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PubMed1972

Vampire bat control by systemic treatment of livestock with an anticoagulant.

The blood of beef cattle given single doses (1 milligram per kilogram of body weight) of diphenadione (2-diphenylacetyl-1,3-indandione) became toxic to vampire bats (Desmodus rotundus) and remained toxic for 3 days without harming the cattle. Cattle at three ranches in Mexico treated with single intraruminal injections of diphenadione experienced a reduction in vampire bat bites of 93 percent. Bioassays of milk and liver from cattle treated orally with diphenadione in the laboratory indicated that there were no residue problems.

Administration, Oral↗
PubMed2006

Ethical and equity issues in lung transplantation and lung volume reduction surgery.

New medical and scientific disciplines are often developed in haste with rampant enthusiasm and scant regard for the balance between action and thoughtful deliberation. Driven by the desire to prolong life and provide a better quality of life for desperately sick individuals, the twin modalities of lung transplantation and lung volume reduction therapy have only just reached their majority. Both are invested with the capacity to help and to harm so it is right to consider carefully their ethical and equitable distribution. Much has been learned in the last 20 years to assist in these deliberations. First, how can we ensure equity of access to transplant services and equality of outcomes? How do we balance resource allocation of a precious and scarce resource with individual recipient needs? Does the concept of distributive justice prevail in our daily work in this field? How do we honour the donor and their family? How do we as practitioners avoid ethical dilemmas related to personal bias and justifiable reward for services rendered? Finally, how do we learn to incorporate ethical forethought and planning guided by experts in the area into everyday behaviour?

Conflict of Interest↗
PubMed2006

Beneficial biofilm formation by industrial bacteria Bacillus subtilis and related species.

Biofilms are densely packed multicellular communities of microorganisms attached to a surface or interface. Bacteria seem to initiate biofilm formation in response to specific environmental cues, such as nutrient and oxygen availability. Biofilms undergo dynamic changes during their transition from free-living organisms to sessile biofilm cells, including the specific production of secondary metabolites and a significant increase in the resistivity to biological, chemical, and physical assaults. Bacillus subtilis is an industrially important bacterium exhibiting developmental stages. It forms rough biofilms at the air-liquid interface rather than on the surface of a solid phase in a liquid, due to the aerotaxis of the cells. Biofilm formation by B. subtilis and related species permits the control of infection caused by plant pathogens, the reduction of mild steel corrosion, and the exploration of novel compounds. Although it is obviously important to control harmful biofilm formation, the exploitation of beneficial biofilms formed by such industrial bacteria may lead to a new biotechnology.

Bacillus subtilis↗
PubMed2003

Female genital cutting: a harmless practice?

A recent article in Medical Anthropology Quarterly (Obermeyer 1999) argues that the "facts" about the "harmful effects" of female genital cutting (FGC) are "not sufficiently supported by the evidence" (p. 79). The article suggests three further hypotheses, among others: (1) FGC may be of minimal harm because the more educated continue the practice just as much as the less educated; (2) FGC may be of minimal harm because it is so widespread and persistent; (3) FGC may be of minimal harm because the supposed link between the clitoris and female sexual pleasure is a social construction rather than a physiological reality. I challenge these hypotheses. I say that by appropriate standards of evaluation, FGC is harmful. Finally, I submit that most FGC is a proper matter of concern because it is the irreversible reduction of a human capacity in the absence of meaningful consent.

Africa↗
PubMed2001

A bibliographical survey of bruxism with special emphasis on non-traditional treatment modalities.

After proposing a common-sense definition of bruxism, this partial review distills its various symptoms and consequences from the literature. That literature suggests that the splint-the most popular treatment modality-falls short in some respects. The research literature is even less sanguine about the efficacy of such other traditional therapies as sound alarms and stress reduction. Given the limited success of traditional approaches, and given, moreover, the high incidence of bruxism and its harmful consequences, clinicians may occasionally be interested in experimenting with non-intrusive, safe, less widely known, treatment modalities. To meet this need, this review-unlike all other reviews of the subject-focuses on such comparatively unpopular or recent approaches.

Bruxism↗
PubMed1999

Lifestyle modifications to prevent and control hypertension. 5. Recommendations on dietary salt. Canadian Hypertension Society, Canadian Coalition for High Blood Pressure Prevention and Control, Laboratory Centre for Disease Control at Health Canada, Heart and Stroke Foundation of Canada.

OBJECTIVE: To provide updated, evidence-based recommendations concerning the effects of dietary salt intake on the prevention and control of hypertension in adults (except pregnant women). The guidelines are intended for use in clinical practice and public education campaigns. OPTIONS: Restriction of dietary salt intake may be an alternative to antihypertensive medications or may supplement such medications. Other options include other nonpharmacologic treatments for hypertension and no treatment. OUTCOMES: The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered. EVIDENCE: A MEDLINE search was conducted for the period 1966-1996 using the terms hypertension, blood pressure, vascular resistance, sodium chloride, sodium, diet, sodium or sodium chloride dietary, sodium restricted/reducing diet, clinical trials, controlled clinical trial, randomized controlled trial and random allocation. Both trials and review articles were obtained, and other relevant evidence was obtained from the reference lists of the articles identified, from the personal files of the authors and through contacts with experts. The articles were reviewed, classified according to study design and graded according to level of evidence. In addition, a systematic review of all published randomized controlled trials relating to dietary salt intake and hypertension was conducted. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by untreated hypertension. BENEFITS, HARMS AND COSTS: For normotensive people, a marked change in sodium intake is required to achieve a modest reduction in blood pressure (there is a decrease of 1 mm Hg in systolic blood pressure for every 100 mmol decrease in daily sodium intake). For hypertensive patients, the effects of dietary salt restriction are most pronounced if age is greater than 44 years. A decrease of 6.3 mm Hg in systolic blood pressure and 2.2 mm Hg in diastolic blood pressure per 100 mmol decrease in daily sodium intake was observed in people of this age group. For hypertensive patients 44 years of age and younger, the decreases were 2.4 mm Hg for systolic blood pressure and negligible for diastolic blood pressure. A diet in which salt is moderately restricted appears not to be associated with health risks. RECOMMENDATIONS: (1) Restriction of salt intake for the normotensive population is not recommended at present, because of insufficient evidence demonstrating that this would lead to a reduced incidence of hypertension. (2) To avoid excessive intake of salt, people should be counselled to choose foods low in salt (e.g., fresh fruits and vegetables), to avoid foods high in salt (e.g., pre-prepared foods), to refrain from adding salt at the table and minimize the amount of salt used in cooking, and to increase awareness of the salt content of food choices in restaurants. (3) For hypertensive patients, particularly those over the age of 44 years, it is recommended that the intake of dietary sodium be moderately restricted, to a target range of 90-130 mmol per day (which corresponds to 3-7 g of salt per day). (4) The salt consumption of hypertensive patients should be determined by interview. VALIDATION: These recommendations were reviewed by all of the sponsoring organizations and by participants in a satellite symposium of the fourth International Conference on Preventive Cardiology. They have not been clinically tested. SPONSORS: The Canadian Hypertension Society, the Canadian Coalition for High Blood Pressure Prevention and Control, the Laboratory Centre for Disease Control at Health Canada, and the Heart and Stroke Foundation of Canada.

Adult↗
PubMedDate not supplied

The unbearable lightness of "light" cigarettes: a comparison of smoke yields in six varieties of Canadian "light" cigarettes.

BACKGROUND: Labelling cigarettes as "light" or "mild" is claimed to be one of the biggest marketing scams in Canadian history. Arguably, such labelling implies that these varieties of cigarettes are less harmful than "regular" cigarettes. In Canada, a food product can be labelled "light" if there is a 25% reduction from the "reference food" and if the constituent being reduced is clearly identified (e.g., light in fat). Cigarette labelling does not comply with these regulations, however. To examine whether or not some tobacco constituents meet the 25% reduction criterion, we compared yields of 41 toxic and/or carcinogenic smoke constituents in six varieties of "light" cigarettes to the yields of "regular" cigarettes. We selected cigarettes from the two most popular Canadian brands, Du Maurier and Players. METHODS: Using a set of data provided by Imperial Tobacco Canada and made available to the public by the Government of British Columbia, we compared yields measured under a laboratory protocol (modified ISO) that was designed to provide a more rigorous evaluation of the differences between varieties of cigarettes and a more accurate assessment of smokers' potential smoke intake than the traditional protocol (standard ISO). FINDINGS: For all six varieties of "light" cigarettes, the yields of nicotine were higher by an average of 5% (range: 1% to 13%). The 25% reduction criterion was not met for any variety of "light" cigarettes concerning yields of tar. For all cigarettes tested, yields of tar were reduced on average by only 16% (range: 5% to 22%). For carbon monoxide (CO), only Player's Smooth Light had an over 25% reduction (30%) compared with Player's Regular. Conversely, yield of CO was 24% higher for Du Maurier Lights compared with Du Maurier Regular. As for the other smoke constituents, the majority (75%) were not reduced by 25% or more in "light" cigarettes, and a sizeable proportion of yields (e.g., acrylonitrile, benzene, chromium, m+p cresol, mercury, nickel, toluene) were larger in these varieties of cigarettes. Only yields of formaldehyde, crotonaldehyde, 1-aminonaphtalene, and proprionaldehyde were systematically reduced in all varieties of "light" cigarettes. CONCLUSION: The six varieties of "light" cigarettes examined in this study do not differ substantially from "regular" cigarettes in terms of smoke yields. We argue that the modified ISO protocol should be implemented for a more valid comparison of potential smoke yields in all varieties of cigarettes and that labelling based on this protocol should be promoted.

Advertising↗
PubMed1994

Effect of continuous combined estrogen and desogestrel hormone replacement therapy on serum lipids and lipoproteins.

OBJECTIVE: To determine the effects of continuous combined hormone replacement therapy with desogestrel and 17 beta-estradiol (E2) on serum lipids and lipoproteins. METHODS: Fifty-seven healthy postmenopausal women of less than 60 years of age were studied prospectively and treated with oral desogestrel 0.15 mg/day and micronized 17 beta-E2 1 mg/day, both taken continuously. Fasting venous blood samples for serum lipids and lipoproteins were taken before and after 6 and 12 months of treatment. RESULTS: Thirty-two women completed the study. Levels of all serum lipids and lipoproteins fell significantly by 6 months and remained low at 12 months. The mean percentage reduction after 12 months of treatment was 12.8% for high-density lipoprotein (HDL) cholesterol, which largely resulted from a reduction in the HDL2 subfraction, which fell by 25.7%. The mean percentage reduction for both low-density lipoprotein (LDL) cholesterol and triglycerides was 7.7%. The median percentage reduction for lipoprotein (a) was 17.6%. CONCLUSIONS: This combination of hormone replacement therapy had profound effects on serum lipids and lipoproteins. According to current concepts, reductions in total and LDL cholesterol, triglycerides, and lipoprotein (a) may reduce cardiovascular disease risk. The reduction in HDL was unexpected, given the rise in HDL that has been demonstrated when desogestrel is combined with ethinyl estradiol in the contraceptive pill. The lowering of HDL observed in this study is undesirable and may be potentially harmful. Our results indicate that when desogestrel 0.15 mg/day is combined with micronized 17 beta-E2 1 mg/day in a continuous manner, the effects of the progestogen on HDL predominate and cause a reduction in HDL and the HDL2 subfraction.

Cholesterol, HDL↗
PubMed2002

Removal of toxic metals from leachates from hazardous solid wastes and reduction of toxicity to microtox by the use of calcium alginate beads containing humic acid.

Improper disposal of hazardous wastes can lead to release of potentially harmful substances through leaching such as heavy metals, which ultimately contaminate soil, sediment surface water, and groundwater through runoff. To remove these toxic metals and avoid any adverse effect on the ecosystem, a novel approach involving calcium alginate (CA) beads containing humic acid (HA) was used. For this, 10% leachates of the waste obtained from two major industrial units with electroplating processess were prepared at neutral pH and analyzed by atomic absorption spectrophotometry (AAS). Both leachates contained Cd, Cu, Cr, Ni, Mn, Fe, and Zn. The concentrations of Ni, Mn, Fe, and Zn in the waste were found to be significant. The leachates analyzed were passed through columns packed with calcium alginate beads with or without humic acid. The concentrations of various metals in beads and in different fractions collected after adsorption were measured. Data recorded indicate that calcium alginate beads containing humic acids are more efficient in removal of all metals in substantial amounts from the two leachates. Along with removal of metals, this process led to considerable detoxification of the leachates as tested by Microtox assay, indicated by earlier protection and higher EC(50). The significance of the results in relation to removal of toxic metals by beads containing humic acid is discussed.

Adsorption↗
PubMed2006

Effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST segment elevation acute coronary syndromes: benefit and harm in different age subgroups.

OBJECTIVE: To investigate whether the beneficial and harmful effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST elevation acute coronary syndromes (NSTE-ACS) depend on age. METHODS: A meta-analysis of six trials of platelet glycoprotein IIb/IIIa receptor blockers in patients with NSTE-ACS (PRISM, PRISM-PLUS, PARAGON-A, PURSUIT, PARAGON-B, GUSTO IV-ACS; n = 31 402) was performed. We applied multivariable logistic regression analyses to evaluate the drug effects on death or non-fatal myocardial infarction at 30 days, and on major bleeding, by age subgroups (<60, 60-69, 70-79, > or =80 years). We quantified the reduction of death or myocardial infarction as the number needed to treat (NNT), and the increase of major bleeding as the number needed to harm (NNH). RESULTS: Subgroups had 11 155 (35%), 9727 (31%), 8468 (27%) and 2049 (7%) patients, respectively. The relative benefit of platelet glycoprotein IIb/IIIa receptor blockers did not differ significantly (p = 0.5) between age subgroups (OR (95% CI) for death or myocardial infarction: 0.86 (0.74 to 0.99), 0.90 (0.80 to 1.02), 0.97 (0.86 to 1.10), 0.90 (0.73 to 1.16); overall 0.91 (0.86 to 0.99). ORs for major bleeding were 1.9 (1.3 to 2.8), 1.9 (1.4 to 2.7), 1.6 (1.2 to 2.1) and 2.5 (1.5-4.1). Overall NNT was 105, and overall NNH was 90. The oldest patients had larger absolute increases in major bleeding, but also had the largest absolute reductions of death or myocardial infarction. Patients > or =80 years had half of the NNT and a third of the NNH of patients <60 years. CONCLUSIONS: In patients with NSTE-ACS, the relative reduction of death or non-fatal myocardial infarction with platelet glycoprotein IIb/IIIa receptor blockers was independent of patient age. Larger absolute outcome reductions were seen in older patients, but with a higher risk of major bleeding. Close monitoring of these patients is warranted.

Adult↗
PubMed1998

Reduction in excitability of the auditory nerve following acute electrical stimulation at high stimulus rates: III. Capacitive versus non-capacitive coupling of the stimulating electrodes.

Safe electrical stimulation of neural tissue is typically achieved using charge-balanced biphasic current pulses, which are designed to minimize the generation of direct current (DC) and the production of harmful electrochemical products. However, due to the kinetics of the charge injection process, neural stimulators must also use capacitive coupling or electrode shorting techniques, to ensure DC levels are minimal. Previous studies have reported a reduction in excitability of the auditory nerve following acute simulation at high rates and intensities. Elevated levels of DC were reported in these studies despite using charge-balanced biphasic pulses and electrode shorting. The present study was designed to investigate the extent to which DC contributed to these stimulus induced reductions in auditory nerve excitability. Adult guinea pigs were bilaterally implanted and unilaterally stimulated for two hours using charge-balanced biphasic current pulses and stimulus rates of 200, 400 or 1000 pulses/s (pps) at a stimulus intensity well above clinical levels (0.34 microC/phase). DC levels were controlled using either electrode shorting, or electrode shorting with capacitive coupling. Electrically evoked auditory brainstem responses (EABRs) were recorded before and periodically following the acute stimulation. It was found that the extent of reduction in the EABR amplitude was a function of stimulus rate. While there was little change in the EABR following stimulation at 200 pps, significant post-stimulus reductions in the EABR amplitude were observed at stimulus rates of 400 and 1000 pps during the three hour post-stimulus monitoring period. Stimulation using capacitively coupled electrodes, which eliminated all DCs, showed reductions in EABR amplitudes similar to those observed following stimulation using electrode shorting alone. While there was no significant difference in the extent of reduction in EABR amplitudes for capacitive coupling versus electrode shorting at stimulus rates of 200 pps (P > 0.05) and 400 pps (P > 0.05), there was a significant difference at 1000 pps (P< 0.001). The present findings indicate that the major component of the stimulus induced reductions observed in auditory nerve excitability appear to be associated with stimulus induced neuronal activity, although elevated levels of DC ( > 2.5 microA) can also contribute to these changes. However, although statistically significant, the effects of DC are very small compared to the effects of high rate, high intensity stimulation per se.

Animals↗
PubMed1996

The diagnosis and management of acromegaly: a Canadian consensus report.

OBJECTIVE: To reach a Canadian consensus on the diagnosis and management of acromegaly. OPTIONS DIAGNOSIS: documenting autonomous growth-hormone hypersecretion and imaging of the pituitary. TREATMENT: surgical resection, adjunctive therapy with bromocriptine or octreotide and radiation therapy. OUTCOMES: Reduction of the morbidity and mortality associated with acromegaly. EVIDENCE: Review of international literature. VALUES: Achievement of consensus among a panel of Canadian endocrinologists. BENEFITS, HARMS AND COSTS: Acromegaly is a chronic debilitating condition that is associated with morbidity and mortality. This consensus statement is designed to improve the diagnosis and management of this rare condition in order to minimize the negative outcomes. Costs were not considered. RECOMMENDATIONS: The diagnosis of acromegaly is established by documenting autonomous growth-hormone hypersecretion and by imaging the pituitary. Surgical resection is the cornerstone of treatment; however, adjunctive therapy is often needed. Although growth-hormone reduction is often associated with alleviation of symptoms, an attempt should also be made to normalize levels of growth hormone and its target growth factor, insulin-like growth factor-I (IGF-I). Persistent secretion of excess growth hormone and IGF-I may pose significant long-term health risks. A suggested therapeutic algorithm is provided. The ease of administration of bromocriptine should prompt a trial of therapy with this agent. The subcutaneous use of octreotide is of particular benefit to those patients with persistently high levels of growth hormone and IGF-I that cannot be suppressed by other means. Because acromegaly is relatively rare and complex, its diagnosis and treatment require the concerted efforts of an endocrinologist, an neurosurgeon and a radiation oncologist.

Acromegaly↗
PubMed1989

Regulation of intracellular pH in the myocardium; relevance to pathology.

Intracellular pH affects the contractile function of the heart, metabolic reactions, ion exchange and calcium homoeostasis. Numerous studies have concluded that a fall of extracellular pH, by whatever mechanism, causes a fall of contractility by alteration of intracellular pH. Measurement of cytosolic intracellular pH using microelectrodes has confirmed that earlier deduction. Acidosis reduces the slow calcium current and the release of calcium from the sarcoplasmic reticumul but, because the cytosolic calcium does not fall, the major site of action of hydrogen ions appears to be on the calcium sensitivity of the contractile proteins. In man acidosis can be detected 15 s after the occlusion of a coronary artery and is a major mechanism for the simultaneous loss of contractility in ischaemia. A transient alkalosis is not detected in man but has been reported in isolated heart preparations where ATP consumption is low. An imposed mild respiratory acidosis during hypoxia increases the subsequent recovery of mechanical function on reoxygenation whereas a severe acidosis can be harmful. Acidosis in ischaemic may be advantageous due to a cardioplegic effect, inhibition of transsarcolemmal calcium fluxes or a reduction of mitochondrial calcium overload. Calcium uptake on reperfusion or reoxygenation has been linked to an inward movement of sodium in exchange for hydrogen ions on reperfusion and subsequent sodium-calcium exchange. Such a mechanism in its simplest form cannot account for the similar uptake of calcium on reoxygenation and reperfusion. Acidosis is a cause of early contractile failure in ischaemia but the role of acidosis in causing cell necrosis is not established.

Acidosis↗
PubMed2006

Prey-mediated effects of transgenic canola on a beneficial, non-target, carabid beetle.

Transgenic plants producing insecticidal proteins from Bacillus thuringiensis (Bt) can control some major insect pests and reduce reliance on sprayed insecticides. However, large scale adoption of this technology has raised concerns about potential negative effects, including evolution of pest resistance to Bt toxins, transgene flow from Bt crops to other plants, and harm to non-target beneficial organisms. Furthermore, concern has also been expressed over the effects this technology may have on biodiversity in general. Ecologically relevant risk assessment is therefore required (Risk = Hazard x Exposure). Transgenic plants that produce Bt toxins to kill insect pests could harm beneficial predators. This might occur directly by transmission of toxin via prey, or indirectly by toxin-induced reduction in prey quality (Hazard). To test these hypotheses, we determined the effects of Bt-producing canola on a predatory ground beetle (Pterostichus madidus) fed larvae of diamondback moth (Plutella xylostella) that were either susceptible or resistant to the Bt toxin. Survival, weight gain, and adult reproductive fitness did not differ between beetles fed prey reared on Bt-producing plants and those fed prey from control plants. Furthermore, while Bt-resistant prey was shown to deliver high levels of toxin to the beetle when they were consumed, no significant impact upon the beetle was observed. Subsequent investigation showed that in choice tests (Exposure), starved and partially satiated female beetles avoided Bt-fed susceptible prey, but not Bt-fed resistant prey. However, in the rare cases when starved females initially selected Bt-fed susceptible prey, they rapidly rejected them after beginning to feed. This prey type was shown to provide sufficient nutrition to support reproduction in the bioassay suggesting that Bt-fed susceptible prey is acceptable in the absence of alternative prey, however adults possess a discrimination ability based on prey quality. These results suggest that the direct effects of Bt-producing canola on predator life history was minimal, and that predators' behavioural preferences may mitigate negative indirect effects of reduced quality of prey caused by consumption of Bt-producing plants. The results presented here therefore suggest that cultivation of Bt canola may lead to conservation of non-target predatory and scavenging organisms beneficial in pest control, such as carabids, and may therefore provide more sustainable agricultural systems than current practices. In addition, minimal impacts on beneficial carabids in agro-ecosystems suggest that Bt canola crops are likely to be compatible with integrated pest management (IPM) systems.

Animals↗
PubMed2004

Senescence marker protein-30 is a unique enzyme that hydrolyzes diisopropyl phosphorofluoridate in the liver.

Senescence marker protein-30 (SMP30) was originally identified as a novel protein in the rat liver, the expression of which decreases androgen-independently with aging. We have now characterized a unique property of SMP30, the hydrolysis of diisopropyl phosphorofluoridate (DFP), which is similar to the chemical warfare nerve agents sarine, soman and tabun. Hydrolysis of DFP was stimulated equally well by 1 mM MgCl2, MnCl2 or CoCl2, to a lesser extent by 1 mM CdCl2 but not at all by 1 mM CaCl2. No 45Ca2+-binding activity was detected for purified SMP30, suggesting that SMP30 is not a calcium-binding protein, as others previously stated. Despite the sequence similarity between SMP30 and a serum paraoxonase (PON), the inability of SMP30 to hydrolyze PON-specific substrates such as paraoxon, dihydrocoumarin, gamma-nonalactone, and delta-dodecanolactone indicate that SMP30 is distinct from the PON family. We previously established SMP30 knockout mice and have now tested DFPase activity in their livers. The livers from wild-type mice contained readily detectable DFPase activity, whereas no such enzyme activity was found in livers from SMP30 knockout mice. Moreover, the hepatocytes of SMP30 knockout mice were far more susceptible to DFP-induced cytotoxicity than those from the wild-type. These results indicate that SMP30 is a unique DFP hydrolyzing enzyme in the liver and has an important detoxification effect on DFP. Consequently, a reduction of SMP30 expression might account for the age-associated deterioration of cellular functions and enhanced susceptibility to harmful stimuli in aged tissue.

Aging↗
PubMed2004

Strategies for CT radiation dose optimization.

Recent technologic advances have markedly enhanced the clinical applications of computed tomography (CT). While the benefits of CT exceed the harmful effects of radiation exposure in patients, increasing radiation doses to the population have raised a compelling case for reduction of radiation exposure from CT. Strategies for radiation dose reduction are difficult to devise, however, because of a lack of guidelines regarding CT examination and scanning techniques. Various methods and strategies based on individual patient attributes and CT technology have been explored for dose optimization. It is the purpose of this review article to outline basic principles of CT radiation exposure and emphasize the need for CT radiation dose optimization based on modification of scanning parameters and application of recent technologic innovations.

Adult↗
PubMed2005

Unfractionated and low-molecular-weight heparin as adjuncts to thrombolysis in aspirin-treated patients with ST-elevation acute myocardial infarction: a meta-analysis of the randomized trials.

BACKGROUND: There is uncertainty about the role of intravenous unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in patients with ST-elevation myocardial infarction (STEMI) treated with aspirin and thrombolysis. METHODS AND RESULTS: We performed a meta-analysis of the randomized trials to assess the effect of UFH and LMWH on reinfarction, death, stroke, and bleeding. Fourteen trials involving a total of 25,280 patients were included (1239 comparing intravenous UFH versus placebo or no heparin; 16,943 comparing LMWH versus placebo; and 7098 comparing LMWH versus intravenous UFH). Intravenous UFH during hospitalization did not reduce reinfarction (3.5% versus 3.3%; odds ratio [OR], 1.08; 95% CI, 0.58 to 1.99) or death (4.8% versus 4.6%; OR, 1.04; 95% CI, 0.62 to 1.78) and did not increase major bleeding (4.2% versus 3.4%; OR, 1.21; 95% CI, 0.67 to 2.18) but increased minor bleeding (19.6% versus 12.5%; OR, 1.72; 95% CI, 1.22 to 2.43). During hospitalization/at 7 days, LMWH compared with placebo reduced the risk of reinfarction by approximately one quarter (1.6% versus 2.2%; OR, 0.72; 95% CI, 0.58 to 0.90; number needed to treat [NNT]=167) and death by &10% (7.8% versus 8.7%; OR, 0.90; 95% CI, 0.80 to 0.99; NNT=111) but increased major bleeding (1.1% versus 0.4%; OR, 2.70; 95% CI, 1.83 to 3.99; number needed to harm [NNH]=143) and intracranial bleeding (0.3% versus 0.1%; OR, 2.18; 95% CI, 1.07 to 4.52; NNH=500). The reduction in death with LMWH remained evident at 30 days. LMWH compared with UFH during hospitalization/at 7 days reduced reinfarction by &45% (3.0% versus 5.2%; OR, 0.57; 95% CI, 0.45 to 0.73; NNT=45), did not reduce death (4.8% versus 5.3%; OR, 0.92; 95% CI, 0.74 to 1.13) or increase major bleeding (3.3% versus 2.5%; OR, 1.30; 95% CI, 0.98 to 1.72), but increased minor bleeding (22.8% vs 19.4%; OR, 1.26; 95% CI, 1.12 to 1.43). The reduction in reinfarction remained evident at 30 days. CONCLUSIONS: In aspirin-treated patients with STEMI who are treated with thrombolysis, intravenous UFH has not been shown to prevent reinfarction or death. LMWH given for 4 to 8 days compared with placebo reduces reinfarction by approximately one quarter and death by &10% and when directly compared with UFH reduces reinfarction by almost one half. These data suggest that LMWH should be the preferred antithrombin in this setting.

Aspirin↗
PubMed2006

Therapeutic monitoring of antiepileptic drugs during pregnancy and in the postpartum period: is it useful?

As in all patient populations, epilepsy is common in pregnant women. Consequently, approximately 1 in 200 pregnancies is exposed to antiepileptic drugs (AEDs). Although exposure to AEDs in utero has been associated with an increased risk of major fetal malformations, most women with epilepsy require medication throughout pregnancy, since seizures themselves may be potentially harmful not only for the mother but also for the developing fetus. Physiological changes during pregnancy result in a reduction in the serum concentrations of most AEDs, particularly in late pregnancy. Changes in protein binding lead to a greater reduction in total than free (active) drug concentrations. Pharmacokinetic changes in pregnancy show interindividual variability and are not well understood for most newer AEDs. However, recent studies have shown that changes in lamotrigine clearance are particularly marked, with increases in each trimester and a significant fall in plasma concentrations, leading to consequent breakthrough seizures in some women. Concentrations may then rise precipitously after delivery, leading to symptoms of lamotrigine toxicity. Therapeutic drug monitoring could theoretically guide adjustment of AED dosage to achieve good seizure control while minimising fetal exposure, although there are several limitations to such monitoring. Firstly, there are wide interindividual variations in serum drug concentrations, with seizure control often correlating poorly with a given therapeutic range. Secondly, therapeutic ranges have not been well defined for newer AEDs and their measurement is often not always available. Thirdly, for highly protein-bound drugs, although measurement of free drug concentrations may more accurately reflect drug availability during pregnancy than total drug concentrations, assays for this are not always available and may be unreliable. Thus, it may be useful, prior to pregnancy, to establish the total and free drug concentrations required to achieve optimal seizure control in a given individual. Regular monitoring of AEDs has been advocated in each trimester and shortly after delivery, with adjustment of dosage to avoid seizure precipitation during pregnancy or symptoms of toxicity after birth. More frequent monitoring has been recommended for lamotrigine. However, aggressive drug monitoring of any AED has yet to be proven to be effective in improving seizure control or care. Furthermore, higher doses may be associated with a greater potential for teratogenicity and it is not yet known whether longer term adverse effects may be related to in utero exposure in the latter half of pregnancy. There is limited evidence about the relationship of maternal serum drug concentrations and teratogenicity. While there is a theoretical role for therapeutic drug monitoring in improving the risk-to-benefit ratio of AED therapy during pregnancy, there are many practical limitations. Future work is needed to clarify its role in improving seizure control during pregnancy and identifying serum drug concentrations that may be considered safe for fetal exposure.

Anticonvulsants↗