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Biomedical subjects

D Malcolm

Publications and source records attributed to D Malcolm.

At least 19 recordsLinked to original sources
PubMed2005

Drug use in English professional football.

OBJECTIVES: To examine several issues related to drug use in English professional football. More particularly the project sought to gather data on: players' use of permitted supplements (mineral and vitamin pills and creatine); whether they sought advice, and if so from whom, about their use of supplements; their experience of and attitudes towards drug testing; their views on the extent of the use of banned performance enhancing and recreational drugs in football; and their personal knowledge of players who used such drugs. METHODS: With the cooperation of the Professional Footballers Association (PFA), reply paid postal questionnaires were delivered to the home addresses of all 2863 members of the PFA. A total of 706 questionnaires were returned, a response rate of just under 25%. RESULTS: Many players use supplements, although almost one in five players does so without seeking qualified professional advice from anyone within the club. Blood tests are rarely used to monitor the health of players. One third of players had not been tested for drugs within the preceding two years, and 60% felt that they were unlikely to be tested in the next year. The use of performance enhancing drugs appears to be rare, although recreational drugs are commonly used by professional footballers: 6% of respondents indicated that they personally knew players who used performance enhancing drugs, and 45% of players knew players who used recreational drugs. CONCLUSIONS: There is a need to ensure that footballers are given appropriate advice about the use of supplements in order to minimise the risk of using supplements that may be contaminated with banned substances. Footballers are tested for drugs less often than many other elite athletes. This needs to be addressed. The relatively high level of recreational drug use is not reflected in the number of positive tests. This suggests that many players who use recreational drugs avoid detection. It also raises doubts about the ability of the drug testing programme to detect the use of performance enhancing drugs.

Adolescent↗
PubMed1997

Cellular responses to surgical trauma, hemorrhage, and resuscitation with diaspirin cross-linked hemoglobin in rats.

BACKGROUND: Resuscitation with acellular oxygen carrier solutions offers the potential advantage of improved oxygen delivery compared with crystalloid solutions, but the detailed consequences of improved resuscitation have not been fully evaluated. This study evaluated local and systemic cellular effects of trauma, hemorrhage, and resuscitation in a model of hemorrhage and surgical trauma. METHODS: Rats with a 10 cm full-thickness incisional wound and a 15 mL/kg hemorrhage were either not resuscitated or resuscitated with blood or diaspirin cross-linked hemoglobin (DCLHb). Cellular proliferative responses were evaluated at 1.5, 6, 24, and 48 hours after wounding by labeling in vivo with 5-bromo-2'-deoxyuridine. Plasma levels of interleukin-6, tumor necrosis factor-alpha, and interferon-gamma were measured by bioassay or enzyme-linked immunosorbent assay (ELISA). Bacterial translocation was measured by culturing liver homogenates. RESULTS: Trauma inhibited keratinocyte and hepatocyte proliferation at 1.5 and 6 hours, and stimulated subsequent proliferation of keratinocytes and liver nonparenchymal cells. DCLHb stimulated wound keratinocyte proliferation, attenuated the inhibition of hepatocyte proliferation, eliminated bacterial translocation to the liver, protected the intestine from ischemic damage, and induced a rapid increase of interleukin-6 during the early phase of injury. CONCLUSIONS: Surgical trauma alone, or in combination with hemorrhage, modulated cell proliferation both in the wound and in the remote organs of intestine and liver. DCLHb enhanced wound healing and cell proliferation as well as, or better than, freshly drawn blood, which may be beneficial for trauma care.

Animals↗
PubMed1996

Fluid resuscitation in a model of uncontrolled hemorrhage: too much too early, or too little too late?

UNLABELLED: Early fluid resuscitation in hypotensive trauma patients is controversial due to the risk of increasing blood loss and mortality. We determined the effects of infusion rate and time of resuscitation on blood loss and mortality and compared the outcome to nonresuscitated animals in severe, uncontrolled hemorrhagic shock in a rat model. In anesthetized rats, piercing of the infrarenal aorta with a 25-G needle caused a fall of mean arterial pressure to <20 mm Hg and blood loss of about 20 ml/kg in 90% of the animals. Animals were assigned to the following treatment groups (n = 6): 60 ml/kg of lactated Ringer's solution (LR) infused at a rate of 1.5 ml/min and given at 2.5 min (Group I), 5 min (Group II), or 10 min (Group III) postinjury, or LR infused at a rate of 3.0 ml/min and given at 5 min (Group IV) or 10 min (Group V) postinjury. Another group (n = 9) was not resuscitated. The animals were followed for 3 hr. Total blood loss in Group I (30.5 +/- 2.6 ml/kg) was significantly (P < 0.05) higher when compared to nonresuscitated animals (22.1 +/- 0.8 ml/ kg) or Group III (22.7 +/- 1.0 ml/kg), and also significantly higher in Group IV (35.8 +/- 4.1 ml/kg) when compared to nonresuscitated animals or Group V (23.0 +/- 1.2 ml/kg). The mortality rate was 7/9 in nonresuscitated animals and 5/6 in Group IV, both were significantly higher than in Groups II, III, and V (0 or 1/6) and markedly higher than in Group I (2/6). CONCLUSIONS: In this model of uncontrolled hemorrhage, initially uncorrected severe shock resulted in a high mortality rate. The risk of increased blood loss and mortality associated with early fluid resuscitation could be diminished by avoiding too fast of infusion rates early after the injury.

Animals↗
PubMed1996

Early resuscitation with low-volume PolyDCLHb is effective in the treatment of shock induced by penetrating vascular injury.

OBJECTIVE: To study the efficacy of an oxygen-carrying solution in early resuscitation of hemorrhagic shock induced by penetrating vascular injury. DESIGN: Experimental study with anesthetized rats. MATERIALS AND METHODS: Severe hemorrhagic shock was induced by a 25-gauge needle puncture to the infrarenal aorta. Forty animals were resuscitated 10 minutes after injury with either lactated Ringer's solution (LR; 60 mL/kg), 7.5% hypertonic saline (HTS; 5 mL/kg), or modified diaspirin cross-linked hemoglobin (PolyDCLHb; 5 or 20 mL/kg) or were not resuscitated (NR) and followed for 6 hours. RESULTS: Total blood loss was similar in all treatment groups. Mean arterial pressure was restored to baseline values, base deficit was corrected to base excess, and venous oxygen saturation improved with PolyDCLHb and more slowly with LR but persisted below baseline values with HTS and NR. The 6-hour mortality rates were zero of eight (low-dose PolyDCLHb), three of eight (high-dose PolyDCLHb), two of eight (LR), six of eight (HTS), and six of eight (NR). CONCLUSION: Early resuscitation with low-volume hemoglobin is effective in restoring tissue perfusion and improving survival in uncontrolled hemorrhagic shock.

Animals↗
PubMed1996

Subcutaneous tissue oxygen pressure: a reliable index of peripheral perfusion in humans after injury.

The usual initial life-threatening effect of injury is hypovolemic shock. In the hierarchical physiologic response to hypovolemia, perfusion of peripheral tissues is sacrificed early and restored late. But the usual hemodynamic and metabolic measurements of blood pressure, urine output, and base deficit are not reliable indices of peripheral perfusion. Although the Clark electrode can quantitate tissue oxygen pressure and thereby serve as an index of perfusion, its use is compromised by several technical deficiencies. Recently, an optical method (optode) using fluorescent technology has been developed for measurement of oxygen tension in subcutaneous tissue (P sgO2). Our studies compared this device with the Clark electrode in the laboratory and tested its value in both animal and clinical studies of hypovolemic shock. The results of these several studies demonstrated that: (1) the new oximeter tracked a rapid fall or rapid rise of oxygen tension between room air (150 mm Hg) and 0 mm Hg ( a glucose oxidase/catalase solution) as well as the Clark electrode without encountering its technical problems; (2) with an acute hemorrhage to 20% of base line, the PsgO2 was found to decline rapidly in parallel with the decline of mean arterial pressure (MAP). Although the MAP rapidly returned to normal after immediate complete return of all shed blood, the PsgO2 did not reach normal levels for at least 2 hours, suggesting persistent peripheral vasoconstriction. (3) Studies in progress suggest that between 35 and 78% of trauma patients (n = 18) adequately resuscitated for hypovolemia b customary criteria have a decreased level of PsgO2 for as long as 60 hours after resuscitation for injury. If care is taken to prevent other causes of catecholamine induced vasoconstriction such as pain, fear, cold, and arterial hypoxia, these several results suggest that a certain number of injured patients are inadequately resuscitated despite the return to normal of conventional hemodynamic measurements. The serial analysis of PsgO2 may assist in managing patients and promote better understanding of the responses to injury.

Animals↗
PubMed1994

Diaspirin crosslinked hemoglobin (DCLHb): control of pressor effect with anti-hypertensive agents.

Diaspirin crosslinked hemoglobin (DCLHb) administration elevates mean arterial pressure (MAP). The purpose of this study was to determine whether commonly used antihypertensive agents could control this pressor effect in rats. Awake rats were injected intravenously (i.v.) with 280 mg/kg of DCLHb. Fifteen minutes later when MAP was 25-30% above baseline and heart rate (HR) was reciprocally decreased, prazosin (2 mg/kg;an alpha adrenergic blocker), nitroglycerine (NTG; 10-150 mcg/min; a nitrovasodilator), nicardipine (0.204-0.08 mg/hr; a calcium channel blocker) or labetalol (5 mg/kg; an alpha/beta adrenergic blocker) was administered i.v. All four classes of antihypertensive agents promptly restored MAP to baseline. Coincident with the return of MAP to baseline, HR was restored to baseline in prazosin and NTG treated animals, however, bradycardia persisted in those animals treated with nicardipine and labetalol, most likely due to the negative chronotropic properties of these agents. We conclude that the pressor effect of DCLHb can be readily controlled with at least four different classes of commonly used antihypertensive agents.

Animals↗
PubMed1992

Diaspirin cross-linked hemoglobin solution as a resuscitative fluid following severe hemorrhage in the rat.

The effect of diaspirin cross-linked hemoglobin (DCLHb) on mean arterial pressure (MAP) and heart rate (HR) was compared to Ringer's lactate (RL) and shed blood in a 70% lethal model of hemorrhage (35 cc/kg blood loss) in conscious rats. All animals resuscitated with DCLHb regardless of dose (17.5 and 35 cc/kg) and concentration (7% and 10% solution) exhibited complete restoration of MAP and HR which was maintained for at least 5 hrs. Hemodynamic responses in DCLHb-treated animals were not significantly different from 35 cc/kg blood-treated animals. In RL (105 cc/kg) treated animals the MAP was restored to 60-70% of baseline. 24 hr survival in animals resuscitated with fluids ranged between 88-100% and was not significantly different between treatment groups.

Animals↗
PubMed1992

Dissociation between prostaglandin levels and blood flow to the retina and choroid in the newborn pig after nonsteroidal antiinflammatory drugs.

To assess whether prostaglandins contribute to the control of basal retinal and choroidal hemodynamics, retinal (RBF) and choroidal blood flow (ChBF) were measured by a microsphere technique in 1- to 4-day-old pigs before and after (at 20 and 60 min) administration of indomethacin (0.3 mg/kg, n = 6 or 10 mg/kg, n = 5), ibuprofen (40 mg/kg, n = 7), naproxen (20 mg/kg, n = 5) or vehicle (n = 8). In 40 other animals, PGF2 alpha, PGE2, and 6-keto-PGF1 alpha were measured in the retina and choroid at times corresponding to blood flow measurements. Mean arterial blood pressure and blood gases and pH were not altered by any of the agents. Except for the lower dose of indomethacin (0.3 mg/kg), which did not change retinal and choroidal prostaglandin concentrations, the prostaglandin levels were decreased similarly (P < 0.01) by the three drugs. However, RBF and ChBF were not changed by ibuprofen and naproxen, but decreased to the same extent after low and high doses of indomethacin. The data suggest that the effects of indomethacin on RBF and ChBF cannot be simply attributed to prostaglandin synthesis inhibition, and that prostaglandins may not play a significant role in controlling basal blood flow to the retina and choroid.

Animals↗
PubMed1988

Endotoxin-induced hypocalcemia results in defective calcium mobilization in rats.

Hypocalcemia is common in critically ill patients with sepsis; however, its etiology remains unclear. We have previously reported that hypocalcemia occurs in approximately 20% of patients with gram-negative septicemia. Based upon this finding, we evaluated the effect of endotoxin on calcium homeostasis in laboratory animals. We report here that endotoxin produces a dose-related decrease in circulating ionized calcium levels and impairs calcium mobilization during ethylenebis (oxyethylenenitrilo)-tetraacetic acid infusion. We conclude that endotoxin or its products can cause ionized hypocalcemia during sepsis by impairing calcium mobilization.

Animals↗
PubMed1988

Hypercalcemia attenuates blood pressure response to epinephrine.

The potent alpha and beta adrenergic actions of epinephrine are probably mediated through an increase in free intracellular calcium concentration. Despite an absence of experimental evidence, many clinicians administer epinephrine with calcium to augment its cardiovascular effects. We evaluated the effects of calcium on epinephrine's pressor response in both normal and endotoxin-treated rats by administering epinephrine to animals made hypercalcemic with calcium chloride or hypocalcemic with the calcium chelator EGTA. EPI, given in incremental doses of 10, 20 and 50 micrograms/kg, produced incremental increases in mean arterial pressure. Calcium chloride infused i.v. at a rate of 50 mg/ml/hr significantly (P less than .05) blunted (50% decrease) the hypertensive response to 50 micrograms/kg epinephrine in normal animals. In endotoxin-treated rats, calcium chloride at 50 mg/ml/hr significantly blunted the hypertensive response to 10 micrograms/kg (73% decrease), 20 micrograms/kg (62% decrease) and 50 micrograms/kg (50% decrease) epinephrine. Endotoxemia plus calcium chloride at 25 mg/ml/hr also significantly blunted (30% decrease) the hypertensive response to 50 micrograms/kg EPI. By contrast, hypocalcemia produced by EGTA (30 mg/ml/hr) had no effect on epinephrine's hypertensive effects in normal or endotoxemic rats. Since calcium chloride significantly diminishes epinephrine's hypertensive effects in both normal and endotoxin-treated rats, the clinical use of calcium chloride along with epinephrine may not have a sound experimental basis.

Animals↗
PubMed1987

Verapamil reverses calcium cardiotoxicity.

High circulating concentrations of calcium are toxic to the heart and may cause cardiac arrhythmias and arrest. To investigate the therapeutic use of calcium antagonists in hypercalcemia, we evaluated the efficacy of verapamil hydrochloride and magnesium chloride in the treatment of experimental calcium-induced cardiac arrest in laboratory rats. Verapamil rapidly reversed the experimental calcium-induced arrest and improved survival (83% survival versus 0% in controls). Magnesium failed to reverse this toxic event. We conclude from these experimental studies that verapamil may be useful in the treatment of hypercalcemic cardiac toxicity.

Animals↗
PubMed1987

Glucagon's chronotropic action is calcium dependent.

Evidence is increasing that many anesthetics and cardiovascular agents alter cellular Ca kinetics and flux. In prior work we demonstrated that the tachycardic effects of glucagon were significantly blunted by Ca channel blockade, but not by beta adrenergic receptor blockade. Thus, the chronotropic effects of glucagon may be dependent upon extracellular Ca levels. Based upon these observations, we tested the hypothesis that changes in circulating ionized Ca concentrations may alter glucagon's ability to increase heart rate in rats. In conscious normocalcemic rats, glucagon's tachycardic actions were dose related with peak effects obtained at 1 to 2 min and persisting approximately 10 min after 1.0 mg/kg of glucagon. The effects of altered Ca levels on glucagon tachycardia were evaluated in three groups of rats: 1) rats rendered hypercalcemic by the infusion of Ca chloride (10, 50 or 100 mg/ml/hr); 2) rats rendered hypocalcemic by infusion of the Ca chelator EDTA (15 or 30 mg/ml/hr); and 3) normocalcemic rats infused with saline. Normocalcemic rats had a mean ionized Ca level of 4.73 mg/dl. In rats, increasing Ca chloride doses resulted in increasing mean serum ionized Ca levels (5.24, 8.35 and 15.2 mg/dl, respectively), whereas increasing doses of EDTA produced progressive decreases in mean ionized Ca (3.62 and 2.13 mg/dl, respectively). Severe hypo (2.13 mg/dl)- or hypercalcemia (15.2 mg/dl) significantly blunted glucagon's chronotropic action (51 and 44%, respectively). From these data, we conclude that glucagon has its maximal tachycardic action at physiologic Ca levels (being blunted by both hyper- and hypocalcemia), indicating that this effect of glucagon is Ca dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1986

Glucagon is an antagonist of morphine bradycardia and antinociception.

Glucagon and its receptors have been identified within the mammalian brain, and their anatomical distribution correlates well with the distribution of opioid peptides and their receptors. To evaluate possible physiological interactions between these two peptidergic systems, we examined the effects of glucagon on two opioid responses - bradycardia and antinociception. Glucagon administered either intravenously (iv) (100-1000 micrograms/kg) or intracerebroventricularly (icv) (5 micrograms) significantly attenuated morphine-induced (200 micrograms/kg, iv) bradycardia without producing any alterations in cardiovascular parameters when given alone. Furthermore, glucagon did not antagonize the bradycardia produced by phenyldiguanide (10 micrograms/kg, iv), a non-opioid substance. Peripheral (1 mg/kg, iv) and central (5 micrograms, icv) glucagon pretreatment antagonized morphine-induced (7.5 mg/kg, intraperitoneal) antinociception by 67% and 86%, respectively, at 30 minutes (as determined by the hot plate test). Glucagon treatment alone at these doses did not alter baseline response latencies. In both cases, central injections of glucagon were more effective than iv injections in antagonizing morphine's effects. These findings demonstrate a central action for glucagon and provide the first evidence that this neuropeptide may function as an endogenous antagonist of opioid actions.

Analgesia↗