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Biomedical subjects

H McIlwain

Publications and source records attributed to H McIlwain.

At least 19 recordsLinked to original sources
PubMed1996

Comparative study of alendronate versus etidronate for the treatment of Paget's disease of bone.

Alendronate, an aminobisphosphonate, is much more potent than etidronate, an older bisphosphonate, in inhibiting osteoclast-mediated bone resorption, and unlike etidronate, therapeutic doses of alendronate are not associated with abnormal mineralization. In the present study, we compared the effectiveness, safety, and tolerability of 6 months of daily oral administration of alendronate (40 mg) with those of etidronate (400 mg) in 89 patients with clinically active Paget's disease. The primary efficacy end point was the percent change in serum alkaline phosphatase. Other end points included changes in urinary deoxypyridinoline excretion, pain, functional impairment scores, and radiological osteolysis. Tetracycline-labeled bone biopsies were obtained for histomorphometric analysis from a subset of 43 patients at the 6-month visit. The alendronate-treated group had significantly greater decreases in both serum alkaline phosphatase (79% vs. 44%) and urinary deoxypyridinoline (75% vs. 51%) than the etidronate-treated group (P < 0.001 in both cases). Normalization of serum alkaline phosphatase was much more frequent in alendronate-treated patients (63.4% vs. 17.0%; P < 0.001). Alendronate was well tolerated and had a safety profile similar to that of etidronate. Histomorphometry revealed decreased bone turnover and no qualitative abnormalities, including no direct negative effects on bone mineralization, with alendronate treatment. One patient receiving etidronate developed frank osteomalacia. Alendronate appears to be a highly effective treatment for Paget's disease of bone that offers an important therapeutic advance over etidronate.

Administration, Oral↗
PubMed1992

Contributions to neurochemical knowledge considered ecologically.

The development of neurochemical knowledge is traced through the following stages: (1) Beginnings with academic medicine: a dissertation of 1719, (2) Relations with chemistry and scientific journals of around 1800, (3) A review and the naming of neurochemistry in 1856, (4) Government publication of neurochemistry; a full-time chemist of the brain, (5) Success in a biochemical environment, 1900-1940, (6) Neurochemistry with the neurosciences, (7) Neurochemical environments of 1955-1957.

Academies and Institutes↗
PubMed1991

How neurochemistry regained its specific biological components: experimental and cognitive advance, 1935-1955.

Neurochemistry in the 1850s was part of comparative animal chemistry, which became incorporated into physiological chemistry. By 1900, the connection with physiological chemistry had largely lapsed or been vehemently repudiated. Growth of biochemistry, especially from the 1920s to 1950s, provided techniques and findings sufficient to reintegrate chemical knowledge of neural systems with neural functioning. Vitamin, coenzyme, respiratory and other metabolic studies made large contributions to this outcome. Regarding mental illness as a social problem and scientific challenge gave impetus and funds to such work, which resulted in major experimental and cognitive progress.

Animals↗
PubMed1989

Intra-articular orgotein in osteoarthritis of the knee: a placebo-controlled efficacy, safety, and dosage comparison.

PURPOSE: Superoxide dismutase (orgotein for injection) has been used in managing osteoarthritis for more than seven years in Europe; however, well-controlled studies to establish an optimum dosage regimen have not been conducted. In this study, three orgotein dose/regimens were compared with placebo in terms of efficacy, safety, and duration of effect in patients with active osteoarthritis of the knee. PATIENTS AND METHODS: A total of 139 patients with osteoarthritis of the knee were enrolled in the study. Nonsteroidal anti-inflammatory agents were withdrawn to induce a flare of disease activity. Patients were then randomly assigned to receive one intra-articular injection of either placebo or orgotein (8 mg to 32 mg) each week for three weeks. Both investigators and patients evaluated disease activity and adverse experiences at a series of follow-up visits for three months. RESULTS: Orgotein was effective in reducing symptoms of osteoarthritis for up to three months after treatment; 16 mg given twice was the most effective and most best-tolerated regimen. Discomfort at the injection site was drug related, although this effect also occurred occasionally after injection of placebo. CONCLUSION: The long-lasting effects of intra-articular superoxide dismutase contribute to a favorable risk-benefit ratio and support the importance of the free-radical anion, superoxide (O2-), in the biochemical pathology of osteoarthritis.

Aged↗
PubMed1986

Adenosine in cerebral homeostatic role: appraisal through actions of homocysteine, colchicine, and dipyridamole.

Mammalian neocortical tissues were incubated in [14C]adenine-containing fluids and their newly-synthesized adenine derivatives examined after periods of superfusion. Increased [K+] released adenine derivatives from the tissues, a release diminished by homocysteine. Homocysteine acted also to diminish the tissue content of adenosine plus its metabolites hypoxanthine and inosine, while increasing that of S-adenosylhomocysteine. Hypoxia also increased the tissue content and the output of adenosine plus its metabolites, and again homocysteine augmented the S-adenosylhomocysteine. Glutamic acid also increased tissue content and output of adenosine and derivatives, an action diminished by homocysteine and associated with augmented S-adenosylhomocysteine. Colchicine or dipyridamole did not prevent augmentation of S-adenosylhomocysteine by the reagents described; the sequence from adenosine phosphates to S-adenosylhomocysteine is concluded to be intracellular and not to involve extracellular formation of precursor adenosine. Adenosine displayed properties consistent with its being involved in two distinct categories of homeostasis, and also with its exerting an inhibitory tone in normal cerebral systems.

Adenine↗
PubMed1986

The origin and use of the terms competitive and non-competitive in interactions among chemical substances in biological systems.

The terms competition and competitive were in use for appropriate types of interaction in human and animal behaviour from the seventeenth century. In the nineteenth and early twentieth centuries they reached more technical uses in biology, especially in darwinian studies; and in chemistry in describing competing reactions, surface phenomena and the influence of substituent groupings in reactant molecules. Use of competitive and non-competitive to describe enzyme inhibitors had a specific beginning when J. B. S. Haldane (following premonitory work of others) applied the terms in 1927 and 1930 to types of inhibition already differentiated by Michaelis and co-workers. The theoretical background in kinetics and stereochemistry so acquired gave a firmness to the application of the terms in biochemistry. The first examples concerned glycosidases, especially beta-D-fructofuranosidase or invertase, and interactions of carbon monoxide and oxygen at iron-porphyrin systems. They were thus of interest in toxicology and in enzyme and carrier studies. The sphere of application of the biochemically-defined terms expanded greatly when, following investigation of sulphonamide action, it was realized that concepts of enzyme inhibition by structurally related compounds offered a route to understanding the action of existing medicaments and to the production of new ones. Ideas and terminology based on competitive and non-competitive enzyme inhibition and receptor occupancy have subsequently been applied in many ways. Examples include application to the analysis of feedback inhibition and other processes of metabolic control; to receptor relationships among neurotransmitters and medicaments; and to understanding interactions at sensory receptors.

Animals↗
PubMed1985

Assay-guided isolation of naturally-occurring neuroactive substances.

Ways in which chemical techniques could be applied to the understanding of neural systems, their functioning and their disorders were devised only gradually during the present century. In a particularly successful procedure, now termed assay-guided isolation, neural defects were made good by means of tissue-extracts and the restoration of function was established as an assay-system to guide the chemical separation and identification of the active tissue constituent. Thiamin was so isolated, using an experimental polyneuritis assay; subsequent instances among other metabolites, hormones, neurotransmitters and nerve growth factors are recounted. Procedures of assay-guided characterization ensured that links were retained between specific, sparsely-occurring substances and chosen aspects of their biological roles while their chemical nature was first explored and then established. The procedures discouraged the too-facile postulating of hypothetical molecules and contributed to the distinctiveness of neurochemistry as a subject within the neurosciences.

Animals↗
PubMed1985

In the beginning: to celebrate 20 years of the International Society for Neurochemistry (ISN).

The antecedents of the International Society for Neurochemistry are described, especially the parts played by the International Neurochemical Symposia held between 1954 and 1962; the Journal of Neurochemistry between 1956 and 1965; and by other organizations concerned with neural systems though not primarily neurochemical. Description is also given of the foundation of the Society in 1965 and of its first International Meeting in 1967.

Congresses as Topic↗
PubMed1981

The binding of [3H]adenosine to synaptosomal and other preparations from the mammalian brain.

1. A high-affinity adenosine-binding site with Kd(adenosine) 0.5-1.3 microM was demonstrated in particulate and synaptosomal fractions isolated from the cerebral cortex of guinea pig, rat and ox. 2. Binding of [3H]adenosine to this site was inhibited by theophylline and by 2-chloroadenosine, but not by four other adenosine analogues. 3. Endogenous adenosine, found to be present in some preparations at approx. 1 pmol/mg of protein, diminished the binding capacity of the preparations for [3H]adenosine. 4. Addition of the adenosine deaminase inhibitor erythro-9-[1-(1-hydroxyethyl)heptyl]-adenine revealed the presence of a second lower affinity binding site with Kd (adenosine) 5-9 microM and a higher maximal adenosine-binding capacity. The inhibitor partially blocked binding to the high-affinity site in preparations from which adenosine deaminase had been removed by washing. 5. To preparations of particulate fractions maintained under iso-osmotic conditions, adenosine attachment was non-saturable and temperature-dependent, indicating the existence of an active uptake process. 6. The location and binding constant of the high-affinity adenosine-binding site suggest that it corresponds to the receptor site for adenosine-activated adenylate cyclase.

Adenosine↗
PubMed1981

Cyclic AMP-binding capacities and histone kinase activation in subcellular components of neocortical tissue. Differential responses to three neurohumoural agents.

1. Noradrenaline and histamine, when added to superfused guinea-pig cerebral-cortical tissues, increased both cyclic AMP-dependent and -independent histone kinase activities of some, but not of all, subsequently isolated subcellular fractions, and decreased their cyclic [(3)H]AMP-binding capacity, which was concluded to be due to an increase in endogenously bound cyclic AMP. 2. Adenosine and 2-chloroadenosine also diminished the cyclic [(3)H]AMP-binding capacities, but did not affect the histone kinase activities. 3. DEAE-cellulose chromatography and stability to KCl additions showed that the greater part of the histone kinase of the present preparations corresponded to the type II enzyme [of Corbin, Keely & Park (1975) J. Biol. Chem.250, 218-225], with a lesser amount of type I activity. Different sites of cyclic AMP accumulation in relation to these or other kinases are considered in interpreting the differential tissue responses to the neurohumoural agents examined.

Adenosine↗
PubMed1981

Erythrocyte transketolase activity in the Wernicke-Korsakoff syndrome.

Erythrocyte transketolase activity and the effect of adding thiamine pyrophosphate (% TPP effect) were measured in subjects suffering from Wernicke-Korsakoff syndrome both before and during treatment with thiamine and/or thiamine tetrahydrofurfuryldisulphide (TTFD). Transketolase activity was significantly lower in untreated patients than in healthy volunteers. Treatment with either thiamine or with TTFD restored enzyme levels to control values but TTFD produced a greater increase than thiamine in enzyme activity. In a group of seven patients there was no correlation between duration of TTFD therapy and either increase in erythrocyte transketolase activity or % decrease in the TPP effect. However, when three patients were followed at intervals during treatment with TTFD, their erythrocyte transketolase increased progressively. Neither thiamine nor TTFD produced clinical improvement in the mental symptoms of Wernicke-Korsakoff psychosis unless administered early in the course of the disease.

Alcohol Amnestic Disorder↗
PubMed1981

Wernicke-Korsakoff syndrome in monozygotic twins: a biochemical peculiarity.

A pair of monozygotic twins, one suffering from the Wernicke-Korsakoff syndrome, verified at autopsy, and the other healthy, was studied biochemically. The erythrocyte transketolase of each twin showed abnormalities, though these differed in the two individuals. In the healthy twin, the basal transketolase was low, but responded normally to thiamine pyrophosphate (TPP) added in vitro. In the twin with the Wernicke-Korsakoff syndrome the basal level of the enzyme and its response in vitro were normal, but a period of treatment with thiamine tetrahydrofurfuryldisulphide, led to loss of the in vitro response. It is suggested that, initially, an inborn error of metabolism may have been common to both twins.

Alcohol Amnestic Disorder↗
PubMed1980

Erythrocyte transketolase activity in suspected cases of Leigh's disease, or subacute necrotising encephalomyelopathy.

Erythrocyte transketolase activity and the effect of adding thiamine pyrophosphate (% thiamine pyrophosphate effect) were measured in 111 subjects suspected to suffer from Leigh's disease (subacute necrotising encephalomyelopathy). From clinical evidence these subjects were divided into five groups: (1) necropsy-proved cases of subacute necrotising encephalomyelopathy, (2) cases positive for urinary thiamine pyrophosphate: adenosine triphosphate phosphotransferase inhibitor, (3) clinically likely cases of subacute necrotising encephalomyelopathy (patients still alive, or on whom no necropsy was performed), (4) cases diagnosed as diseases other than subacute necrotising encephalomyelopathy (control group), (5) cases for which no diagnosis had been made. Comparison of erythrocyte transketolase activities with and without added thiamine pyrophosphate and of the % thiamine pyrophosphate effect for each group compared with the control group showed no statistically significant differences from normal values for any of these parameters. Similarly, there were no differences between the two sexes in transketolase activity, and no correlation between transketolase activity and age. These results indicate that erythrocyte transketolase activity is not altered in subacute necrotising encephalomyelopathy and is unlikely to be of value for the diagnosis of Leigh's disease.

Brain Stem↗