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Biomedical subjects

R Duncan

Publications and source records attributed to R Duncan.

At least 163 records · Page 9Linked to original sources
PubMed1990

General practice computing in Scotland.

OBJECTIVE: To investigate a method of assessing the extent of routine patient data held on computer by Scottish general practitioners. DESIGN: An "electronic questionnaire" in the form of an interrogation questionnaire was used to extract a subset of data from practice computers running a standard software package (the general practice administrative system for Scotland, GPASS). The data were retained by each practice and also collected and analysed centrally to produce regional and national data. SUBJECTS: All 257 general practices in Scotland using GPASS software were sent the electronic questionnaire; data from 154 practices, including 759 general practitioners and covering 1,010,452 patients, were collected. RESULTS: Ninety three practices had all their patient records on computer; others had selectively entered data on, for example, only those patients receiving repeat prescriptions. The number of computerised patient records per practitioner ranged from 46 to 2373. Altogether 194,261 patients had repeat prescribing data and 204,005 morbidity or clinical data. CONCLUSION: An electronic questionnaire is a simple and effective way of investigating the information held on practice computers, allowing analysis and feedback of information to practitioners. Development of this system will provide a cumulative information system for Scottish general practitioners.

Computers↗
PubMed1990

Identification of conserved domains in the cell attachment proteins of the three serotypes of reovirus.

Sequence analysis of reovirus serotype 1 (ST1) and 2 (ST2) S1 genome segment cDNAs identified several differences from previously reported versions of their sequences. The sequences reported here comprise 1463 and 1440 base pairs, respectively; for comparison, the ST3 S1 genome segment is 1416 nucleotides long. The serotype 1 and 2 sigma 1 proteins are predicted to contain 470 and 462 amino acids, respectively; the ST3 sigma 1 protein is 455 amino acids long. As previously observed, the ST1 and ST2 sigma 1 proteins are much more closely related to each other than to that of ST3 (about 48 and 25% similarity, respectively, using a computer program that finds about 14% similarity among unrelated proteins). The sequences of the three S1 genome segments have diverged very extensively in all three codon positions, in some cases almost to the extent of randomness. Despite this, not only function but also shape and configuration have been retained (since the three sigma 1 proteins can be incorporated efficiently into completely heterologous capsids). Seventy-nine amino acid residues are conserved among all three serotypes, many of them clustered into five regions in which one-third or more of the residues are triply conserved. These regions may represent functionally conserved domains involved in oligomerization, cell attachment, and hemagglutination.

Amino Acid Sequence↗
PubMed1990

Effect of starvation and diabetes on the activity of the eukaryotic initiation factor eIF-2 in rat skeletal muscle.

The ability of the initiation factor eIF-2 in skeletal muscle extracts to form ternary initiation complexes ([Met-tRNA(f).eIF-2.GDP]) is decreased by either starvation or diabetes. These conditions also impair the ability of muscle extracts to dissociate [eIF-2.GDP], suggesting inhibition of the guanine nucleotide exchange reaction essential for eIF-2 recycling. We could not, however, detect any change in the phosphorylation state of the alpha subunit of eIF-2. This suggests that eIF-2 activity may be regulated in this system by a mechanism not involving its phosphorylation.

Animals↗
PubMed1990

Hepatitis C infection in two urban hemodialysis units.

We determined the prevalence of antibodies to the hepatitis C virus (anti-HCV) in 90 patients and 37 staff members of two hemodialysis units utilizing a recently developed anti-HCV recombinant based assay. Eleven patients (12%) were anti-HCV(+). Of these, eight (73%) had antibodies to the hepatitis B core antigen (anti-HBc) indicating prior hepatitis B infection; one patient was hepatitis B surface antigen (HBsAg)(+). All staff members were anti-HCV(-), although seven (19%) of them were anti-HBc(+). Alanine aminotransferase elevations were present at the time of the study in four anti-HCV(-) patients and in only one anti-HCV(+) patient. All anti-HCV(+) (mean 59 +/- 74; range 3 to 269 units) and 85% of anti-HCV(-) patients (mean 16 +/- 27; range 0 to 204 units) had received multiple blood transfusions (P = 0.348). Among 50 patients tested for human immunodeficiency virus (HIV), 43% of anti-HCV(+) as compared to only 7% anti-HCV(-) were positive (P = 0.003). There was a history of intravenous drug abuse (IVDA) in eight (72%) of the anti-HCV(+) patients and in only seven (9%) of the anti-HCV(-) group (P = 0.00001). The results of this serologic survey suggests that anti-HCV positivity is prevalent, although much less than anti-HBc, among our dialysis patients, whereas it was not detected among staff members. The prevalence rate of anti-HCV was statistically significantly higher among anti-HIV(+) and IVDA patients but not in multi-transfused patients.

Adult↗
PubMed1990

Osteoclast cytosolic calcium, regulated by voltage-gated calcium channels and extracellular calcium, controls podosome assembly and bone resorption.

The mechanisms of Ca2+ entry and their effects on cell function were investigated in cultured chicken osteoclasts and putative osteoclasts produced by fusion of mononuclear cell precursors. Voltage-gated Ca2+ channels (VGCC) were detected by the effects of membrane depolarization with K+, BAY K 8644, and dihydropyridine antagonists. K+ produced dose-dependent increases of cytosolic calcium ([Ca2+]i) in osteoclasts on glass coverslips. Half-maximal effects were achieved at 70 mM K+. The effects of K+ were completely inhibited by dihydropyridine derivative Ca2+ channel blocking agents. BAY K 8644 (5 X 10(-6) M), a VGCC agonist, stimulated Ca2+ entry which was inhibited by nicardipine. VGCCs were inactivated by the attachment of osteoclasts to bone, indicating a rapid phenotypic change in Ca2+ entry mechanisms associated with adhesion of osteoclasts to their resorption substrate. Increasing extracellular Ca2+ ([Ca2+]e) induced Ca2+ release from intracellular stores and Ca2+ influx. The Ca2+ release was blocked by dantrolene (10(-5) M), and the influx by La3+. The effects of [Ca2+]e on [Ca2+]i suggests the presence of a Ca2+ receptor on the osteoclast cell membrane that could be coupled to mechanisms regulating cell function. Expression of the [Ca2+]e effect on [Ca2+]i was similar in the presence or absence of bone matrix substrate. Each of the mechanisms producing increases in [Ca2+]i, (membrane depolarization, BAY K 8644, and [Ca2+]e) reduced expression of the osteoclast-specific adhesion structure, the podosome. The decrease in podosome expression was mirrored by a 50% decrease in bone resorptive activity. Thus, stimulated increases of osteoclast [Ca2+]i lead to cytoskeletal changes affecting cell adhesion and decreasing bone resorptive activity.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Tc99m HM-PAO single photon emission computed tomography in temporal lobe epilepsy.

We present the results of single photon emission computed tomography (SPECT) in 40 patients with temporal lobe epilepsy and normal computed transmission tomography (CT). Abnormalities of regional cerebral blood flow were found in 26 patients. There was focal hypoperfusion alone in 14, focal hyperperfusion alone in 6, and both types of abnormality in 6. In 4 patients there were bilateral abnormalities. Repeat SPECT showed persistence of interictal hyperperfusion in 5/12 patients. There were no significant correlations between SPECT findings and clinical parameters, and no relation between the persistence of interictal hyperperfusion and time since last seizure or seizure frequency. Where SPECT and multiple surface EEG recordings were both lateralising, agreement between them was good. The results of this study support the usefulness of HMPAO SPECT in detecting lateralising abnormalities in temporal lobe epilepsy. Interictal hyperperfusion may be commoner than previous publications suggest, and may be persistent in some cases.

Adolescent↗
PubMed1990

CT, MR and SPECT imaging in temporal lobe epilepsy.

Cranial computed tomography (CT) with modified temporal lobe technique, 0.15T magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) were carried out on 30 patients with intractable temporal lobe epilepsy. Lateralising abnormalities were detected in 21/30 patients overall. Specific lesions were detected by CT in one patient and by MRI in seven patients (in one case bilateral). In addition CT detected asymmetry of the sylvian fissures or temporal horns in 10 patients, and MRI in eight patients. SPECT detected lateralising abnormalities in 19 patients (in five cases bilateral). It is concluded that low field MRI is superior to modified CT in demonstrating subtle structural lesions of the temporal lobe. Functional scanning with SPECT supports the evidence of origin of an epileptic focus in a substantial proportion of cases and may improve the selection of patients for surgery.

Adolescent↗
PubMed1990

Release of macromolecules and daunomycin from hydrophilic gels containing enzymatically degradable bonds.

The synthesis of hydrophilic gels based on N-(2-hydroxypropyl)methacrylamide copolymers crosslinked via degradable oligopeptide sequences is described. The influence of the conditions of preparation and of the gel structure on the equilibrium degree of swelling (network density) was determined. To evaluate the potential of such gels for controlled delivery of macromolecules and drugs, the release of FITC-dextrans of different molecular weights was studied and the rate of release was found to depend mainly on the equilibrium degree of swelling and not on the structure of the crosslinks. However, the degradation of the gels by a mixture of lysosomal enzymes isolated from rat liver (Tritosomes) or chymotrypsin was dependent on both the equilibrium degree of swelling and the structure of the crosslinks (length of the oligopeptide sequence and structure of the amino acid residues). The release of the anticancer drug daunomycin imbibed in gels was pH-dependent, the rate of release being higher at lower pH. In addition, a gel was synthesized which contained a pentapeptide in the crosslinks and daunomycin bound via a tetrapeptide side-chain, and in this case, incubation with Tritosomes led to degradation with simultaneous release of the drug.

Amino Acid Sequence↗
PubMed1990

Correlates of atherosclerosis in coronary arteries of patients undergoing angiographic evaluation.

The correlations between lipid and lipoprotein measurements and other risk factors of coronary artery disease were evaluated in 101 men undergoing coronary angiography. Clinically significant disease was present in 75 patients, whereas 24 had no observable lesions and 2 had minimal lesions. Comparisons of individual lipid and lipoprotein levels were nearly all significantly different between patients with and patients without clinically significant disease; however, no single variable could predict the presence of disease among patients. Logistic regression analysis identified five factors: apolipoprotein A-I, apolipoprotein B, diabetes, age, and family history of heart disease, which account for most of the differences between the two patient groups. These results could have important implications for the evaluation and management of patients suspected of having coronary atherosclerosis.

Age Factors↗
PubMed1990

Stability of ranitidine hydrochloride at dilute concentration in intravenous infusion fluids at room temperature.

The stability of ranitidine at low concentration (0.05 mg/mL) in five intravenous infusion solutions (0.9% sodium chloride, 5% dextrose, 10% dextrose, 5% dextrose with 0.45% sodium chloride, and 5% dextrose with lactated Ringer's injections) was studied. Admixtures were stored for seven days at room temperature in 150-mL and 1-L polyvinyl chloride infusion bags. Ranitidine stability in 0.9% sodium chloride injection and in 5% dextrose injection was also examined for up to 28 days, and these data were compared with data obtained at higher ranitidine concentrations (0.5-2.0 mg/mL). At intervals during the storage periods, color, clarity, and solution pH were examined and ranitidine content was determined by a stability-indicating high-performance liquid chromatographic assay. Ranitidine content remained greater than 90% of the initial concentration for more than 48 hours in all infusion fluids except 5% dextrose with lactated Ringer's injection. No visual changes or appreciable changes in pH were observed for any of the solutions. At the dilute concentration, ranitidine was markedly more stable after eight hours in 0.9% sodium chloride injection than in 5% dextrose injection. In 0.9% sodium chloride injection, ranitidine concentrations remained above 95% for up to 28 days, but drug concentrations in 5% dextrose injection fell below 90% after seven days. Stability in 5% dextrose injection improved as ranitidine concentrations increased from 0.05 to 2.0 mg/mL. Ranitidine (0.05 mg/mL) is stable for at least 48 hours at room temperature in all infusion fluids tested except 5% dextrose with lactated Ringer's injection.

Chromatography, High Pressure Liquid↗
PubMed1989

Long-term danazol therapy in autoimmune thrombocytopenia: unmaintained remission and age-dependent response in women.

STUDY OBJECTIVE: To assess the long-term benefit and side effects of danazol therapy, and to delineate factors influencing the responses in patients with autoimmune thrombocytopenia. DESIGN: Before and after trial. SETTING: Referral-based hematology clinics and the University of Miami teaching hospitals. PATIENTS: Data were collected on 96 patients (60 women and 36 men, 45 of whom had had splenectomies) receiving danazol therapy for autoimmune thrombocytopenia and analyzed. INTERVENTION: Danazol was added to the previous therapy or begun as an initial therapy. Glucocorticoids were tapered gradually. MEASUREMENTS AND MAIN RESULTS: The overall response rate to danazol was 61.4%. Among responders, the platelet counts (mean +/- SD) before and after danazol treatment were 36 +/- 24 x 10(9)/L and 145 +/- 77 x 10(9)/L, respectively, and the time to response was 2.7 +/- 3 months. Sex, age, and the status of the spleen (absent or present) influenced the responses to danazol. In women, but not in men, response rates improved with advancing age, especially in the nonsplenectomized women. This may be because estrogen levels are high in younger women and low in older women and men. Danazol, when given longer than a year, induced remissions lasting for years even after its discontinuation, but early relapses were frequent when danazol was administered for less than 6 months. Platelet-associated IgG returned to normal range during unmaintained remission. CONCLUSION: Danazol is best suited for long-term medical management of autoimmune thrombocytopenia. It is well tolerated, and lasting, unmaintained remissions often occur after prolonged danazol administration. Age, sex, and the status of the spleen influence the responses. When danazol therapy is used, glucocorticoids can be substantially reduced in dosage or withdrawn. Danazol is a good alternative to splenectomy in elderly persons, especially in women.

Adolescent↗
PubMed1989

Evaluation of protein-N-(2-hydroxypropyl)methacrylamide copolymer conjugates as targetable drug carriers. 1. Binding, pinocytic uptake and intracellular distribution of transferrin and anti-transferrin receptor antibody conjugates.

The transferrin receptor of human skin fibroblasts was studied as an in vitro model target antigen receptor for interaction with protein-polymer conjugates having potential for targeted drug delivery. Pinocytic uptake of 125I-labelled N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugated to monoclonal antibody B3/25 (specific for the transferrin receptor) or transferrin was up to 9-fold greater than uptake of the parent HPMA copolymer. The ability of these conjugates to bind specifically was confirmed by Scatchard analysis. Pinocytic internalisation was dependent on the molecular mass of the conjugate. Intracellular routing following internalisation was evaluated using density-gradient centrifugation. Unmodified HPMA copolymer was transferred via the endosomal compartment into secondary lysosomes, where, being resistant to degradation, it accumulated. Although the majority of endocytosed transferrin is recycled via the endosome, it was shown that any transferrin reaching the lysosomes was rapidly degraded and low-molecular-weight degradation products were released. Monoclonal antibody B3/25 showed a subcellular distribution consistent with prolongation on the cell surface, followed by internalisation and subcellular trafficking, via endosomes, into the lysosomal compartment, with subsequent degradation. Conjugation of protein to HPMA copolymer increased lysosomal accumulation of polymer up to 9-fold, with no detectable degradation of conjugate. The data presented here have implications regarding clinical potential of protein-HPMA copolymer conjugates designed for lysosomotropic drug delivery.

Acrylamides↗
PubMed1989

Voltage-activated and stretch-activated Ba2+ conducting channels in an osteoblast-like cell line (UMR 106).

Calcium entry may mediate osteoblast activation by calciotropic hormones or changes in electrical fields or mechanical stress in bone. Using cell-attached patch clamping techniques, we have seen two Ba2+ conducting channels in UMR-106 osteoblast-like cells: (i) a voltage-dependent, dihydropyridine-sensitive channel resembling L-type Ca2+ channels in other cells, and (ii) a stretch-activated non-selective channel resembling those involved in mechanoreception and triggering of volume regulation in other cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Expression in Escherichia coli of the major outer capsid protein of infectious pancreatic necrosis virus.

The outer capsid polypeptide, VP2, represents the major neutralizing antigen of infectious pancreatic necrosis virus (IPNV). A 926-bp viral cDNA, encoding an N-terminal truncated VP2, was cloned into the pWR590 expression plasmid family resulting in a C-terminal extension of a truncated Escherichia coli beta-galactosidase (beta Gal) under the control of the lac promoter. When cells transformed by in-phase hybrid plasmids were induced by isopropylthiogalactoside, high levels of the 100-kDa beta Gal-VP2 fusion protein accumulated within 4 h after induction. The fusion protein reacted in Western blots both with rabbit anti-beta Gal and with neutralizing mouse anti-VP2 monoclonal antibody. Sera of rabbits immunized with semipurified fusion protein reacted with the VP2 polypeptide in Western blots and with intact purified virus in ELISA and also neutralized IPNV infectivity in a plaque-reduction assay. Out-of-phase hybrid plasmids did not produce the fusion protein but expressed a small amount of structurally discrete VP2-specific sequences probably by internal initiation of translation at an in-phase AUG codon near the 5' end of the VP2 gene.

Amino Acid Sequence↗
PubMed1989

Effect of galactose on interaction of N-(2-hydroxypropyl)methacrylamide copolymers with hepatoma cells in culture: preliminary application to an anticancer agent, daunomycin.

A series of copolymers were prepared containing 1,2:3,4-di-O-isopropylidene-6-O-methacryloyl-alpha-D-galactopyranose (0 to 99 mol %), methacryoyltyrosinamide and N-(2-hydroxypropyl)methacrylamide (99 to 0 mol %). The effect of galactose content on interaction with hepatoma cells in vitro was studied. Increased galactose content caused increased accumulation of N-(2-hydroxypropyl)methacrylamide copolymers by two human hepatoma cell lines (Hep G2 and SAH), but accumulation by rat and mouse hepatoma (HTC and NCTC) was not galactose dependent. Accumulation of N-(2-hydroxypropyl)methacrylamide copolymers by Hep G2 was shown to be an active process, being inhibited by low temperature and by the metabolic inhibitor 2,4-dinitrophenol. Addition of N-acetylgalactosamine and polymer-galactose to the incubation medium resulted in a concentration-dependent inhibition of accumulation of galactose-containing polymers. Addition of fucose or galactose was without effect at the concentrations used. Polymers bearing galactosamine or fucosylamine residues and, in addition, daunomycin were evaluated for cytotoxicity against Hep G2 and SAH. N-(2-Hydroxypropyl)methacrylamide copolymer-bound daunomycin produced a dose-dependent inhibition of DNA synthesis (measured by incorporation of [3H]thymidine), and the galactose-containing polymer showed greatest inhibition.

Acrylamides↗