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Biomedical subjects

E Young

Publications and source records attributed to E Young.

At least 73 records · Page 4Linked to original sources
PubMed1997

Compositae sensitivity and chronic hand dermatitis in a seven-year-old boy.

Compositae dermatitis is rare in childhood, with few cases documented in the literature. We report a 7-year-old boy who presented with a dermatitis mainly affecting his dominant hand. Patch testing revealed contact sensitivity to sesquiterpene lactone (SL) mix, and subsequent testing with Compositae oleoresins showed sensitivity to daisy, dandelion and chrysanthemum. The dermatitis improved on avoidance of handling plants. We have not documented any other cases of Compositae sensitivity in 187 other children, aged under 16 years, who have undergone patch testing with SL mix between 1992 and 1996 in our department. This case illustrates that Compositae sensitivity may present with a localized dermatitis and that, although uncommon, sensitization may occur in early childhood.

Allergens↗
PubMed1997

Transient leukaemia cutis in chronic lymphocytic leukaemia.

Leukaemia cutis arises due to cutaneous infiltration of neoplastic leukocytes or their precursors. Recent evidence suggests that this sign does not necessarily herald a poor prognosis. We describe a 72-year-old woman with B-cell chronic lymphatic leukaemia (CLL) who developed a papular eruption on her breast at the site of a recent herpetic eruption. Histology and immunostaining showed a dense dermal B-cell infiltrate in keeping with leukaemia cutis. The papules cleared in 6 months without treatment, leaving atrophic scars. The histological features and possible aetiological mechanisms of post-herpetic papular eruptions in CLL are reviewed.

Aged↗
PubMed1997

Transient leukaemia cutis in chronic lymphocytic leukaemia.

Leukaemia cutis arises from cutaneous infiltration by neoplastic leukocytes or their precursors. Recent evidence suggests that this sign does not necessarily herald a poor prognosis. We describe a 72-year-old woman with B-cell chronic lymphatic leukaemia who developed a papular eruption of her breast at the site of a recent herpetic eruption. Histology and immunostaining showed a dense dermal B-cell infiltrate in keeping with leukaemia cutis. The papules cleared in 6 months without treatment, leaving atrophic scars. The histological features and possible aetiological mechanisms of post-herpetic papular eruptions in chronic lymphatic leukaemia are reviewed.

Aged↗
PubMed1997

Fucosidosis: genetic and biochemical analysis of eight cases.

The molecular basis of the deficiency of alpha-L-fucosidase has been investigated in eight patients who had been diagnosed clinically and enzymatically as suffering from the autosomal recessive lysosomal storage disease fucosidosis. None of the patients had a deletion or gross alteration of the alpha-L-fucosidase gene (FUCA1). Single strand conformation polymorphism (SSCP) analysis followed by direct sequencing of amplified exons and flanking regions identified putative disease causing mutations in six of the patients, who had severe forms of the disease and very low residual alpha-L-fucosidase activity and protein. They were a 10 bp deletion in exon 1 (E113fs), a 1 bp deletion at position -2 of intron 2 (S216fs), a g-->a transition at IVS5+1, point mutations W183X and N329Y in exons 3 and 6, respectively, and a compound allele consisting of a point mutation in the signal peptide in exon 1, P5R, and a 1 bp insertion in exon 6 (Y330fs). One patient in whom an SSCP change was not detected had residual alpha-L-fucosidase activity and cross reacting protein in the heterozygous range and normal metabolism of metabolites containing fucose in his fibroblasts, consistent with the low activity polymorphism. The eighth patient, who had a partial deficiency of alpha-L-fucosidase in her fibroblasts and leucocytes at a young age but normal alpha-L-fucosidase activity and protein at a later age, was homozygous for the common Q281R polymorphism in exon 5. She had no other sequence changes and Kivlin (Peters plus) syndrome has subsequently been diagnosed. The basis of her transient deficiency of alpha-L-fucosidase is not known. The detection of five novel mutations in six severely affected patients confirms the genetic heterogeneity in fucosidosis.

Adult↗
PubMed1997

Induction of the acute-phase reaction increases heparin-binding proteins in plasma.

We have previously demonstrated that the nonspecific binding of unfractionated heparin (UFH) to plasma proteins has a marked modulating effect on its anticoagulant activity. Since some heparin-binding proteins are also acute-phase-reactant proteins, we explored the possibility that the induction of the acute-phase response can increase the plasma concentrations of heparin-binding proteins. The recovery of a fixed amount of UFH or low-molecular-weight heparin (LMWH) added in vitro to rat plasma samples obtained at various time intervals after the administration of intravenous endotoxin or subcutaneous turpentine was compared with that of saline-treated control animals. The anti-factor Xa activity was measured in the plasma samples before and after the addition of a chemically modified low-affinity heparin (LAH) to displace the proportion of the added heparin that is reversibly bound to plasma proteins. Our results show that at 6 hours post-endotoxin and at 24 hours post-turpentine treatment, virtually no anti-factor Xa activity could be measured in the plasma samples, while the expected levels were obtained for control plasma. After the addition of LAH to displace protein-bound UFH, essentially the same anti-factor Xa levels were measured in the plasma from all three treatment groups. These results indicate that induction of the acute-phase reaction can dramatically increase the levels of heparin-binding proteins in rat plasma. In addition, we compared the anti-factor Xa recovery of UFH with that of an LMWH from the plasma of endotoxin- and saline-treated rats and demonstrated that LMWH binds less to plasma proteins than UFH, even in plasma in which the levels of heparin-binding proteins are markedly elevated. The recovery of a fixed amount of UFH added in vitro to human plasma from septic patients was also reduced, but not to the same extent as seen in rat plasma. Removal of candidate heparin-binding and acute-phase proteins by immunodepletion indicated that vitronectin plays an important role in the nonspecific binding of UFH in patient plasma.

Acute-Phase Reaction↗
PubMed1997

Trial of two bandaging systems for chronic venous leg ulcers.

A four-layer bandaging system developed at Charing Cross Hospital has been found to be effective in healing chronic venous ulcers but is not available on the Drug Tariff. An alternative system was devised from bandages available on the Drug Tariff and a community-based randomised controlled trial was undertaken to compare the two systems. Twenty-nine patients with a total of 35 ulcerated legs were recruited. Equal numbers of ulcerated legs healed using the two compression systems. Nineteen ulcerated legs did not heal, of which six were withdrawn from the trial-two in the trial system and four in the Charing Cross system. Of the 13 remaining ulcerated legs, for which treatment was completed, the mean reduction in ulcer area was 34% with the trial system and 39% with the Charing Cross system. The change in ulcer area was not statistically significant. However, a much larger trial is required in order to demonstrate definitively that the two bandaging systems are equivalent.

Bandages↗
PubMed1997

Skin dose reduction by a clinically viable magnetic deflector.

A variable magnetic deflector which attaches onto the treatment head of a linear accelerator has reduced skin dose by as much as 65% for 6MV x-rays. The magnetic deflector is constructed from Neodymium Iron Boron (NdFeB) rare earth magnets. It weighs approximately 15 kg and is designed to easily fit onto the accessory mount of a clinical linear accelerator. All field sizes are attainable up to 35 cm x 35 cm at 100 cm SSD. The gap between the magnetic poles can be adjusted, providing the highest field strength for each field size. Magnetic field strengths up to 0.55 Tesla are attainable. For a 6MV x-ray beam with a 10 mm perspex block tray, surface dose is reduced from 29% to 14% and from 59% to 37% for a 20 cm x 20 cm and 35 cm x 35 cm field size, respectively. Results at varying SSD's have shown at least 10 cm of space must be allowed between the magnets and patient for adequate reduction of skin dose through removal of electron contaminants.

Humans↗
PubMed1996

Histomorphometric analysis of the effects of standard heparin on trabecular bone in vivo.

Long-term heparin treatment causes osteoporosis through an as yet undefined mechanism. To investigate this phenomenon, we treated rats with once daily subcutaneous injections of heparin (in doses ranging from 0.25 to 1.0 U/g) or saline for 8 to 32 days and monitored the effects on bone both histomorphometrically and by serial measurements of urinary type 1 collagen cross linked-pyridinoline (PYD) and serum alkaline phosphatase, markers of bone resorption and formation, respectively. Histomorphometric analysis of the distal third of the right femur in the region proximal to the epiphyseal growth plate showed that heparin induces both a time- and dose-dependent decreased in trabecular bone volume, with the majority of trabecular bone loss occurring within the first 8 days of treatment. Thus, heparin doses of 1.0 U/g/d resulted in a 32% loss of trabecular bone. Heparin-treated rats also showed a 37% decrease in osteoblast surface as well as a 75% decrease in osteoid surface. In contrast, heparin treatment had the opposite effect on osteoclast surface, which was 43% higher in heparin-treated rats, as compared with that in control rats. Biochemical markers of bone turnover showed that heparin treatment produced a dose-dependent decrease in serum alkaline phosphatase and a transient increase in urinary PYD, thus confirming the histomorphometric data. Based on these observations, we conclude that heparin decreases trabecular bone volume both by decreasing the rate of bone formation and increasing the rate of bone resorption.

Alkaline Phosphatase↗
PubMed1996

Age, sex, and the familial risk of rheumatoid arthritis.

The familial aggregation of rheumatoid arthritis was examined to determine factors modifying the risk of rheumatoid arthritis in first degree relatives of 165 cases ascertained from January 1, 1987, through March 31, 1987, using the Saint Margaret Memorial Hospital Rheumatoid Arthritis Registry, Pittsburgh, Pennsylvania, without regard to previous information concerning the occurrence of rheumatoid arthritis among their family members. The reported affection status of first degree relatives, verified through a structured clinical evaluation, revealed a false-positive reporting rate for family members of 61%. In contrast, there were no false-negative cases detected. There were no differences in average family size or total number of years at risk between 135 simplex and 30 multiplex families; however, aggregation analysis revealed that only 18 of 30 confirmed multiplex families had significant excess risk of rheumatoid arthritis. Significant differences were found when probands from multiplex families were compared with those from simplex families with regard to female to male ratio for probands (1:1 in multiplex families vs. 3:1 in simplex families) and average age of onset for probands (41 years in multiplex families vs. 48 years in simplex families). The familial risk for rheumatoid arthritis was similar in parents (4.2%) and siblings (4.6%) and lowest for children (0.7%) of probands. The authors assert that the affection status of first degree relatives of patients with rheumatoid arthritis is often falsely reported as positive. The familiality of rheumatoid arthritis may be more accurately related to the sex and age at onset of the affected family member.

Adult↗
PubMed1996

Comparison of propofol versus thiopentone with midazolam or lidocaine to facilitate laryngeal mask insertion.

PURPOSE: To assess the ease of insertion of laryngeal mask airway (LMA) comparing propofol with lidocaine or midazolam followed by thiopentone and compare the costs with each technique. METHODS: One hundred and fifty ASA 1 or 2 patients equally divided into three groups scheduled for elective surgery were recruited into this prospective, single blind, randomized, parallel groups study. Anaesthetic induction was achieved with 1 microgram.kg-1 fentanyl i.v. followed by either 2.5 mg.kg-1 propofol (group P), or a sequence of 1.5 mg.kg-1 lidocaine and 5 mg.kg-1 thiopentone (group LT), or midazolam 0.1 mg.kg-1 and, three minutes later, 5 mg.kg-1 thiopentone (group MT). The LMA was inserted by the blinded anaesthetist who assessed and graded the conditions for LMA insertion and noted any adverse responses (i.e., inadequate jaw relaxation, gagging, coughing, limb or head movement, hiccough and laryngospasm). Conditions were considered "excellent" if there were no adverse responses, and "satisfactory" if such a response was mild and transient. RESULTS: Excellent or satisfactory conditions were observed in 48 (96%) patients in the midazolam-thiopentone group, 46 (92%) in the propofol group, and 34 (68%) in the lidocaine-thiopentone group (P = 0.0001). The incidence of gagging (P = 0.042), limb movement (P = 0.031), and laryngospasm (P = 0.0001) was higher in the lidocaine-thiopentone group. CONCLUSIONS: With the above doses, a fentanyl-midazolam-thiopentone combination which is about 35% less expensive than fentanyl-propofol, provides equally good conditions for the insertion of LMA.

Adult↗
PubMed1996

Psychiatric aspects of food-related physical symptoms: a community study.

Beliefs about symptoms, food and health, mood disturbance, consulting behavior, and eating habits and attitudes were assessed by postal questionnaire in 273 adults who complained of food intolerance in a community study. In contrast to previous studies conducted in allergy clinics, most subjects who reported symptoms related to foods that were judged not to be allergic on clinical grounds did not manifest significant mood disturbance, impaired social adjustment, or excessive consultation for other nonspecific physical or psychological symptoms. Subjects attributing symptoms to food sensitivity suffered less psychological impairment than those attributing symptoms to other causes such as stress, stomach or bowel disorder, or food contamination. However, an important subgroup of patients did report marked impact of symptoms on everyday life, frequent consultation in traditional and complementary medical contexts, and appreciable mood disturbance. The reported association between perceived food intolerance and psychiatric disorder in allergy clinic patients is likely to be an artifact of referral bias.

Adult↗
PubMed1996

Effects of misoprostol and prostaglandin E2 on proteoglycan biosynthesis and loss in unloaded and loaded articular cartilage explants.

The effects of misoprostol, a prostaglandin E1 analog, and prostaglandin E2 on proteoglycan biosynthesis and loss were studied in unloaded and mechanically loaded mature bovine articular cartilage explants. The prostaglandins were administered daily at dosages of 0, 10, 100 and 1000 eta g/ml for up to seven days, and proteoglycan biosynthesis determined by measurement of radiolabelled sulfate incorporation. The presence of misoprostol lead to a significant (p < 0.001) dose-dependent inhibition (30%-50%) in proteoglycan biosynthesis which was also dependent on exposure time (p < 0.05). A significant decrease in biosynthesis (34%) was also found for prostaglandin E2, but only at the highest dose (1000 eta g/ml). Proteoglycan catabolism rates were not affected by either substance as assessed by loss of newly synthesized proteoglycan. The application of a continuous cyclic mechanical compressive load (stress of 1.0 MPa at 1 hertz for 24 hours) resulted in a significant inhibition of proteoglycan biosynthesis (up to 50%) as compared to unloaded explants. However, there was no additive effect when mechanical load and misoprostol or prostaglandin E2 were combined. These results suggest that prostaglandins may have a role in the degenerative and repair process in various forms of arthritis where elevated intra-articular levels of prostaglandin E2 are present.

Animals↗
PubMed1996

Sialosyl-Tn antigen is prevalent and precedes dysplasia in ulcerative colitis: a retrospective case-control study.

BACKGROUND & AIMS: Expression of the carbohydrate-associated sialosyl-Tn (STn) antigen has been correlated with carcinogenesis in sporadic colon cancer. This retrospective study analyzed surveillance colonoscopy biopsy specimens to determine whether STn antigen could serve as a marker for neoplasia risk in patients with long-standing ulcerative colitis. METHODS: Eleven patients who developed dysplasia or cancer and who had undergone at least three surveillance colonoscopies were matched with 11 controls who had not developed neoplasia. Sections from 969 available surveillance biopsy specimens were stained immunohistochemically with monoclonal antibody TKH2 and were interpreted blindly. RESULTS: Compared with controls, patients expressed STn antigen more frequently in their biopsy specimens (44% patient biopsy specimens vs. 11% control biopsy specimens). Patients were also more likely to undergo colonoscopies with two or more colonic segments expressing STn antigen (73% vs. 22%), repeated STn antigen expression in two or more consecutive colonoscopies (91% vs. 27%), and STn antigen expression proximal to the hepatic flexure (64% vs. 0%). STn antigen appearance preceded the detection of neoplasia by 7 or fewer years, and its preferential expression in patients was not confounded by the degree of active inflammation. CONCLUSIONS: Repeated STn antigen expression in nondysplastic colonic mucosa may presage the development of neoplasia in long-standing ulcerative colitis and may be a useful adjunct to dysplasia during colonoscopic surveillance.

Adult↗
PubMed1996

The effect of adding a surfeit of autologous CD8+ T cells to SCID mice after secondary rexenografts of Graves' thyroid tissue.

To investigate the effect of adding a surfeit of CD8+ T cells as a potential immunoregulator in Graves' disease (GD), thyroid tissues from 4 patients with GD and 2 normal subjects (N) were initially xenografted into nude mice. Eight weeks after xenografting, the thyroid tissues, which were then devoid of lymphocytes and appeared normal, were retrieved from the nude mouse, and rexenografted (rexenografts) into severe combined immuno-deficient (SCID) mice; 20 x 10(6) of autologous peripheral blood mononuclear cells (PMBC) or 20 x 10(6) of CD8(+)-depleted PBMC ("non-CD8 cells," i.e., CD4-enriched PBMC) were simultaneously engrafted into SCID mice with thyroid rexenografts. In addition, 20 x 10(6) of CD8(+)-enriched PBMC ("CD8-doubled" cells, which were prepared to double the percentage of CD8+ T cells compared to that of PBMC) were engrafted into SCID mice with rexenografts from 2 GD and 2 N; finally, 20 x 10(6) of PBMC plus an extra 10 x 10(6) of CD8+ T cells ("extra-CD8 added" cells, total 30 x 10(6) of CD8-enriched cells) were engrafted into separate SCID mice with rexenografts from 2 GD. The reengraftment of GD rexenografts or N rexenografts alone did not result in the detection of thyroperoxidase (TPO)-antibodies (Abs), thyroglobulin (Tg)-Abs, thyroid-stimulating Ab (TSAb) production, human IgG, or lymphocytic infiltration in the xenografts. However, the engraftment of either autologous PBMC or non-CD8 cells from patients with GD and N into SCID mice with rexenografts caused human IgG to become detectable and then rise further in 10 of 17 SCID mice; when human IgG, TPO-Ab, Tg-Ab, and TSAb were quantitated, GD rexenografts plus non-CD8 cells engrafted into SCID mice showed a higher production of each antibody and human IgG than in GD rexenografts plus PBMC, or GD rexenografts plus CD8-doubled cells, or GD rexenografts plus extra "CD8-added" cells. Moreover, when CD8-doubled cells or extra CD8-added cells with rexenografts were engrafted to SCID mice with rexenografts, they showed generally lower production of human IgG and thyroid antibodies compared to SCID mice into which PBMC were engrafted with rexenografts, despite the fact that 50% more cells (30 x 10(6)) were engrafted in the preparations of extra CD8-added cells. In conclusion, CD8+ T cells from patients with GD appeared to suppress the induction of thyroid antibodies, TSAb, and human IgG. The CD8+ cells thus are acting as suppressor or regulatory T cells. Such cells might be important in the pathogenesis of autoimmune thyroid disease.

Animals↗
PubMed1995

IL-6 stimulates vitronectin gene expression in vivo.

We tested the hypothesis that vitronectin (Vn) is regulated as an acute phase reactant in response to inflammatory stimuli. In initial experiments, Vn levels were measured during the surgically induced acute phase response in humans. The plasma concentration of Vn increased approximately twofold following elective orthopedic surgery and remained elevated up to 5 days. To examine the mechanism(s) of increased Vn synthesis, hepatic Vn mRNA expression and serum levels were examined in three rat models of acute inflammation: LPS (i.v.), CFA (i.p.), or turpentine (s.c.) injection. The serum concentration of Vn increased approximately twofold 24 h following treatment with turpentine. The expression of Vn mRNA in the liver increased markedly as early as 3 h after treatment in these models and remained elevated up to 18 h. Northern blot analysis of RNA isolated from fractionated liver cells derived from rats treated with LPS indicated that Vn was mainly expressed in hepatocytes, but not in the endothelial or nonparenchymal cell fractions. To analyze the individual effects of raised corticosterone and IL-6 levels on the expression of hepatic Vn mRNA, rats were injected (i.p.) with either dexamethasone or purified recombinant rat IL-6. Vn mRNA expression was elevated within 1 h after IL-6 injection, whereas dexamethasone-injected rats showed unchanged Vn expression. Vn mRNA also was increased in rats chronically injected with IL-6. These results indicate that the Vn gene is up-regulated in acute and chronic inflammation, and this induction is primarily mediated by IL-6.

Animals↗
PubMed1995

The effects of low molecular weight and standard heparin on calcium loss from fetal rat calvaria.

Osteoporosis is a well-recognized complication of long-term heparin use. However, the mechanisms by which heparin can influence bone metabolism are unclear. We report here that unfractionated heparin stimulates the process of bone resorption and that the low molecular weight heparins (LMWHs), enoxaparin, fragmin, logiparin, and ardeparin produce significantly less calcium loss than unfractionated heparin. To assess calcium loss from bone, we quantified the release of 45Ca into the culture medium of fetal rat calvaria. 45Ca release was increased in a dose-dependent manner by the addition of either unfractionated heparin or the LMWHs; but more than 50-fold higher LMWH concentrations were required to obtain an equivalent effect to unfractionated heparin. Thus, at concentration > or = 2 micrograms/mL (0.35 anti-Xa units/mL), unfractionated heparin stimulated 45Ca release 1.53 +/- 0.06 fold. 45Ca release was increased to a similar extent by the addition of either 10(-7) mol/L parathyroid hormone (PTH) or 10(-6) mol/L 1,25 dihydroxyvitamin D3 (1,25 Vit D3). In contrast to unfractionated heparin, LMWH concentrations > or = 100 micrograms/mL (> or = 14.0 anti-Xa units/mL) were required before maximum isotope release was observed. At concentrations well above therapeutic levels, the LMWHs stimulated 45Ca release by only 1.25 /+- 0.01-fold. Heparins with high and low antithrombin III affinities stimulated 45Ca release equally well. Both size and sulfation were found to be major determinants of heparin's ability to promote isotope release. Thus, the ability of defined heparin fragments to stimulate 45Ca release correlated with their molecular weight, and after N-desulfation the ability of heparin to induce isotope release was greatly diminished. Dermatan sulfate had no effect on 45Ca release. We conclude that size and sulfation are major determinants of heparin's ability to promote bone resorption and that the risk of heparin-induced osteoporosis may be reduced by the use of LMWH preparations.

Animals↗
PubMed1995

Pseudodeficiency of arylsulphatase A: strategy for clarification of genotype in families of subjects with low ASA activity and neurological symptoms.

A benign deficiency (pseudodeficiency) of the lysosomal enzyme arylsulphatase A (ASA) (EC 3.1.6.8) towards synthetic substrates complicates the diagnosis of metachromatic leukodystrophy (MLD). The pseudodeficiency is due to a single base substitution in the 3'-untranslated region of the ASA gene (1524+95 A-->G) and it has been reported that this mutation (PD2) always occurs on a chromosome carrying a second mutation in the ASA gene (PD1), which abolishes an N-glycosylation site (N350S). Analysis of the two PD mutations in the ASA gene separately was carried out in a large group of subjects with neurological symptoms and low ASA activity, including close relatives and MLD patients. The relationship between ASA enzyme activity and the different genotypes identified is presented. Evidence for the existence of an allele containing the PD2 mutation alone is presented. A strategy for cases with low ASA activity and neurological symptoms in families carrying a PD allele or both PD and MLD alleles is proposed.

Cerebroside-Sulfatase↗