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Biomedical subjects

D Donaldson

Publications and source records attributed to D Donaldson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Lessons to be learned: a case study approach diuretic therapy and a laxative causing electrolyte and water imbalance, loss of attention, a fall and subsequent fractures of the tibia and fibula in an elderly lady.

The case is described of a hitherto well, alert and intelligent lady of 85 years of age, who commenced medication with diuretics--prescribed for mild congestive cardiac failure; she developed constipation consequent upon the diuresis and dehydration thereby provoked. As a result she began to take, unknown to her general practitioner, regular and increasing amounts of laxatives. At about this time she was noted by her son to become "rapidly senile"--with the result that she fell on account of losing her normally good concentration and attention; she sustained fractures of the right tibia and fibula. Shortly after admission to hospital she was premedicated, anaesthetised and operated upon, following which there was a postoperative regimen comprising several litres of low sodium isotonic infusions, all given intravenously. She was found at this point to be severely hyponatraemic with a low serum osmolality, but following the institution of water restriction rapidly improved as her serum sodium rose again; there was an accompanying massive diuresis as the previously retained water was voided. Concomitant with the serum sodium rise her mental concentration and attention regained their former levels. The biochemical and cellular mechanisms underlying this patient's symptoms are discussed.

Accidental Falls↗
PubMed1998

Lessons to be learned: a case study approach. Finger discoloration due to silver nitrate exposure: review of uses and toxicity of silver in clinical practice.

A 29 year-old lady attended the Accident and Emergency Department of a District General Hospital complaining of increasing black discoloration of the tip of her left middle finger; the appearance resembled that of gangrene. However, it was established that she had been applying silver nitrate to her finger, as prescribed by her general practitioner for the treatment of a small granuloma. Hence, the true diagnosis was of localised tissue necrosis, secondary to application of the silver nitrate sticks. On early discontinuation of the therapy, there was complete recovery. In consequence, it is recommended that the practice of unsupervised local application of silver nitrate to the fingers should be discontinued. Opportunity is taken herein to review the uses of silver nitrate in clinical situations--and of silver in any of its many other forms--together with their respective adverse effects.

Adult↗
PubMed1998

Modifications to the National Dental Examining Board of Canada's certification process.

Following a lengthy and intense consultation with stakeholders, and an analysis of the present certification process, the National Dental Examining Board of Canada (NDEB) and the 10 provincial licensing authorities recently approved major changes to the certification process for dental licensure in Canada. As of January 1997, graduates of dental programs accredited by the American Dental Association's Commission on Dental Accreditation (ADA Commission) must complete successfully the same examinations as graduates of programs accredited by the Commission on Dental Accreditation of Canada (CDAC) to be licensed to practice in Canada. In addition, NDEB's examination system for graduates of dental programs that are not accredited by CDAC or the ADA Commission (i.e. international programs) will be discontinued on December 31, 1999. As of January 1, 2000, graduates of non-accredited programs will be required to complete a CDAC accredited, university-based qualifying program to be eligible to participate in the same certification process as graduates of ADA Commission and CDAC accredited dental programs.

Accreditation↗
PubMed1997

Recombinant human interleukin-11 directly promotes megakaryocytopoiesis in vitro.

We have investigated the mechanism of action of the thrombopoietic cytokine, recombinant human interleukin-11 (rhIL-11), on megakaryocytopoiesis in vitro. We have shown that rhIL-11-induced murine and human megakaryocytopoiesis are not mediated by thrombopoietin (Tpo). Murine megakaryocytes (MKs) were produced from bone marrow (BM) mononuclear cells cultured with rhIL-11, IL-3, and a combination of the two cytokines. Conditioned media (CM) were collected and assayed for the presence of biologically active Tpo. Tpo activity was not detected in any of the CMs tested. Next, human BM CD34+ cells were cultured in serum-free fibrin clot medium with rhIL-11, IL-3, or rhIL-11 plus IL-3 and an antibody that neutralizes human Tpo activity. No inhibition of either burst-forming unit-MK- or colony-forming unit-MK-derived colony formation was observed. The antibody did partially inhibit steel factor-induced MK-colony formation, suggesting that the actions of this cytokine are mediated, in part, by Tpo. We determined that MKs can be direct targets of rhIL-11 by showing the expression of functional IL-11 receptor on these cells. Total RNA was prepared from cultured human BM CD41+CD14- cells (MKs) and IL-11 receptor alpha chain mRNA was detected in the MKs by reverse transcription-polymerase chain reaction. Analysis of single-sorted CD41+CD14- cells confirmed that the observed IL-11 receptor expression was not due to contaminating CD41- cells in the pool. The presence of rhIL-11 receptor alpha chain protein in the cells was established by Western blot analysis. After a short exposure of purified BM MKs to rhIL-11, enhanced phosphorylation of both its signal transduction subunit, gp130, and the transcription factor, STAT3 was detected, showing a direct activation of receptor signaling by the cytokine. Consistent with the lack of effect of rhIL-11 on platelets in vivo, IL-11 receptor alpha chain mRNA and protein were not detected in isolated human platelets. These data indicate that rhIL-11 acts directly on MKs and MK progenitors but not on platelets.

Animals↗
PubMed1997

The biphasic opening of the blood-brain barrier in the cortex and hippocampus after traumatic brain injury in rats.

This study examined the time course of the blood-brain barrier (BBB) opening and correlated this with brain edema formation after a lateral controlled cortical impact (CCI) brain injury in rats. Quantitative measurement of Evans blue (EB) extravasation using fluorescence was employed at 2, 4, 6 h and 1, 2, 3, 4 and 7 days after injury. Brain edema was measured by specific gravity of the tissue at corresponding time points. Two prominent EB extravasations were observed at 4-6 h and 3-day after injury in the injury-site cortex and the ipsilateral hippocampus. Brain edema became progressively more severe over time and peaked at 24 h after injury and began to decline after day 3. These results suggest that there is a biphasic opening of the BBB after CCI brain injury and the second opening of the BBB does not contribute to a further increase in edema formation.

Animals↗
PubMed1997

Regional brain polyamine levels in permanent focal cerebral ischemia.

Transient global cerebral ischemia has been shown to induce marked changes in the polyamine pathway with a significant increase in putrescine, the product of the ornithine decarboxylase reaction. This study examined the relationship between tissue and extracellular polyamines and regional cerebral blood flow and brain edema. Six hours of focal ischemia in cats (n = 10) was produced by permanent middle cerebral artery occlusion. Extracellular polyamines were measured in extracellular fluid obtained by microdialysis. Regional cerebral blood flow using laser Doppler flowmetry and specific gravity, an indicator of brain edema, were measured in contralateral (non-ischemic), penumbra and densely ischemic brain regions. A significant increase in the tissue putrescine level was found in the penumbra but there was no difference in the putrescine levels between contralateral and densely ischemic regions. There was no significant change in the spermidine and spermine levels in the three regions. Extracellular levels of putrescine and spermidine were found to be significantly lower than the tissue levels and no change in polyamines was observed in any region. Significant edema formation was observed in densely ischemic and penumbra regions. This is the first demonstration that tissue putrescine is increased in the penumbra region, an area of incomplete ischemia that is developing brain edema.

Animals↗
PubMed1997

Birth-date dependent population ethics: critical-level principles.

"This paper investigates birth-date dependent principles for social evaluation in an intertemporal framework in which population size may vary. We weaken the strong Pareto principle in order to allow individuals' birth dates to matter in establishing a social ordering. Using the axiom independence of the utilities of the dead, we characterize population principles with a recursive structure. If the individual substitution principle and an individual intertemporal equivalence axiom are added, birth-date dependent generalizations of the critical-level generalized utilitarian principles result. Stationarity leads to the special case of geometric discounting."

Delivery, Obstetric↗
PubMed1997

Affect regulation and suicide attempts in adolescent inpatients.

OBJECTIVE: To examine the relationship between affect dysregulation and self-destructive behaviors in adolescent suicide attempters. METHOD: Measures of affect dysregulation, number of risk-taking behaviors in past year, presence of self-mutilative behaviors in past year, and number of different types of self-mutilative behaviors in past year were individually administered to adolescents admitted to an inpatient unit who were either suicide ideators (n = 25) or suicide attempters (n = 35). RESULTS: Suicide attempters reported significantly higher levels of affect dysregulation and a greater number of different types of self-mutilative behaviors in the past year than suicide ideators. In addition, the number of different types of self-mutilative behaviors in the past year had the strongest relationship to suicide attempts. CONCLUSION: Suicidal behavior among adolescent psychiatric patients is related to poor affect regulation. A risk factor for suicidal behavior in adolescents is a broad range of self-mutilative acts in the year preceding the suicide attempt.

Adolescent↗
PubMed1997

Protective effects of ifenprodil on ischemic injury size, blood-brain barrier breakdown, and edema formation in focal cerebral ischemia.

OBJECTIVE: Ifenprodil, a polyamine site N-methyl-D-aspartate receptor/channel antagonist, has been reported to decrease infarction volume after cerebral ischemia. However, the possible mechanisms of this protective effect have not been studied in detail. We investigated the effects of ifenprodil on ischemic injury size, blood-brain barrier (BBB) permeability, regional brain edema, and cerebral blood flow. METHODS: Focal ischemia for 6 hours was produced by permanent occlusion of the middle cerebral artery in 15 anesthetized cats. Treatment with drug (n = 8) or vehicle (n = 7) was initiated at 5 minutes after ischemia and continued for 3 hours. Physiological variables were continuously monitored during experiments. We measured ischemic injury size, brain edema, and BBB permeability to Evans blue and determined regional cerebral blood flow by using laser doppler flowmetry. RESULTS: Both ischemic injury size and BBB permeability were smaller in the ifenprodil-treated group, compared with the saline-treated group (P < 0.05). Ifenprodil treatment also attenuated brain edema formation in the dense ischemic region, compared with saline treatment (1.035 +/- 0.002 versus 1.028 +/- 0.002, P < 0.05). There was no significant change in cerebral blood flow with ifenprodil treatment. CONCLUSION: Findings from this study confirm that ifenprodil treatment results in a significant decrease in the size of ischemic injury after focal ischemia. The tissue-sparing effect of ifenprodil is not related to its vasoactive properties. It is likely that its neuroprotective effects are related to its ability to antagonize N-methyl-D-aspartate receptors, which results in a decrease in brain edema and BBB permeability.

Animals↗
PubMed1997

Lessons to be learned: a case study approach. Hyperactivity and confusion in the presentation of hyoscine overdose.

The case report is presented of a ten-and-a-half year old boy with acute onset of confusion and visual hallucinations, subsequently confirmed to be due to hyoscine toxicity following ingestion of over-the-counter (OTC) travel sickness tablets. It is suggested that packs of such pills should carry a prominent cautionary label. A clear clinical history is very important--not only in aiding the differentiation of acute viral infections involving the central nervous system (such as acute encephalitis) from drug toxicity, but also in rationalizing any further diagnostic investigations. The possible underlying reasons for drug ingestion in this case are discussed.

Antiemetics↗
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↗