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Biomedical subjects

M Stroud

Publications and source records attributed to M Stroud.

At least 19 recordsLinked to original sources
PubMed2006

Impact of oedema on recovery after major abdominal surgery and potential value of multifrequency bioimpedance measurements.

BACKGROUND: The consequences of generalized oedema following major abdominal surgery are under-recognized, and its causes are poorly understood. METHODS: Thirty-eight patients (21 men and 17 women) were observed for the occurrence of oedema after major abdominal surgery. Oedema formation was related to fluid balance, changes in whole-body bioimpedance (Z) measured at four frequencies (5, 50, 100 and 200 kHz), and clinical outcome. RESULTS: The 20 patients who developed oedema were older than those who did not (mean(s.d.) 73(9) versus 63(14) years; P = 0.007). Fluid intake over the first 5 days after surgery was similar in both groups, but those with oedema excreted less total fluid (16.9(2.4) versus 19.7(3.5) litres; P = 0.022). Oedema was associated with a delay in tolerating solid food (P = 0.001) and opening bowels (P = 0.020), a prolonged hospital stay (median 17 (range 8-59) versus 9 (range 4-27) days; P = 0.001) and more postoperative complications (13 of 20 versus four of 18 patients; P = 0.011). The preoperative ratio of whole-body impedance at 200 kHz to that at 5 kHz was higher in those who subsequently developed oedema (0.81(0.03) versus 0.78(0.02); P = 0.015). CONCLUSION: The development of oedema after major abdominal surgery is associated with increased morbidity. Age and reduced ability to excrete administered fluid load are significant aetiological factors and bioimpedance analysis can potentially identify patients at risk.

Abdomen↗
PubMed2004

Early hormonal therapy stabilizes hemodynamics during donor procurement.

BACKGROUND: Hemodynamic instability has been implicated in the loss of otherwise transplantable organs. We examined the hypothesis that administration of hormonal therapy early during donor management would stabilize hemodynamics and increase the number of organs procured. METHODS: We retrospectively analyzed 133 consecutive donor records from a single organ procurement organization. Controls (C) received no early hormonal therapy. A steroid group (S) received methylprednisolone only and a combination hormonal therapy group (CH) received thyroxine, methylprednisolone, dextrose, and insulin at the start of donor management (t(0h)). Adrenergic support was adjusted to maintain mean arterial blood pressure (MAP) at > or =60 mm Hg. Doses of adrenergic agents were assessed at t(0h), 4 hours (t(4h)), and just prior to procurement (t(proc)). RESULTS: Baseline characteristics were similar in all groups. Dosages of adrenergic agents decreased over time in all groups. A significant decrease in adrenergic requirements was seen in the CH group compared with the C group at t(4h) and t(proc). A trend toward decreased adrenergic requirements was noted in S compared with C at t(4h) and t(proc). Slightly more total organs were procured from S and CH compared with C. CONCLUSIONS: Significantly less adrenergic support was required with early use of CH. A similar (although nonsignificant) reduction was seen with S. The benefit(s) of CH vs corticosteroids alone remains uncertain and requires further study.

Hemodynamics↗
PubMed2001

Methods for the stable isotopic analysis of chlorine in chlorate and perchlorate compounds.

Chlorate and perchlorate compounds, used as herbicides, solid fuel propellants, and explosives, are increasingly recognized as pollutants in groundwater. Stable isotope characterization would permit both environmental monitoring of extent of remediation and forensic characterization. Stoichiometric reduction to chloride (greater than 98% yield), by Fe(II) for chlorate and alkaline fusion-decomposition for perchlorate, allows analysis by standard methods to give highly reproducible and accurate delta37Cl results (0.05/1000, 2 x standard error). Analysis of various compounds from different suppliers yielded delta37Cl values for chlorate samples near to +0.2/1000 (SMOC), but one has within-sample heterogeneity of 0.5/1000, possibly due to crystallization processes during manufacture. Results for perchlorate samples also are generally near +0.2/1000, but one is +2.3/1000 (SMOC). The initial results suggest that both forensic and environmental applications might be feasible.

Chlorates↗
PubMed2001

Comparison of calcaneal ultrasound and DXA to assess the risk of corticosteroid-induced osteoporosis: a cross-sectional study.

Patients on long-term oral corticosteroids have an increased risk of low bone mass and fragility fractures. Fracture risk rises soon after commencement of corticosteroid therapy and it is possible that these agents adversely influence bone architecture disproportionately to their effect on bone mass. The best means of assessing bone status in patients using corticosteroids remains uncertain, but quantitative ultrasound of the calcaneus may provide evidence of microarchitectural changes not detected by dual-energy X-ray absorptiometry (DXA). Patients with Crohn's disease have an increased risk of low bone mineral density (BMD), the etiology of which is multifactorial but includes corticosteroid use. We studied 118 consecutive patients with Crohn's disease, 21 of whom used continuous oral corticosteroids, 70 of whom were intermittent users, and 27 who had never used the drug. All patients received DXA of the lumbar spine, hip and calcaneus and quantitative ultrasound (QUS) of the calcaneus. The different techniques were compared using a femoral neck T-score < or = -1.5 as the threshold of corticosteroid-induced osteoporosis. When compared with the femoral neck T-score, there were no significant differences between the predictive values of lumbar spine DXA, calcaneal DXA or calcaneal QUS to identify low femoral neck BMD. However, the absolute T-score required to give similar discriminatory capacity to femoral neck T-score varied substantially (T= -0.81 to -1.5) between the different measurement techniques and sites.

Absorptiometry, Photon↗
PubMed2000

Cloning and expression of the histo-blood group Pk UDP-galactose: Ga1beta-4G1cbeta1-cer alpha1, 4-galactosyltransferase. Molecular genetic basis of the p phenotype.

The molecular genetic basis of the P histo-blood group system has eluded characterization despite extensive studies of the biosynthesis of the P(1), P, and P(k) glycolipids. The main controversy has been whether a single or two distinct UDP-Gal:Galbeta1-R 4-alpha-galactosyltransferases catalyze the syntheses of the structurally related P(1) and P(k) antigens. The P(1) polymorphism is linked to 22q11.3-ter. Data base searches with the coding region of an alpha4GlcNAc-transferase identified a novel homologous gene at 22q13.2 designated alpha4Gal-T1. Expression of full coding constructs of alpha4Gal-T1 in insect cells revealed it encoded P(k) but not P(1) synthase activity. Northern analysis showed expression of the transcript correlating with P(k) synthase activity and antigen expression in human B cell lines. Transfection of P(k)-negative Namalwa cells with alpha4Gal-T1 resulted in strong P(k) expression. A single homozygous missense mutation, M183K, was found in six Swedish individuals of the rare p phenotype, confirming that alpha4Gal-T1 represented the P(k) gene. Sequence analysis of the coding region of alpha4Gal-T1 in P(1)+/- individuals did not reveal polymorphisms correlating with P(1)P(2) typing.

Amino Acid Sequence↗
PubMed1993

Long-term maintenance of weight loss following supplemented fasting.

One hundred two obese subjects were evaluated 2-3 years following treatment in a combined behavior therapy and very low calorie diet (VLCD) program. Average weight loss after VLCD was 27.2 kg; average weight loss at follow-up was 11.3 kg. Subjects who reported high levels of exercise were more successful in maintaining weight loss (17.5 kg at follow-up) than were those who exercised only moderately (9.3 kg), or not at all (5.6 kg). Enrolling in a weight loss maintenance program also minimized weight regain. Subjects who participated in maintenance for more than 8 months sustained more average weight loss at follow-up (19.1 kg) than did subjects who participated for 8 months or less (10.6 kg), or subjects who did not participate in maintenance (6.6 kg).

Adult↗
PubMed1993

Dual analyte immunoassay in neural tube defect and Down's syndrome screening: results of a multicentre clinical trial.

We report a multicentre clinical field trial of a novel dual analyte enzyme immunoassay method for the simultaneous measurement of alpha-fetoprotein (AFP) and free beta-human choriogonadotropin (hCG) in the same microtitre well. The assay was shown to have good technical performance in the hands of all trial centres, with between assay coefficients of variation better than 10% for both analyte across the whole of the assay ranges. The method compared well with single analyte measuring procedures and produced acceptable performance as judged by external quality assurance criteria. Recovery of added analyte and analyte dilution curves also showed acceptable performance. In clinical evaluation of a large set of neural tube defect cases, good clinical discrimination from unaffected cases was observed using AFP. With over 150 Down's syndrome cases, the combination of AFP and free beta hCG confirmed the high detection rates achievable using this marker combination, with detection rates in excess of 70% in early gestation. We conclude that the combination of clinically superior markers coupled with technologically innovative assay design will lead to more efficient Down's screening programmes.

Adolescent↗
PubMed1991

A specific type of ganglioside as a modulator of insulin-dependent cell growth and insulin receptor tyrosine kinase activity. Possible association of ganglioside-induced inhibition of insulin receptor function and monocytic differentiation induction in HL-60 cells.

Insulin-dependent cell growth has been correlated with insulin receptor function, particularly receptor-associated kinase activity, in in vitro studies. The insulin-dependent phosphorylation of the 95-kDa receptor subunit was clearly inhibited, in a concentration-dependent manner, by the presence of unbranched neolacto series gangliosides having a NeuAc2----3Gal terminus, particularly 2----3-sialosylparagloboside (2----3SPG; IV3NeuAc-nLc4), but not by other gangliosides with a NeuAc2----6Gal terminus or by branched neolacto series gangliosides (e.g. G10). Such inhibition of phosphorylation was minimal with ganglio series gangliosides and negligible with sphingosine, neutral glycolipids, or sulfatide. 2----3SPG did not affect insulin binding to the insulin receptor. Insulin-dependent cell growth and its inhibition by 2----3SPG were observed in three human cell lines so far tested: lymphoid cell line IM9, promyelocytic leukemia cell line HL-60, and erythroleukemia cell line K562. Since IM9 cells contain a much higher quantity of insulin receptor than do HL-60 or K562 cells, insulin-dependent receptor phosphorylation and its inhibition by 2----3SPG in intact cells were clearly observed with IM9 cells. Receptor phosphorylation in intact cells was inhibited when cells were preincubated in the presence of 2----3SPG. Insulin-dependent growth of HL-60 and K562 cells was also inhibited by prolonged culture (96-144 h) with exogenous 2----3SPG. Subsequent to the inhibition of insulin-dependent HL-60 cell growth, a remarkable phenotypic transformation was observed, i.e. changes in morphology, enzymes, and cell-surface markers to those characteristic of monocytes. The level of 2----3SPG in HL-60 cells increased when cells were cultured with 1 alpha,25-dihydroxyvitamin D3 to the same degree seen in cells cultured with 5 microM 2----3SPG. Both these treatments led to inhibition of insulin-dependent cell growth, followed by induction of monocytic differentiation. Thus, the cellular level of 2----3SPG may modulate insulin-dependent cell growth and define the lineage specificity of differentiation through modulation of receptor-associated kinase activity.

Antigens, Differentiation, Myelomonocytic↗
PubMed1990

Isolation to homogeneity and partial characterization of a histo-blood group A defined Fuc alpha 1----2Gal alpha 1----3-N-acetylgalactosaminyltransferase from human lung tissue.

The soluble histo-blood group A glycosyltransferase (Fuc alpha 1----Gal alpha 1----3-N-acetylgalactosaminyltransferase) was purified approximately 600,000-fold to homogeneity from human lung tissue. The enzyme was solubilized in 1% Triton X-100, partially purified by affinity chromatography on Sepharose 4B, and eluted with UDP. Final purification was obtained by twice repeated fast protein liquid chromatography ion exchange (Mono STM) with NaCl gradient elution and reverse-phase chromatography (proRPC) with acetonitrile gradient elution. Identity of the purified protein was established by (i) demonstration of the putative A transferase protein only in affinity-purified extracts of A but not O individuals, and (ii) specific immunoprecipitation of enzyme activity and putative protein with monoclonal antibodies. Sodium dodecyl sulfate electrophoresis revealed a single protein band with apparent Mr of approximately 40,000 under both reducing and nonreducing conditions. Digestion with N-glycanase yielded a reduction in Mr of approximately 6,000 (estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis), suggesting that the A transferase is a glycoprotein with N-linked carbohydrate chains. Amino acid composition and N-terminal amino acid sequence of the intact transferase, as well as of peptides released by endolysyl peptidase digest or cyanogen bromide cleavage, are presented.

ABO Blood-Group System↗
PubMed1990

Cellular and humoral mediators of sepsis syndrome.

The story of mediators in sepsis syndrome is developing extremely rapidly and continues to unfold. This discussion has focused on those areas most studied and those that have the greatest clinical implications in the context of current knowledge. There are a number of mediators under active investigation that have not been reviewed here because their discussion is beyond the scope of this article. Just how all the pieces of the intricate cascade of events ultimately fit together is yet to be seen. However, the availability of important probes, such as cyclooxygenase inhibitors, TNF, anti-TNF, IL1, anti-IL1, anti-proteases, antioxidants, and antiendotoxin, is allowing major progress to be made in a short period of time. Transferring this knowledge to the bedside and everyday clinical practice is a slower process, but the prospects are bright for innovative new therapies for sepsis syndrome, septic shock, and the multiple organ failure associated with these clinical entities.

Antibody Formation↗
PubMed1990

Surgical management of Wolff-Parkinson-White syndrome in infants and small children.

Surgical ablation of accessory conduction pathways has rarely been reported in infants and small children with Wolff-Parkinson-White syndrome. In the interval January 1985 to September 1988, 19 infants and children aged 5 or younger have undergone surgical ablation of accessory conduction pathways because of recurrent supraventricular tachycardia. There were 12 (63%) boys and seven (37%) girls. Age ranged from 4 to 66 months (mean 33.8 months). Nine infants were less than 24 months old. Weight ranged from 5.5 to 2.16 kg (mean 13.2 kg). All 19 patients had symptoms, with duration of symptoms ranging from 3 to 63 months (mean 21 months). Accessory conduction pathways were classified preoperatively as left free wall in four (21%), right free wall in nine (47%), and posterior septal in six (32%). No multiple pathways were recognized preoperatively. Left ventricular function was abnormal in four (21%) preoperatively. Free wall pathways (n = 13) were surgically dissected and septal pathways (n = 6) were cryoablated at -70 degrees C. Mean cardiopulmonary bypass time was 60 +/- 4 minutes. Mean crossclamp time was 42 +/- 2 minutes in those undergoing surgical dissection. Mean postoperative stay was 6.4 +/- 0.2 days. There were no deaths, no significant postoperative complications, and no instance of complete heart block. All patients were considered cured at the time of discharge. At a mean follow-up of 12.7 months, 18 (94.7%) remain cured. One patient with Ebstein's anomaly and a right free wall pathway had a recurrent supraventricular tachycardia 3 months postoperatively, and repeat electrophysiologic study has shown a previously unsuspected anterior septal pathway. Ventricular function returned to normal in all four patients who had abnormal function preoperatively. Surgical ablation of accessory conduction pathways can be safely done in infants and small children with results equal to those obtained in adults.

Adolescent↗
PubMed1989

Specific interaction between Lex and Lex determinants. A possible basis for cell recognition in preimplantation embryos and in embryonal carcinoma cells.

The Lex determinant (Gal beta 1----4[Fuc alpha 1----3]GlcNAc-beta 1----R) has been implicated as having a role in mediating compaction of the mouse embryo at the morula stage (Fenderson, B., Zehavi, U., and Hakomori, S. (1984) J. Exp. Med. 160, 1591-1596). Here, we present evidence suggesting a role for Lex in F9 embryonal carcinoma cell adhesion and a mechanism for Lex recognition based on carbohydrate-carbohydrate interaction. Homotypic aggregation of F9 cells was inhibited by lacto-N-fucopentaose III, and F9 cells showed a preferential interaction with Lex liposomes. The following observations suggest that the structure capable of recognizing Lex per se on F9 cells is Lex: (i) Cell surface-labeled components solubilized in octylglucoside, affinity-bound on an Lex-octyl-Sepharose column, contained glycoproteins reactive with anti-Lex antibody. (ii) Liposomes containing Lex showed significant interaction with Lex glycolipid, but not other glycolipids, coated on a plastic surface. (iii) Liposomes containing Lex glycolipid were found to self-aggregate, whereas liposomes containing paragloboside (nLc4) or sialylparagloboside (IV3NeuAcnLc4) did not. (iv) The diffusibility of 3H-labeled lacto-N-fucopentaitol III (but not I or II), incubated with Lex liposome, from the lower to the upper Boyden chamber through a semipermeable membrane was inhibited. In all these experiments (i-iv), the interaction of Lex to Lex (or Lex to lacto-N-fucopentaose III) was clearly observed only in the presence of Ca2+ and Mg2+ and was enhanced by the presence of Mn2+. These interactions were inhibited by EDTA. The results suggest the novel hypothesis that carbohydrate-carbohydrate interactions may play an important role in controlling cell recognition during F9 cell aggregation and during embryonic development.

Animals↗
PubMed1988

Monoclonal antibodies directed to the blood group A associated structure, galactosyl-A: specificity and relation to the Thomsen-Friedenreich antigen.

Two monoclonal antibodies, HH8 and HH9, have been established after immunization of mice with galactosyl-A glycolipid antigen having the terminal structure, Gal beta 1----3GalNAc alpha 1----3[Fuc alpha 1----2]Gal beta 1----R, which is the precursor for type 3 chain A (repetitive A) and type 3 chain H (A-associated H). Both antibodies react strongly and specifically with galactosyl-A, but HH8 (IgM) showed strong hemagglutination of blood group A1, A2, O and B erythrocytes after sialidase treatment, while HH9 (IgG1) did not react with human erythrocytes even after sialidase treatment. HH8 and anti-T antibody, but not HH9, reacted with glycophorin A after sialidase treatment. The reactivity of HH8 with glycophorin A was abolished by beta-galactosidase and was inhibited by liposomes containing galactosyl-A, but not other glycolipids. In addition, anti-T antibody and peanut lectin reacted specifically with galactosyl-A glycolipids. These findings indicate that HH8 recognizes the terminal disaccharide Gal beta 1----3GalNAc alpha 1----R, which is the same sequence as the classically known Thomsen-Friedenreich antigen (T-antigen), whereas HH9 does not cross-react with T-antigen but recognizes the entire galactosyl-A structure. The T-antigen was also demonstrated by immunohistology with HH8 after neuraminidase treatment in a subset of cells in stratified epithelium.

ABO Blood-Group System↗
PubMed1987

Isolation and characterization of novel glycolipids with blood group A-related structures: galactosyl-A and sialosylgalactosyl-A.

Two glycosphingolipids with the following novel structures have been isolated from human blood cells and characterized by NMR, direct probe mass spectrometry, fast atom bombardment-mass spectrometry, and methylation analysis: (Formula: see text). Both structure i and structure ii are characterized by substitution of beta-galactosyl or sialosyl-beta-galactosyl residue at the terminal alpha-GalNAc residue of blood group A determinant and are therefore specific products associated with the blood group A phenotype.

ABO Blood-Group System↗