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Biomedical subjects

D Donaldson

Publications and source records attributed to D Donaldson.

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

Lessons to be learned: a case study approach. Vitamin B12 deficiency of nutritional origin.

The case is presented of a 14 year old boy who developed severe anaemia at the onset of puberty caused by nutritional deficiency of vitamin B12 of about 10 years duration. The dietary intake comprised mainly chips, ice-cream, fruit and Coca-Cola--with small amounts of vitamin B12 from occasional slices of chicken meat. His denial of abnormal nutritional intake, supported by his mother, delayed confirmation of the correct diagnosis. However, the true situation was eventually confessed--and following implementation of a normal diet he rapidly improved clinically, the haemoglobin value rose to normal and he subsequently remained well.

Adolescent↗
PubMed1997

Lessons to be learned: a case study approach. Severe hypoglycaemia in insulin-dependent diabetes mellitus (IDDM)--living to tell the tale.

The case is presented of a 62 year old doctor with insulin-dependent diabetes mellitus (IDDM) who experienced severe nocturnal hypoglycaemia following a total intake for the day of fruit and yoghurt (providing 230 kcal) for breakfast, four pints of beer (providing 540 kcal-which included the energy from 37.0 g carbohydrate) later in the day and an evening meal containing approximately 123 g of carbohydrate (providing 1050 kcal). He had taken insulin, as was his custom, just before breakfast, half-an-hour prior to the evening meal and again two-and-a-half hours afterwards. He felt entirely well when he retired to bed at 2100 h. He awoke later, having dreamt that he was practically immobile-but then found to his horror that the dream was true. He soon realised that he was severely hypoglycaemic and, as he had no glucose immediately available, had no alternative but in some way to attempt the journey to the kitchen where there was non-diet mandarin drink available in tin cans inside a refrigerator. He was able later to recall and, in consequence, describe the whole terrifying experience in great detail, on account of the remarkable preservation of mental clarity. The clinical features of the episode are viewed in terms of the relationships between alcohol intake, carbohydrate ingested and the insulin administered. Exercise was minimal on this day.

Alcoholic Beverages↗
PubMed1997

Effects of ifenprodil, a polyamine site NMDA receptor antagonist, on reperfusion injury after transient focal cerebral ischemia.

Polyamines and N-methyl-D-aspartate (NMDA) receptors are both thought to play an important role in secondary neuronal injury after cerebral ischemia. Ifenprodil, known as a noncompetitive inhibitor of polyamine sites at the NMDA receptor, was studied after transient focal cerebral ischemia occurred. Spontaneously hypertensive male rats, each weighing between 250 and 350 g, underwent 3 hours of tandem middle cerebral artery (MCA) and common carotid artery occlusion followed by reperfusion for a period of 3 hours or 21 hours. Intravenous ifenprodil (10 microg/kg/minute) or saline infusion was started immediately after the onset of MCA occlusion and continued throughout the ischemic period. Physiological parameters including blood pressure, blood gas levels, blood glucose, hemoglobin, and rectal and temporal muscle temperatures were monitored. Six rats from each group were evaluated at 6 hours postocclusion for brain water content, an indicator of brain edema, and Evans blue dye extravasation for blood-brain barrier breakdown. Infarct volume was also measured in six rats from each group at 6 and 24 hours postocclusion. Ifenprodil treatment significantly reduced brain edema (82.5 +/- 0.4% vs. 83.5 +/- 0.4%, p < 0.05) and infarct volume (132 +/- 14 mm3 vs. 168 +/- 25 mm3, p < 0.05) compared with saline treatment, with no alterations in temporal muscle (brain) or rectal (body) temperature (35.9 +/- 0.4 degrees C vs. 36.2 +/- 0.2 degrees C; 37.7 +/- 0.4 degrees C vs. 37.6 +/- 0.6 degrees C; not significant). These results demonstrate that ifenprodil has neuroprotective properties after ischemia/reperfusion injury in the absence of hypothermia. This indicates that antagonists selective for the polyamine site of the NMDA receptors may be a viable treatment option and helps to explain some of the pathophysiological mechanisms involved in secondary injury after transient focal cerebral ischemia has occurred.

Adrenergic alpha-Antagonists↗
PubMed1996

Brain superoxide dismutase, catalase, and glutathione peroxidase activities in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a fatal paralytic disorder of unknown cause. Recent evidence implicated the role of free radicals in the death of motor neurons in this disease. To investigate this hypothesis further, we measured the activity of the main free radical scavenging enzymes copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase in postmortem brain samples from 9 patients with sporadic amyotrophic lateral sclerosis and from 9 control subjects. We examined samples from the precentral gyrus of the cerebral cortex, a region affected in amyotrophic lateral sclerosis, and from the cerebellar cortex, a region not affected. The two groups did not differ in age or postmortem delay. In the precentral gyrus from amyotrophic lateral sclerosis samples, glutathione peroxidase activity as measured by spectrophotometric assay (13.8 +/- 2.6 nmol/min/mg protein [mean +/- standard error of mean]) was reduced significantly compared to the activity in the precentral gyrus from control samples (22.7 +/- 0.5 nmol/min/mg protein). In contrast, glutathione peroxidase activity was not significantly altered in the cerebellar cortex from amyotrophic lateral sclerosis patients compared to controls. Copper/zinc superoxide dismutase, manganese superoxide dismutase (corrected or not corrected for citrate synthase), and catalase were not significantly altered in the precentral gyrus or cerebellar cortex in the patient samples. This study indicated that glutathione peroxidase activity is reduced in a brain region affected in amyotrophic lateral sclerosis, thus suggesting that free radicals may be implicated in the pathogenesis of the disease.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Delayed hyperglycemia and intracellular acidosis during focal cerebral ischemia in cats.

The effects of hyperglycemia on permanent focal brain ischemia is controversial; its effects on the size of the infarct are variable according to experimental conditions. In this study, nuclear magnetic resonance (NMR) spectroscopy was used to assess brain pH and high-energy phosphate metabolites after focal middle cerebral artery (MCA) ischemia in hyperglycemic and normoglycemic cats. Sixteen adult cats underwent (MCA) occlusion under general anesthesia and nuclear magnetic resonance 31P spectroscopy to assess intracellular brain pH and energy metabolites throughout permanent ischemia. Animals were treated two hours after the onset of ischemia with either saline or glucose perfusions. Significant hyperglycemia (488 vs 105 mg/100 ml) was achieved in the experimental group. The response to hyperglycemia was dependent on the initial characteristics of the infants. A distinct pattern of phosphocreatine/inorganic phosphate recovery within 20 minutes of ischemia predicted a small infarct size. The addition of hyperglycemia did not affect acidosis, infarct size, or metabolite ratios in these animals. The lack of phosphocreatine/inorganic phosphate recovery within 20 minutes of ischemia was predictive of an eventual large infarct. In these animals, the delayed addition of hyperglycemia significantly lowered intracellular pH during the ischemic period (5.45 vs. 6.25, p = 0.25). These data support the theory that the response to hyperglycemia is very dependent on the initial metabolic state of the injured brain. This state can be predicted by early 31P spectroscopy data, which may, in turn, prove to be a useful marker for recoverable ischemic deficit in the cerebral region of interest.

Acid-Base Equilibrium↗
PubMed1996

Leximin population ethics.

This paper concerns the ethical issues that arise when policy decisions have to be taken that affect population size and characteristics. Such policies include social security systems, intertemporal resource allocation decisions, and policies designed to influence fertility rates. The authors provide characterizations of Leximin principles for social evaluation in an intertemporal framework, so that they can be used to compare social alternatives with different population sizes. "The main axioms used in our characterizations are Hammond Equity together with Independence of the Utilities of the Dead (a plausible intertemporal consistency requirement) for the Critical-Level Leximin principles, and Positional Leximin Consistency (an axiom that allows non-constant critical levels) for the Positional-Extension Leximin principle. The performance of these principles is compared in the pure population problem and we argue that the Critical-Level Leximin principles are ethically more attractive than Positional-Extension Leximin."

Demography↗
PubMed1996

Enhanced accumulation of free fatty acids in experimental focal cerebral ischemia.

Cerebral ischemia is well known to cause an increase in the level of free fatty acids (FFAs) in rodent species. Such FFA accumulations may signal regional lipid membrane damage and are postulated to participate in the pathogenesis of progressive infarction after cerebral ischemia. In this study we have examined the regional levels of FFAS in the cortices of cats after 8 h of middle cerebral artery occlusion. The levels of specific FFAs (palmitic, stearic, and oleic acids) were 1.5 and 2.0 times higher in the penumbral and dense ischemic regions, respectively, than those in the non-ischemic contralateral region. Although no significant differences were found between the penumbra and dense ischemic regions in the levels of arachidonic acid, the levels of docosahexaenoic acid in both of these regions were significantly higher than those in the contralateral region (P < 0.05). These results suggest that enhanced accumulation of FFAs are regionally distributed after focal ischemia and may contribute to neuronal damage after focal cerebral ischemia in non-rodent species.

Animals↗
PubMed1996

Effect of hyperglycemia on reperfusion-associated recovery of intracellular pH and high energy phosphates after transient cerebral ischemia in gerbils.

Hyperglycemia increases cerebral damage after transient cerebral ischemia. This study used in vivo 31P nuclear magnetic resonance spectroscopy to determine the relationship of intracellular tissue acidosis and delayed recovery of brain high-energy phosphates to increased damage during the reperfusion period. Mongolian gerbils were subjected to transient bilateral carotid ischemia for 20 min with 2 h reperfusion. All gerbils were pretreated intraperitoneally with equivalent volumes in saline of 0.003 units per kilogram of insulin or vehicle, or with 4 grams of glucose per kilogram. The gerbils were then scanned in a 4.7 Tesla Magnetic Resonance Imager-Spectrometer to determine levels of intracellular pH, inorganic phosphate, adenosine triphosphate, and phosphocreatine. In each group, intracellular pH decreased with ischemia, but most significantly in hyperglycemic animals (6.45 +/- 0.15), in which it had not recovered to preischemic levels by the end of the reperfusion period (6.8 +/- 0.1 vs 7.04 +/- 0.1, p < 0.05). High-energy phosphates phosphocreatine-inorganic phosphate and phosphocreatine-adenosine triphosphate showed partial recovery in all groups throughout the reperfusion period; the recovery was not significantly altered by glucose status. Hyperglycemia worsened pH but not the recovery of high-energy phosphates in animals reperfused after 20 min of transient cerebral ischemia. This sustained acidosis may be a primary event in transient damage in hyperglycemic animals.

Adenosine Triphosphate↗
PubMed1996

Physical and sexual abuse and their relation to psychiatric disorder and suicidal behavior among adolescents who are psychiatrically hospitalized.

Adolescents who were psychiatrically hospitalized (N = 105) were classified as sexually abused, physically abused, both sexually and physically abused, or not abused, and studied to determine the prevalence of suicidal behavior and psychiatric disorders. Self-reports of hopelessness, depression, coping, and self-concept were also examined. No difference in suicidal behavior or psychiatric disorder, based on abuse history, was found, with one exception. Adolescents who were sexually abused, particularly those who experienced the most severe sexual abuse, used negative coping strategies more often than those not sexually abused. Findings suggest that symptomatology of adolescents who are psychiatrically hospitalized does not differ markedly based on history of abuse.

Adaptation, Psychological↗
PubMed1996

Protective effect of the 5-lipoxygenase inhibitor AA-861 on cerebral edema after transient ischemia.

This study examined the effect of AA-861, a specific 5-lipoxygenase inhibitor, on brain levels of leukotriene C4 (LTC4) and correlated any changes with changes in edema formation and cerebral blood flow (CBF) after transient ischemia in gerbils. Brain levels of LTC4 were observed to be increased at 1, 2, and 6 hours of reperfusion following 20 minutes of occlusion. At 2 hours of reperfusion, a pretreatment dose of 1000 mg/kg of AA-861 was required to inhibit more than 90% of the reperfusion-induced increases in brain LTC4. At this dose, inhibition of LTC4 production was observed at 2 and 6 hours of reperfusion. The specific gravity of both the cortex and subcortex was decreased at 6 hours of reperfusion after 20 minutes of occlusion. At 2 hours of reperfusion, no significant difference was observed in the specific gravity of the cortex and subcortex regions of gerbils pretreated with AA-861 or with vehicle, but at 6 hours of reperfusion significant positive differences were observed. Cerebral blood flow decreased to approximately 10% of preocclusion values during occlusion and returned to near-preocclusion values after 10 minutes of reperfusion. No significant differences were observed in regional CBF in the AA-861- and vehicle-pretreated gerbils during reperfusion. These findings indicate that LTC4 production after transient cerebral ischemia may be an important contributor to the development of cerebral edema and that CBF does not mediate the LTC4-involved development of edema.

Animals↗
PubMed1996

Interleukin-4 (IL-4) in combination with IL-11 or IL-6 reverses the inhibitory effect of IL-3 on early B lymphocyte development.

We have previously described a two-step methylcellulose culture system in which individual primitive progenitors from 5-fluorouracil (5-FU)-treated mice were shown to have both myeloid and B lymphoid differentiation capacity. Highly enriched Lin-Sca+FU2d BM cells were cultured in methylcellulose in the presence of Steel factor (SF), interleukin-7 (IL-7), and pokeweed mitogen stimulated spleen cell conditioned medium (PWM-SCM). Primary mixed myeloid colonies were replated after 8-11 days into secondary cultures containing SF and IL-7, which supported the generation of B220+sIgM- pre-B cell colonies. A number of growth factors, including IL-6, IL-11, granulocyte colony-stimulating factor (G-CSF), and IL-12 were shown to be capable of substituting for PWM-SCM to support the B lymphoid potential of primary colonies. B lymphoid potential was not supported, however, in SF + IL-3 or in SF + IL-3 plus any single growth factor (IL-1 to -12, granulocyte-macrophage colony-stimulating factor [GM-CSF], G-CSF, erythropoietin [Epo], leukemia inhibitory factor [LIF], tumor necrosis factor-alpha [TNF-alpha], transforming growth factor-beta [TGF-beta], gamma interferon [IFN-gamma], or insulin-like growth factor-1 [IGF-1]), but was supported in SF + IL-3 + 5% PWM-SCM. Experiments were designed to identify the factor or factors in PWM-SCM that reverse the inhibitory effects of IL-3 on B lymphoid potential. By substituting various cytokine combinations for PWM-SCM, we determined that combinations of IL-4 + IL-6 or IL-4 + IL-11, but not IL-4 alone, can substitute for PWM-SCM to reverse the inhibitory effect of IL-3 on B lymphoid potential. Neutralizing antibodies to IL-4 completely eliminated the activity in PWM-SCM, but antibodies to IL-6 only partially inhibited the activity. IL-11 was not detected in PWM-SCM, and the activity co-purified with IL-4, but not with IL-6. Thus, IL-4 plus IL-6, IL-11, or one or more unidentified growth factors in PWM-SCM can reverse the inhibitory effects of IL-3 on early B lymphocyte development in culture.

Animals↗
PubMed1995

The hazards of chronic exposure to nitrous oxide: an update.

This paper reviews the potential occupational hazards associated with chronic exposure to nitrous oxide. The evidence that chronic exposure to the gas produces problems related to reproduction in dental personnel is convincing. Recent evidence suggests that scavenging systems decrease the adverse effects which nitrous oxide has on fertility of dental surgery assistants. However, even in the presence of scavenging systems trace levels of the gas can exceed recommended minimum levels.

Air Pollution, Indoor↗
PubMed1995

Molecular analysis and breakpoint definition of a set of human chromosome 21 somatic cell hybrids.

Rodent-human somatic cell hybrids containing single human chromosomes or chromosome fragments are extremely valuable in physical mapping, marker analysis, and disease mapping. Chromosome 21 has been extensively studied in this fashion, and a single set of hybrids has been utilized in mapping the majority of chromosome 21 markers. The utility of a set of hybrids depends upon the definition of the human chromosome content. Recently, Chumakov and coworkers (1) utilized 198 chromosome 21 markers in the preliminary analysis of YACs spanning chromosome 21q. We have used these same markers to evaluate the STS content of a set of 27 chromosome 21 somatic cell hybrids, resulting in the description of the breakpoints at the molecular level, as well as the definition of 35 "bins. " The detailed molecular definition of chromosome 21 content of the hybrids, in combination with the further analysis of chromosome 21 YACs (2), has resulted in the most detailed picture of chromosome 21 to date.

Animals↗
PubMed1995

Effect of gestational age on levels of serum alkaline phosphatase isoenzymes in healthy pregnant women.

OBJECTIVES: To confirm that the bone isoenzyme of alkaline phosphatase (ALP) contributes significantly to the increased ALP in normal pregnancy, and to determine the gestational age at which the increase occurs. METHODS: Cross-sectional determinations of serum total, bone and placental ALP were carried out in 67 normal pregnant women. The results were compared with those of 18 normal age-matched non-pregnant controls using Student's t-test. RESULTS: At both 31-32 weeks and 38 weeks of gestation, serum activities of bone ALP were increased significantly (P < 0.05 and P < 0.001, respectively) when compared with controls. The percentage contribution of bone ALP to the total was higher at 31-32 weeks and lower at 38 weeks when compared with the contribution from placental ALP. CONCLUSION: Knowledge of time of elevation of serum bone ALP activity in normal pregnancy will be helpful in the interpretation of elevated serum total ALP activity during pregnancy.

Adult↗
PubMed1995

Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by intrastriatal injection of 6-hydroxydopamine.

Animal models with partial lesions of the dopaminergic nigrostriatal pathway may be useful for developing neuroprotective and neurotrophic therapies for Parkinson's disease. To develop such a model, different doses of 6-hydroxydopamine (0.0, 0.625, 1.25, 2.5 and 5.0 micrograms/microliters in 3.5 microliters of saline) were unilaterally injected into the striatum of rats. Animals that received 1.25 to 5.0 micrograms/microliters 6-hydroxydopamine displayed dose-dependent amphetamine and apomorphine-induced circling. 6-Hydroxydopamine also caused dose-dependent reductions in [3H]mazindol-labeled dopamine uptake sites in the lesioned striatum and ipsilateral substantia nigra pars compacta (up to 93% versus contralateral binding), with smaller losses in the nucleus accumbens, olfactory tubercle and ventral tegmental area. In the substantia nigra pars compacta and the ventral tegmental area, the number of Nissl-stained neurons decreases in parallel with the reduction in [3H]mazindol binding. The reduction in [3H]mazindol binding in the striatum and the nucleus accumbens, and the reduction in [3H]mazindol binding and in the number of Nissl-stained neurons in the substantia nigra pars compacta and the ventral tegmental area is stable for up to 12 weeks after the lesion. Macroscopically, forebrain coronal sections showed normal morphology, except for rats receiving 5.0 micrograms/microliters 6-hydroxydopamine in which striatal cross-sectional area was reduced, suggesting that this high dose non-specifically damages intrinsic striatal neurons. Nissl-stained sections revealed an area of neuronal loss and intense gliosis centered around the needle track, which increased in size with the dose of neurotoxin. Striatal [3H]sulpiride binding was increased by 2.5 micrograms/microliters and 5.0 micrograms/microliters 6-hydroxydopamine, suggesting up-regulation of dopamine D2 receptors. Striatal binding of [3H]CGS 21680-labeled adenosine A2a receptors, but not of [3H]SCH 23390-labeled dopamine D1 receptors, was reduced at the highest dose, suggesting preservation of the striatal intrinsic neurons with the lower doses. This study indicates that intrastriatal injection of different doses of 6-hydroxydopamine can be used to cause increasing amounts of dopamine denervation, which could model Parkinson's disease of varying degrees of severity. Injecting 3.5 microliters of 2.5 micrograms/microliters 6-hydroxydopamine appears to be particularly useful as a general model of early Parkinson's disease, since it induces a lesion characterized by robust drug-induced rotation, changes in binding consistent with approximately 70% dopamine denervation, approximately 19% dopamine D22 receptor up-regulation, negligible intrinsic striatal damage and stability for at least 12 weeks. This study outlines a technique for inducing partial lesions of the nigrostriatal dopamine pathway in rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Intertemporal population ethics: critical-level utilitarian principles.

"This paper considers the problem of social evaluation in a model where population size, individual lifetime utilities, lengths of life, and birth dates vary across states. In an intertemporal framework, we investigate principles for social evaluation that allow history to matter to some extent. Using an axiom called independence of the utilities of the dead, we provide a characterization of critical-level generalized utilitarian rules. As a by-product of our analysis, we show that social discounting is ruled out in an intertemporal welfarist environment. A simple population-planning example is also discussed."

Ethics↗