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Biomedical subjects

S Phillips

Publications and source records attributed to S Phillips.

At least 109 records · Page 6Linked to original sources

Prenatal diagnosis of ring chromosome 6.

An amniocentesis was performed on a gravida 1, para 0 23-year-old female because of high maternal serum alpha-fetoprotein and nuchal thickening/cystic mass apparent on the fetal ultrasound. Detailed ultrasound examination revealed multiple anomalies including brain abnormalities. The fetus was found to have a mosaic female karyotype: 45,XX, - 6/46,XX,r(6) (p25q27) (62 per cent:38 per cent). This is the first report of a prenatally diagnosed case of ring chromosome 6.

Adult↗

Elevation of breath ethanol measurements by metered-dose inhalers.

STUDY OBJECTIVE: Metered-dose inhalers (MDIs) may contain as much as 38% ethanol. We evaluated the effects of ethanol-containing MDIs on breath alcohol testing. DESIGN: Prospective, single-blind, crossover, controlled study. PARTICIPANTS: Three healthy male volunteers 29 to 36 years old. INTERVENTION: We studied three brands: Tornalate, (38% ethanol), Bronkometer, (30% ethanol), and Alupent, (0% ethanol). The effects of each MDI on breath and blood ethanol measurements were evaluated separately. Two puffs of each brand of MDI were administered. Breath ethanol measurements were obtained at baseline and .25, .5, 1, 2, 3, 5, and 10 minutes after MDI use. Blood ethanol measurements were obtained at baseline and 1 and 10 minutes after MDI use. RESULTS: Overall, Tornalate had the highest breath ethanol readings, with a mean ethanol level of 189 mg/dL recorded just after MDI use. Breath ethanol levels subsequently decreased rapidly over time. Mean breath ethanol concentrations were lower after the use of Bronkometer and undetectable after the use of Alupent. Blood ethanol levels were undetectable at all times tested. CONCLUSION: MDIs may cause elevations of breath alcohol above the legal criteria for intoxication. These effects are transient and may be prevented by a 10-minute interval between the use of an MDI and breath alcohol testing.

Administration, Inhalation↗

Adsorption of botulinum toxin to activated charcoal with a mouse bioassay.

STUDY OBJECTIVE: We evaluated the effectiveness of activated charcoal (AC) in adsorbing Clostridium botulinum type A toxin using a mouse bioassay. DESIGN: Prospective, blinded, randomized, controlled animal study. SETTING: Animal care facility. PARTICIPANTS: One hundred forty Swiss/Webster ND-4 strain mice. INTERVENTION: Food contaminated with type A botulinum toxin was homogenized in a phosphate/gel buffer (pH 6.2). The concentrate was diluted by factors of 1:10, 1:50, and 1:100. AC was added to aliquots of the dilutions to a 20% final concentration. The samples were centrifuged, supernatant was removed, and separate groups of mice were injected intraperitoneally with .5 mL of each dilution (those treated with AC and controls untreated with AC). The animals were then observed over 5 days for signs of botulism. RESULTS: None of the 60 animals injected intraperitoneally with dilutions treated with AC was observed to have any signs of botulism. In contrast, deaths were observed in 10 of 20, 9 of 20 and 4 of 20 mice injected with untreated dilutions of 1:100, 1:50, and 1:10, respectively (P < .004). CONCLUSION: In this model, treatment of botulinum toxin with AC before administration resulted in greatly reduced morbidity and mortality.

Adsorption↗

Therapy of brown spider envenomation: a controlled trial of hyperbaric oxygen, dapsone, and cyproheptadine.

STUDY OBJECTIVE: To determine whether hyperbaric oxygen (HBO), dapsone, or cyproheptadine decreases the severity of skin lesions resulting from experimental Loxosceles envenomation. DESIGN: Randomized, blinded, controlled study. SETTING: Animal care facility. INTERVENTIONS: We used New Zealand white rabbits. All groups received 20 micrograms of pooled L deserta venom intradermally. Our control group received 4 ml of a 5% ethanol solution by oral gavage every 12 hours for 4 days. The HBO group received hyperbaric oxygen at 2.5 ATA for 65 minutes every 12 hours for 2 days, plus 5% ethanol solution for 4 days. The dapsone group received dapsone 1.1 mg/kg in 5% ethanol by gavage every 12 hours for 4 days. The cyproheptadine group received cyproheptadine .125 mg/kg in 5% ethanol by gavage every 12 hours for 4 days. RESULTS: Total lesion size and ulcer size were followed for 10 days. The lesions were then excised, examined microscopically, and ranked by the severity of the histopathology. The groups did not differ significantly with respect to lesion size, ulcer size, or histopathologic ranking. CONCLUSION: Given the negative result in this study with adequate power to detect meaningful treatment benefits, we cannot recommend hyperbaric oxygen, dapsone, or cyproheptadine in the treatment of Loxosceles envenomation.

Animals↗

In vitro LAK (lymphokine activated killer) activity following autologous peripheral blood stem cell is significantly greater than that following autologous bone marrow and allogeneic bone marrow transplantation.

LAK activity is known to increase following autologous and allogeneic bone marrow transplant and peripheral blood stem cell transplant (PBSCT). The aim of this study was to directly compare the 3 types of transplant and the LAK activity generated. LAK activity following PBSCT is significantly greater than that following autologous bone marrow transplantation and even allogeneic transplantation up to 8 weeks. The type of killer cells generated is similar for the different types of transplants, with most killing activity following PBSCT due to CD56+ cells, though CD3+ cells also contribute. This study would suggest that attempts to augment the graft-versus-leukaemia effect is more likely to be successful following PBSCT than autologous bone marrow transplantation.

Adolescent↗

Vitreous humor cocaine and metabolite concentrations: do postmortem specimens reflect blood levels at the time of death?

The interpretation of postmortem cocaine concentrations is made in an attempt to estimate drug concentrations present at the time of death and thus infer not only drug presence but drug toxicity. Previous data suggest that changes in postmortem blood cocaine concentrations over time are not predictable and interpretation of cocaine levels should be done with caution. However, these data come from autopsy case series where vital information, such as blood cocaine concentration at the time of death, dose and time since last use, and postmortem interval is often not known. The purpose of this study was to characterize postmortem changes in cocaine and metabolite concentrations relative to premortem concentrations over time at two anatomic sites: peripheral blood and vitreous humor, in a controlled, large animal model. Juvenile swine were given cocaine HCl 10 mg/kg as an IV bolus which resulted in seizures and wide complex tachycardia. Five minutes after cocaine administration, animals were euthanized. At time of death and eight hours postmortem, femoral venous blood and vitreous humor (VH) samples were obtained for quantitation of cocaine, benzoyl ecgonine (BE), and ecgonine methyl ester (EME) by GC/MS. There were no significant increases over time in mean femoral vein concentrations of cocaine or BE. However, a large interanimal variability in direction and magnitude of concentration changes was seen. Mean EME concentrations at the femoral site increased significantly over 8 hours (P < 0.03). Mean VH cocaine concentrations at time of death were significantly lower than corresponding blood concentrations (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Postmortem acetaminophen pharmacokinetics: an experimental study of site and time-dependent concentration changes.

Postmortem blood drug concentrations are obtained routinely for assessment of the cause of mortality. However, the relationship of postmortem drug concentration to blood concentrations at the time of death remains poorly characterized. Using Ketamine sedation, 10 New Zealand white rabbits were sacrificed 20 minutes after oral gavage with liquid acetaminophen 160 mg/kg as a model drug. Blood samples were obtained from peripheral (femoral vein) and central sites (heart & inferior cava) over time and compared with heart blood concentrations obtained at the time of sacrifice. The mean +/- SE antemortem acetaminophen concentration was 63.1 +/- 14.6 mcg/ml. Postmortem central blood concentrations were as follows: T = 3 h: 200.8 +/- 129.2 micrograms/mL, T = 6 h: 100.8 +/- 39.6 micrograms/mL and T = 12 h: 480.8 +/- 128.8 micrograms/mL. Postmortem peripheral site results were: T = 3 h: 50.2 +/- 21.4 micrograms/mL, T = 6 h: 100.8 +/- 18.1 and T = 12 h: 117.7 +/- 37.2 micrograms/mL. Overall, blood acetaminophen concentrations increased significantly over time for central sampling sites. Drug concentration increases seen in the central sampling sites were several times higher than that seen in peripheral blood. Blood samples taken from peripheral sites did not alter significantly. The results of this controlled study were consistent with previous autopsy case series and case reports suggesting that postmortem drug concentrations do not reflect premortem values. Variables affecting postmortem drug concentrations include both postmortem sampling time and anatomic blood collection site.

Acetaminophen↗

Effector mechanisms against asexual erythrocytic stages of Plasmodium.

Evidence for a role for macrophages/monocytes is largely based on in vitro not in vivo observations. Products of activated macrophages particularly tumor necrosis factor-alpha (TNF alpha) are implicated in the killing of parasites. Access of cytokines and other factors might be through intracellular channels in the infected red blood cell. The cytotoxic elements in 'crisis' serum are uncertain but may include TNF, gamma-interferon (IFN gamma), and lipid peroxidases. TNF alpha in excess, contributes to pathology. TNF, acting as a pyrogen and raising body temperature, may moderate parasite density by killing late asexual stages. Nitric oxide and other nitrogen intermediates, products of activated macrophages and a number of other cell types, have been demonstrated both in vitro and in vivo to have a protective role. Phagocytosis of infected erythrocytes and merozoites, enhanced by the presence of immune serum in some systems, has been reported. Killing of parasites by neutrophils is enhanced by immune serum and cytokines TNF alpha, IFN gamma and lymphotoxin. A role for natural killer cells has been suggested. Evidence for antibody-dependent cellular cytotoxicity (ADCC) is controversial. Antibody-dependent cellular inhibitory activity (ADCI) (blood monocytes plus immune IgG) has been described for P. falciparum. Evidence for an important role for complement is conflicting; an involvement in the protective activity of phagocytic cells is reported. Antibody isotypes have been relatively little studied. In murine systems IgG2a may have a role early in the protective immune response followed by IgG1. In P. falciparum ADCI activity is mediated by IgG1 and IgG3, two cytophilic isotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Human envenomation from a wandering garter snake.

Garter snake bites are generally innocuous to human beings. We report a case of human envenomation from the Wandering Garter snake (Thamnophis elegans vagrans). The patient, who was bitten on his right third fingertip, rapidly developed local edema, ecchymosis, and hemorrhagic vesicles. Systemic signs and symptoms did not develop. The clinical picture was similar to that in three previous patients with Thamnophis envenomation in that clinical signs followed a prolonged bite. Thamnophis species have Duvernoy's glands, which may be analogous to venom glands in Crotalidae (pit viper) species. The progressive local effects produced by secretions of these glands may be confused with early Crotalidae envenomation.

Adolescent↗

Methamphetamine toxicity prevented by activated charcoal in a mouse model.

STUDY OBJECTIVE: To determine the effectiveness of activated charcoal in preventing toxicity from oral methamphetamine HCI. DESIGN: Randomized, prospective, nonblinded, controlled animal study. SETTING: Animal care facility. PARTICIPANTS: CD-1 male mice. INTERVENTIONS: Mice were given 100 mg/kg methamphetamine HCI (lethal dose 60) in water by oral gavage. Within 1 minute of methamphetamine administration, mice received either 1 g/kg activated charcoal or an equivalent volume of water as control. MEASUREMENTS AND MAIN RESULTS: Mice were observed for time to onset of symptoms (piloerection, agitation, and tremor) and mortality at 1, 24, and 48 hours. Activated charcoal delayed onset of symptoms (5.53 +/- 1.25 minutes versus 4.27 +/- 1.22 minutes, P < .002) and decreased mortality compared to controls at 1 hour (1 of 20 versus 10 of 20, P < .003) and 24 hours (five of 20 versus 12 of 20, P < .05). There was no difference between groups in mortality at 48 hours. CONCLUSION: A single dose of activated charcoal given after oral methamphetamine delayed onset of toxicity and decreased early mortality in mice. There was no effect on overall mortality.

Animals↗

Diagnosis of vascular dementia: Consortium of Canadian Centres for Clinical Cognitive Research concensus statement.

Interest in vascular causes for cognitive impairment is increasing, in recognition that such causes are common, and possibly preventable. This has led to attempts to better define vascular dementia and its natural history. Several sets of criteria for the diagnosis of vascular dementia have been proposed. We provide a brief overview of the background to the initiation of a Canadian consensus conference, established by the Consortium of Canadian Centres for Clinical Cognitive Research (C5R) and report the conclusions reached at that conference. To date, no one set of criteria is demonstrably superior to another; we have therefore not endorsed any of the competing sets, nor have we recommended our own. Instead we suggest that empiric studies are required to establish valid criteria. A diagnostic checklist, which combines existing criteria and additional data, is attached for clinicians wishing to participate in such studies.

Canada↗

Preoperative fasting for paediatric anaesthesia.

Preoperative fasting was introduced to reduce the risk and severity of aspiration pneumonitis. Adequate time (6h) must still be allowed before operation for solid foods to be emptied from the stomach. However, the overwhelming weight of evidence supports the practice of reducing the duration of the preoperative fluid fast for elective paediatric surgical patients [3, 15]. In children allowed free, clear fluids until 2 h before the scheduled time of anaesthesia, gastric contents and thus the risk of aspiration pneumonitis appears to be similar to those children who have endured a longer fast. Potential benefits of reduced thirst, better perioperative experience, improved compliance and reduced hypoglycaemia may be seen. Patients at risk of GOR and aspiration pneumonitis, including those presenting for emergency surgery, must receive special consideration. As aspiration pneumonitis is so rare, careful reporting of complications potentially related to a reduced fasting period is necessary.

Adolescent↗

Educational visiting and hypnosedative prescribing in general practice.

Public concern about the prescription of hypnosedative drugs (mostly benzodiazepines) led to a controlled trial of an educational intervention to promote rational prescribing by general practitioners (GPs). This paper describes the educational intervention and its process evaluation. In urban and rural New South Wales 137 GPs were visited in office hours by a GP or pharmacist who had undergone communication skills training. Material offered to GPs included relaxation tapes and a booklet of problem-orientated management guidelines. The interview had three stages: rapport was established, then educational material was introduced and finally the visitor sought the doctor's agreement to review five patients on long-term benzodiazepines. The visits were well received. Several measures were composed to reflect doctors' motivation and interest in non-drug management; there was virtually no correlation between any of these process measures and the trial outcome: a change in prescribing behaviour. Self-rating of benzodiazepine prescribing greatly underestimated actual self-reported incidents of prescribing. We interpret this as a reminder that we do not always do what we mean to do, and that we do not always do what we think we do.

Anti-Anxiety Agents↗

Surveillance for stroke in Canada.

The goal of surveillance is to identify patterns of disease occurrence, detect disease outbreaks, develop clues about possible risk factors, find persons that need further investigation, and anticipate health service needs. Two sources of data are available for the purposes of surveillance: primary data, such as those arising from health surveys or local population-based registries; and secondary data, arising from large administrative databases. The effectiveness of any program to monitor the health of a community can be judged by the application of three "r's": right (accuracy), reasonable (cost) and rapid (speed). Programs using primary sources of data satisfy only one of the three "r's," that of accuracy. Programs using secondary sources sacrifice accuracy for speed and cost. The challenge for Canada in setting up surveillance for stroke is that there is a relatively small population unevenly distributed over a very large geographical area. To date, surveillance in Canada has consisted of a combination of individually initiated research projects and government sponsored programs. The main focus has been to tackle the issue of the accuracy of the large databases by validating the discharge codes listed in the provincial hospital discharge databases. Three provinces have carried out independent validation studies yielding remarkably similar results, and this lends confidence that hospital discharge databases will provide a means of carrying out surveillance for at least this one aspect of stroke. It is likely that any program for stroke surveillance in Canada will be multifaceted, involving the use of large computerized databases supplemented by hospital-based registries set up in a few highly motivated local centres. Stroke surveillance will best be accomplished by a joint effort between government and researchers to ensure that the end product is of high quality and will meet the needs of improving the health of Canadians.

Aged↗

Pediatric gastrointestinal decontamination in acute toxin ingestion.

The appropriate implementation of the various modalities of gastrointestinal (GI) decontamination is critical in the management of the pediatric patient who is examined in the emergency department or private office after an acute ingestion. Gastrointestinal decontamination includes gastric lavage, syrup of ipecac, activated charcoal, and whole bowel irrigation. Clinical studies have delineated the role and efficacy of these procedures. Trends in GI decontamination place less emphasis on ipecac and gastric lavage and more emphasis on activated charcoal alone in the patient with a mild overdose. Gastric lavage is indicated in serious ingestion and is most effective if done soon after the exposure. Whole bowel irrigation is the newest addition and has important clinical use in the treatment of serious iron ingestions as well as in older adolescent cocaine body suffers and packers. Indications and contraindications of the various forms of GI decontamination are discussed and relevant clinical studies are reviewed.

Charcoal↗

Identification of an uncommon haptoglobin type using DNA and protein analysis.

The inherited variations in haptoglobin phenotypes are attributed to the homozygous and heterozygous combinations of three common autosomal alleles: HP*1F, HP*1S and HP*2. HP*1F and HP*1S encode polypeptides that differ by two amino acids at positions 51 and 53. The formation of HP*2 is postulated to have resulted from a breakage and subsequent reunion event at non-homologous positions of two HP*1 alleles. The most common form of HP*2 is HP*2FS in which the 5' end of HP*2 resembles HP*1F and the 3' end resembles HP*1S. Homologous crossing over between HP*2 and either an HP*1F or HP*1S allele in HP*2/HP*1 heterozygotes can change the usual type of HP*2 to three other forms: HP*2SS, HP*2FF or HP*2SF. We describe a nuclear family in which the uncommon genotype HP*2SS is one parent caused initial confusion in assigning genotypes to the rest of the nuclear family. The data demonstrate the need for a cautious approach when deducing haptoglobin genotypes from molecular analysis alone.

Alleles↗