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Biomedical subjects

M Horton

Publications and source records attributed to M Horton.

At least 37 records · Page 2Linked to original sources
PubMed1996

Breast cancer in Nebraska: recent trends in incidence, mortality, and screening.

Data from the Nebraska Cancer Registry indicate that the State's female breast cancer incidence rate did not increase or decrease significantly during the period 1987-1993, although the percentage of in situ diagnoses increased from 8% to 13%. Similarly, breast cancer mortality among Nebraska women has remained relatively constant during the past decade (1985-1994). According to Nebraska's Behavioral Risk Factor Survey, screening mammography rates among Nebraska women have shown striking increases in recent years: in 1994, nearly half (48%) of all women 50 and older reported that they had had a mammogram within the past year, up from 24% in 1988. Nebraska's breast cancer incidence, mortality, and screening rates remain lower than U.S. rates.

Adult↗
PubMed1995

Hepatic cryotherapy: double-freeze cycles achieve greater hepatocellular injury in man.

Hepatic cryotherapy is a relatively new technique used to treat both primary and secondary tumors. This paper concerns the changes in serum aspartate transaminase (AST) in 45 patients following both single and double freeze with partial thaw cycles. There was considerable elevation in serum AST, greatest on the day of operation, and there was a significantly higher peak AST following the double-freeze cycles (1159; SE, 117.5) compared with single-freeze/thaw procedures (437; SE, 61.7). This finding indicates greater hepatocellular disruption which may be important both in planning clinical hepatic cryosurgery to achieve adequate destruction and also to avoid the morbidity of the cryoshock phenomenon.

Aspartate Aminotransferases↗
PubMed1995

Influence of age, renal and liver impairment on the pharmacokinetics of risperidone in man.

The pharmacokinetics of the antipsychotic agent risperidone were investigated in healthy young and elderly subjects, cirrhotic patients and patients with moderate and severe renal insufficiency. In a comparative trial, a single oral 1-mg dose was administered to fasting subjects. Plasma and urine concentrations of the parent compound risperidone and the active moiety (i.e. risperidone plus 9-hydroxy-risperidone) were measured by radioimmunoassays. No or only small changes in plasma protein binding were observed in hepatic and renal disease, whereas the protein binding was not influenced by aging. The inter-individual variability in plasma concentrations of the active moiety was much less than the variability in plasma concentrations of risperidone. Three out of six subjects, behaving like poor metabolizers, were on medication (thiethylperazine, amitriptyline, metoprolol) that may inhibit risperidone metabolism by CYP2D6 (debrisoquine 4-hydroxylase). The pharmacokinetics of risperidone in elderly and cirrhotic patients were comparable to those in young subjects, whereas total oral clearance was reduced in renal disease patients. The elimination rate and clearance of 9-hydroxy-risperidone was reduced in elderly and renal disease patients because of a diminished creatinine clearance. The CL(oral) of the active moiety, which is primarily 9-hydroxy-risperidone, was reduced by about 30% in the elderly and by about 50% in renal disease patients. In addition, the t1/2 of the active moiety was prolonged (19 h in young subjects versus about 25 h in elderly and renal disease patients). Based upon the pharmacokinetics of the active moiety, a dose reduction and a cautious dose titration is advised in the elderly and in patients with renal disease. In cirrhotic patients, the single-dose pharmacokinetics were comparable to those in healthy young subjects.

Adult↗
PubMed1995

Cryotherapy of liver tumours--a practical guide.

The use of cryotherapy for the treatment of some unresectable liver tumours has been clearly established as a therapeutic option. Intra-operative ultrasound has enhanced the process by enabling the surgeon to identify hepatic lesions and to allow visualisation of the freezing process to ensure that the cryolesion will include the tumour mass. The purpose of this paper is to provide a practical guide to surgeons who wish to perform cryotherapy of liver tumours. Patient selection and anaesthetic considerations are important. The surgeon should be able to deal with the complications of cryotherapy, particularly the intra-operative haemorrhage which may arise from cracking of the hepatic parenchyma as the iceball thaws. Follow-up is based on tumour marker assay and imaging of the liver and repeat cryotherapy can be considered for selected cases.

Cryosurgery↗
PubMed1994

Evaluation of relative fertility of cryopreserved goat sperm.

This study was designed to compare differences in the in vivo fertility of cryopreserved goat semen assessed by heterospermic insemination with differences in in vitro analyses. Five groups of does were inseminated with mixed frozen-thawed semen from different pairs of bucks. The percentage of offspring sired by each buck in the pair was compared with the relative ability of spermatozoa from that frozen-thawed ejaculate to penetrate zona-free hamster ova, relative post-thaw acrosomal integrity, ability to undergo an acrosome reaction during in vitro capacitation, and assessments of sperm motility. In 4 of the 5 different insemination pairs, the ratio of offspring born was other than 1:1. Acrosomal integrity, ability of spermatozoa to undergo an acrosome reaction, and parameters of sperm motility were not correlated with differences in relative fertility in this experiment using ejaculates from fertile bucks. The ability of spermatozoa to fuse with the oocyte plasma membrane was highly correlated with relative in vivo fertility (R2=0.78, P=0.04). This suggests that fusion with the oocyte plasma membrane is an event in the fertilization process in which significant variation exists among fertile bucks. Assessment of ability of spermatozoa to fuse with zona-free hamster ova may contribute to analysis of post-thaw fertility of frozen-thawed buck semen.

Journal Article↗
PubMed1993

Biochemical characterization of human osteoclast integrins. Osteoclasts express alpha v beta 3, alpha 2 beta 1, and alpha v beta 1 integrins.

The study of osteoclast integrins has been previously hampered by the lack of a source of large numbers of purified osteoclasts. Osteoclastoma, a human giant cell tumor of bone, supplied a rich source of osteoclasts within a tissue containing many diverse cell types. Osteoclastoma integrin immunostaining confirmed the presence of the integrin alpha v beta 3 complex and the alpha 2 and beta 1 integrin subunits on osteoclasts. However, weak integrin expression, for example with alpha v beta 5, was difficult to interpret. Purification with magnetic beads coated with vitronectin receptor monoclonal antibody (13C2) enabled osteoclast membranes to be isolated with high purity and yield (57%) from osteoclastoma tissue. Positively (osteoclast-enriched) selected membranes were biochemically assessed for integrin expression by immunoprecipitation and visualization by non-radioactive enhanced chemiluminescence. alpha 1, alpha 4, alpha 6, alpha 8, alpha M, alpha X, gpIIb, beta 4, beta 6, and beta 8 integrin chains were undetectable at a sensitivity of 1 ng. alpha 3, alpha 5, alpha L, beta 2, and alpha v beta 5 were found in the negatively selected osteoclastoma tissue but not in the positively purified osteoclast membranes. The presence of alpha v beta 1 and alpha 2 beta 1 dimers was demonstrated biochemically on the immunoisolated osteoclast membranes. Osteoclast alpha v beta 3 isolation by Arg-Gly-Asp (RGD) affinity chromatography for NH2-terminal amino acid sequencing confirmed that the osteoclast vitronectin receptor was identical to that previously characterized on other cell types. In situ hybridization using human alpha v riboprobes in osteoclasts from human and rodent bone further demonstrated the high level and specificity of expression of alpha v vitronectin receptor in osteoclasts.

Amino Acid Sequence↗
PubMed1993

Blocking monoclonal antibodies to alpha V beta 3 integrin: a unique epitope of alpha V beta 3 integrin is present on human osteoclasts.

Integrins are a family of cell surface glycoproteins that promote cell adhesion. The integrin alpha V beta 3, vitronectin receptor, is a major integrin expressed by osteoclasts. To further investigate the role of alpha V beta 3 in cell adhesion, we generated and characterized monoclonal antibodies to alpha V beta 3 by immunizing BALB/c mice with purified alpha V beta 3 protein. Three monoclonal antibodies (mAbs), 9D4.9.1, 9G2.1.3, and 10C4.1.3, from a total of more than 1100 positive cultures which bound alpha V beta 3, were characterized extensively: mAbs 9G2.1.3 and 10C4.1.3 recognize the alpha V beta 3 complex whereas mAb 9D4.9.1 reacts with the beta 3-chain shared between the alpha V beta 3 complex and gpIIbIIIa. Further epitope mapping using flow microfluorometry analysis and histochemical staining of various tissues showed that 9D4.9.1 and 10C4.1.3 recognized distinct epitopes. Ligand-binding studies using cell-bound and purified alpha V beta 3 demonstrated that all three mAbs blocked fibrinogen binding. Vitronectin binding was blocked by mAb 9D4.9.1 and, less effectively, by mAb 10C4.1.3; mAb 9G2.1.3 was without effect. All three mAbs recognized osteoclasts from human tissues; mAb 9G2.1.3 also stained osteoclasts from a wide range of nonhuman species. Monoclonal antibodies 9D4.9.1 and 9G2.1.3 bound to a panel of cultured cell lines and various tissues. In contrast, mAb 10C4.1.3 bound only weakly or not at all to tissues expressing alpha V beta 3 with the exception of osteoclasts. Thus, mAb 10C4.1.3 showed a very narrow tissue specificity being restricted to high-level expression on human osteoclasts.

Amino Acid Sequence↗
PubMed1993

Current tobacco use policies in Nebraska public schools.

A critical effort to reduce the harmful effects of tobacco is to promote tobacco abstinence among the nation's adolescent population. In this regard, the message of tobacco tolerance within the education system of the State of Nebraska was examined. Although the majority of schools surveyed have an encouraging policy regarding student smoking, it has not yet been universally implemented. In addition, the tobacco-use policies for non-students within public school buildings is concerning. The Nebraska Indoor Clean Air Act and the recent Environmental Protection Agency warning on second-hand smoke provides a framework for change. Health care providers can be proactive in encouraging their school districts to promote the goal of a Tobacco-Free Nebraska.

Adolescent↗
PubMed1991

Enrichment of a second class of native acceptor sites for the avian oviduct progesterone receptor as intact chromatin fragments.

Several classes of specific progesterone receptor (PR) nuclear binding sites (acceptor sites) have previously been identified in avian oviduct chromatin on the basis of different binding affinities. Recently, two classes of acceptor proteins (AP) that are associated with these binding sites in the avian oviduct have been identified. These APs were termed receptor binding factors (RBF-1 and -2), and one (RBF-1) has been purified [Schuchard et al. (1991) Biochemistry 30, 4535-4542]. The RBF-1 is associated with the highest affinity class of sites in the intact chromatin, and the RBF-2 is associated with the second highest affinity class of sites. The PR binding sites and their associated RBF-2 protein remain with the residual chromatin fraction following extraction by 4 M Gdn-HCl. This Gdn-HCl-treated chromatin has been termed nucleoacidic protein (NAP). This paper describes the 200-fold enrichment of the native RBF-2 class of PR acceptor sites beginning with the DNase I digestion of NAP to obtain DNase-resistant fragment (NAPf) containing approximately 150 bp of DNA. The PR binding sites are further enriched by high-performance or fast protein liquid chromatography and chromatofocusing. Anti-RBF-1/RBF-2 protein antibodies identify antigens that coelute with the PR binding activity. Hybridization analysis of the DNAf from the enriched NAPf demonstrates sequence homologies with the nuclear matrix DNA as well as with genomic sequences of the rapid steroid responding nuclear protooncogenes c-myc and c-jun. However, comparative analyses of the whole genomic DNA with the nuclear matrix DNA indicate that the RBF-2 (NAPf) is largely nonnuclear matrix.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Piroxicam-beta-cyclodextrin: effects on gastrointestinal blood loss and gastric mucosal appearance in healthy men.

Thirty-six healthy men aged 20-31 years took part in a randomized, double-blind, double-dummy, parallel-group study to compare the effects of repeated doses of piroxicam-beta-cyclodextrin, piroxicam and placebo on faecal blood loss and the endoscopic appearances of gastric and duodenal mucosa. After an initial endoscopy, subjects received on day 0 autologous erythrocytes labelled with 51Cr. Complete daily faecal collections were then made from days 6 to 12. From days 13 to 40, subjects received daily by mouth either piroxicam-beta-cyclodextrin (containing 20 mg piroxicam), piroxicam 20 mg, or placebo. Complete faecal collections were made daily from days 13 to 41; blood samples for red-cell 51Cr activity were taken weekly. Endoscopy was repeated 16-20 h after the last dose of medication. Faecal blood loss was calculated from 51Cr activity of blood and faeces. Compliance with medication was confirmed by blood sampling on days 20, 27 and 34. General tolerability of the medication was good, although 1 subject was withdrawn from piroxicam-beta-cyclodextrin and 1 from piroxicam treatment because of abdominal pain. There were no clinically significant changes in haematology, biochemistry or urinalysis results in any subject. Endoscopic appearances deteriorated moderately in 3 subjects receiving piroxicam and 3 receiving piroxicam-beta-cyclodextrin, but did not deteriorate in any subject receiving placebo. There was a trend for cumulative blood loss to be higher for piroxicam than for the other treatments in the last 12 days of dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

High dose cytosine arabinoside in the initial treatment of adults with acute lymphoblastic leukaemia.

In a study conducted at St Bartholomew's Hospital between 1972 and 1982, using moderately intensive therapy (OPAL/HEAV'D), a low blast count at presentation (less than 10 x 10(9) 1(-1)) and common ALL (C-ALL) phenotype correlated favourably with duration of remission. Fifty-four patients (age range 15-57, median 32) subsequently received a modification of the previous treatment programme which included high-dose ara-C 2 g m-2 b.d. for 6 days as cycle 3 (OPAL + HD ARA-C). CR was achieved in 36/54 (67%) patients, response correlating favourably with younger age (15-30 years vs 31-57 years, P = 0.02). Three patients died in CR. Overall, there was no difference in survival or remission duration between patients who received high dose ara-C and those in the control group. However, in contrast to the early results, there was a reversal in the relevance of the prognostic factors with a trend in favour of high blast count (greater than 10 x 10(9) 1(-1)) and T-cell phenotype in terms of remission duration. Moreover, comparison of duration of remission for the previously defined prognostic groups according to therapy suggests that the prognosis of patients with 'high risk' disease (T, B, null ALL or high blast count) is improved with more intensive therapy. In contrast, those with 'low risk' disease (C-ALL and low blast count) have a better prognosis with less intensive therapy. These observations confirm those of others and allow for individualization of therapy on the basis of pre-treatment variables.

Adolescent↗
PubMed1990

Lornoxicam, indomethacin and placebo: comparison of effects on faecal blood loss and upper gastrointestinal endoscopic appearances in healthy men.

Forty-five healthy men aged 21-34 years took part in a double-blind, parallel-group, placebo-controlled study of the effects of 28 days' treatment with lornoxicam 4 mg twice daily or indomethacin 50 mg twice daily on faecal blood loss and the endoscopic appearances of gastric and duodenal mucosa. After an initial endoscopic examination, subjects received, intravenously, on day 0, autologous erythrocytes labelled with 51Cr. Complete daily faecal collections were then made from days 6-12, 20-26 and 34-40. The drug treatments or placebo were given from days 13-41. Faecal blood loss was calculated from 51Cr-specific activity of blood and faeces. Endoscopy was repeated 4-8 hours after the last dose of medication; mucosal appearance was graded on a 5-point scale. Lornoxicam caused no more adverse events than placebo; indomethacin caused more indigestion and central nervous system effects, and one subject in this group was withdrawn from the study. Median total blood losses during the pre-treatment and the second and fourth weeks of treatment were respectively 3.33, 3.95 and 5.71 ml for lornoxicam, 2.87, 7.04 and 7.75 ml for indomethacin, and 4.55, 3.64 and 4.13 ml for placebo. Differences between treatments were not statistically significant (P = 0.081 for second week of treatment, P = 0.383 for fourth week of treatment; Kruskal-Wallis test). The effect of chlortenoxicam on faecal blood loss in this study was thus intermediate between placebo and indomethacin, but within- and between-subject variability was such that the differences were not statistically significant. Endoscopic findings were normal in most subjects before and after all treatments, but indomethacin was associated with a slightly greater deterioration in endoscopic score and was the only treatment associated with Grade 3 appearance (in a single patient) in post-treatment endoscopy.

Adult↗