phe-ol) which showed moderate in vitro potency but lacked in vivo potency demonstrated a 20% oral bioavailability in rats.

Administration, Oral↗

PubMed1998

Novel orally active growth hormone secretagogues.

A novel class of growth hormone-releasing compounds with a molecular weight in the range from 500 to 650 has been discovered. The aim of this study was to obtain growth hormone secretagogues with oral bioavailability. By a rational approach we were able to reduce the size of the lead compound ipamorelin (4) and simultaneously to reduce hydrogen-bonding potential by incorporation of backbone isosters while retaining in vivo potency in swine. A rat pituitary assay was used for screening of all compounds and to evaluate which compounds should be tested further for in vivo potency in swine and oral bioavailability, fpo, in dogs. Most of the tested compounds had fpo in the range of 10-55%. In vivo potency in swine after iv dosing is reported, and ED50 was found to be 30 nmol/kg of body weight for the most potent compound.

Administration, Oral↗

PubMed1998

Decreased muscle strength in patients with alcoholic liver cirrhosis in relation to nutritional status, alcohol abstinence, liver function, and neuropathy.

To study motor function quantitatively in alcoholic liver cirrhosis muscle strength, liver function, peripheral nerve function, and nutrition were assessed in 24 patients. Isokinetic strength of flexion and extension at elbow, wrist, hip, knee, and ankle and of shoulder abduction and adduction was evaluated and compared with findings in 24 matched healthy subjects. Degree of liver disease was assessed with the Child-Pugh score and the galactose elimination capacity (GEC). Nutritional status was evaluated with an estimation of lean body mass (LBM) from 24-hour urinary creatinine excretions. Peripheral nerve function was evaluated with neurological symptom and disability scores, nerve conduction studies, and quantitative sensory tests summed to obtain a neuropathy rank-sum score (NRSS) for each patient. Combined muscle strength at hip, knee, ankle, shoulder, elbow, and wrist were weakened with 34% (P < .005), 35% (P < .001), 35% (P < .01), 34% (P < .01), 29% (P < .01), and 29% (P < .02), respectively. The median Child-Pugh score was 7 (range, 5-12), and the median duration of alcohol abstinence was 90 days (range, 5-960 days). After multiple linear regression analysis including LBM, Child-Pugh score, GEC, duration of alcohol abstinence, and NRSS, only LBM was correlated to the strength at the knee (r=.79; P < .0001) and at the ankle (r=.63; P < .01). It is concluded that muscle strength is weakened substantially in alcoholic patients with liver cirrhosis and that weakness is related to the severity of malnutrition but not to the severity of liver disease, duration of alcohol abstinence, or neuropathy.

Adult↗

PubMed1998

Skin symptoms in patients with atopic dermatitis using enzyme-containing detergents. A placebo-controlled study.

Detergent enzymes may cause skin irritation and occasionally hypersensitivity reactions. The potential hazards of these enzymes have led some physicians to advise atopic dermatitis patients against the use of enzyme-enriched detergents. A three-phased randomised, double-blind, cross-over experiment was designed to question this recommendation. Each period was of 1 month's duration. In the first phase patients continued using their normal washing detergent. In phase II patients used trial detergent with or without added enzymes, and during phase III patients were given the opposite trial detergent. A total of 25 patients completed the study. The primary efficacy parameters were inter-period changes in corticosteroid usage and changes in SCORAD. Secondary efficacy parameters were altered subjective symptoms scored during the final 2 weeks of each interval. Analyses of all data revealed no statistical differences in any of the primary or secondary parameters comparing treatment and placebo periods. Our data therefore seem to exclude that atopic dermatitis may exacerbate during 1 month's exposure to enzyme-enriched detergents. Since no significant irritant capacity was detected in atopic dermatitis patients, it is unlikely that consumers with "normal skin" will experience any skin discomfort when enzyme-enriched detergents are used.

Adolescent↗