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Biomedical subjects

A Lynch

Publications and source records attributed to A Lynch.

At least 37 records · Page 2Linked to original sources
PubMed1997

Ethics teaching and learning in pediatric training: development of a curriculum.

The Royal College of Physicians and Surgeons of Canada has stated that residency programs "must provide opportunities for residents to gain an understanding of the basic principles of biomedical ethics as it relates to the specialty." This article presents the steps taken to develop a curriculum for teaching and learning biomedical ethics in Canadian pediatric residency programs, and to provide a model for teaching ethics in this context. Using literature reviews, and opinion surveys of departmental chairpersons, pediatric residents, and practising pediatricians across Canada, we have developed a teachers' handbook to help faculty members in teaching ethics. It can also be used as a tool to enhance faculty development in ethics. The manual is to be distributed to all pediatric training programs throughout Canada in 1997, and its use will be evaluated over the subsequent year. It offers a prototype that is adaptable to Royal College programs other than pediatrics.

Canada↗
PubMed1996

Chemical methods for assessing systemic exposure to dietary heterocyclic amines in man.

A significant proportion of the mutagenic material present in cooked beef is accounted for by 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) which are formed during the cooking of meat. N-hydroxylation catalyzed by CYP1A2 is the major pathway of metbolism of MeIQx and PhIP and is solely responsible for the generation of mutagenic species. Assays for MeIQx and PhIP in foods and body fluids were developed utilising gas chromatography/mass spectrometry with stable isotope labelled analogues as internal standards. Studies using these assays have demonstrated that both MeIQx and PhIP are well absorbed and extensively metabolised following ingestion of amine-containing beef by humans. Studies in which furafylline, a potent and selective inhibitor of human CYP1A2, was administered before ingestion of beef revealed that more than 90% of MeIQx and 70% of PhIP are N-hydroxylated in vivo, probably pre-systemically in the liver. The results demonstrate that unchanged MeIQx and PhIP in urine are accurate and sensitive measures of systemic exposure to the amines.

Carcinogens↗
PubMed1996

Alterations of end-tidal carbon dioxide during the intrahospital transport of children.

OBJECTIVE: To determine the effect of manual ventilation during intrahospital transport on end-tidal carbon dioxide concentrations in children. DESIGN: Prospective study in children who required tracheal intubation and mechanical ventilation/ hyperventilation to maintain an arterial partial pressure of CO2 (PaCO2) of 25 to 30 torr for control of intracranial pressure. SETTING: Pediatric intensive care unit. INTERVENTION: During patient transport with manual ventilation, end-tidal CO2 was monitored with a side-streaming aspirating, infrared device. The person responsible for manual ventilation was informed of the current ventilator settings and the need to maintain a PaCO2 of 25 to 30 torr, but was not allowed to see the end-tidal CO2 monitor. RESULTS: The study population included 12 patients ranging in age from seven months to 14 years (average age 6.9 years) and in weight from 6.5 to 57 kg (average weight 28.9 kg). A total of 1716 end-tidal CO2 values were recorded during 286 minutes of monitoring. Five hundred and thirty-one (31%) of the readings were in the intended range of 25 to 30 torr. Four hundred (23%) were less than 20 torr, 665 (39%) were in the 20 to 24 torr range, and 119 (6.3%) were greater than 30 torr. Only five were greater than 40 torr. CONCLUSIONS: Unintentional hyperventilation occurs during the intrahospital transport of children. End-tidal CO2 values less than 25 torr were noted 62% of the time.

Adolescent↗
PubMed1996

Nicardipine to control mean arterial pressure during extracorporeal membrane oxygenation.

The authors present the use of nicardipine to control mean arterial pressure (MAP) in a 19-month-old boy who required venoarterial extracorporeal membrane oxygenation for 11 days for treatment of hydrocarbon aspiration. Nicardipine is an intravenously administered dihydropyridine calcium channel antagonist whose primary physiological action includes vasodilatation. Unlike other calcium channel blockers, it has limited effects on the inotropic and dromotropic function of the myocardium. Nicardipine was started at 5 micrograms.kg-1.min-1 and within five min lowered the MAP from a maximum value of 108 mmHg back to the baseline range of 60 to 80 mmHg. Once the MAP had returned to baseline values, infusion requirements varied from 1 to 3 micrograms.kg-1.min-1 to maintain the MAP at 60 to 80 mmHg during the 11 days of ECMO. No increase in dose requirements were noted during the 11 days.

Antihypertensive Agents↗
PubMed1995

PTB domains of IRS-1 and Shc have distinct but overlapping binding specificities.

PTB domains are non-Src homology 2 (SH2) phosphotyrosine binding domains originally described in the receptor tyrosine kinase substrate, Shc. By serial truncation, we show that a 174-residue region of Shc p52 (33-206) has full PTB activity. We also show that a 173-residue region of insulin receptor substrate-1 (IRS-1; residues 144-316) has related PTB activity. In vitro both domains bind directly to activated insulin receptors. Binding is abrogated by substitution of Tyr-960 and selectively inhibited by phosphopeptides containing NPXY sequences. Phosphopeptide assays developed to compare PTB domain specificities show that the Shc PTB domain binds with highest affinity to psi XN beta 1 beta 2 pY motifs derived from middle T (mT), TrkA, ErbB4, or epidermal growth factor receptors (psi = hydrophobic, beta = beta-turn forming); the IRS-1 PTB domain does not bind with this motif. In contrast, both the Shc and IRS-1 PTB domains bind psi psi psi XXN beta 1 beta 2pY sequences derived from insulin and interleukin 4 receptors, although specificities vary in detail. Shc and IRS-1 are phosphorylated by distinct but overlapping sets of receptor-linked tyrosine kinases. These differences may be accounted for by the inherent specificities of their respective PTB domains.

3T3 Cells↗
PubMed1995

Pancuronium infusion for neuromuscular block in children in the pediatric intensive care unit.

When neuromuscular blockade becomes necessary in the intensive care unit, there are several options available in regard to both the drug and the mode of delivery (continuous versus intermittent administration). Despite extensive experience with intermediate acting drugs such as atracurium or vecuronium, these muscle relaxants are costly and may account for a significant portion of the pharmacy charges. We undertook an open label study to evaluate the efficacy and dosing requirements for a less costly drug, pancuronium. The study group included 25 patients ranging in age from 3 mo to 17 yr and in weight from 3.2 to 68 kg. If the patient had not previously received neuromuscular blocking agents (NMBAs), pancuronium was administered as a bolus dose of 0.1 mg/kg followed by a continuous infusion of 0.05 mg.kg-1.h-1. A nerve stimulator was applied to either the ulnar or peroneal nerve and a standard train-of-four (TOF) was monitored every 2 h. In patients that had previously received other NMBAs, no bolus dose of pancuronium was administered and the infusion was started at 0.05 mg.kg-1.h-1. The pancuronium infusion was increased or decreased by increments of 0.01 mg.kg-1.h-1 to maintain one to two twitches of the TOF. In patients that required an increase in the infusion rate, an additional bolus dose equivalent to the current hourly rate was administered and then followed by the increase in the infusion rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Coexpression of TGF alpha, epidermal growth factor receptor, and P-glycoprotein in normal and benign diseased breast tissues.

Twenty-four normal or benign breast tissues were examined for the expression of transforming growth factor-alpha (TGF alpha), epidermal growth factor receptor (EGFR), and P-glycoprotein, the product of the mdr-1 gene. Specific staining for all three proteins was observed in the majority of the samples. P-glycoprotein staining was present in most (88%), and confined to the lumenal surface of the ductal epithelium. Membranous EGFR expression was observed in epithelial cells in 92% of the specimens and 42% displayed both myoepithelial and epithelial cell staining. TGF alpha staining was intense and uniformly distributed through the cytoplasm (96%). Coexpression of EGFR, TGF alpha, and P-glycoprotein in normal human breast tissues suggests a role for each of those proteins in normal breast physiology. An interaction may be present in normal breast tissue between the EGF receptor pathway and P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Distribution of beta-amyloid protein in the brain following severe head injury.

Deposits of beta-amyloid protein (beta AP) can be found in the brains of 30% of fatally head-injured patients; they have been found in children and after survival times of only 4 h. The principal aims of this study were to map the distribution of beta AP in 14 patients aged 65 years or less in whom it was known that the protein had been deposited, and to correlate its distribution with the pathologies of traumatic brain injury. The results show that beta AP is widely distributed, and that there is no correlation between its presence and cerebral contusions, intracranial haematoma, axonal injury, ischaemic brain damage, brain swelling or the pathology of raised intracranial pressure. These findings suggest that the deposition of beta AP is a consequence of the acute phase response of nerve cells to stress in susceptible individuals. Further studies will be required to establish the possible relationship between the deposition of beta AP following head injury and the molecular neuropathology of Alzheimer's disease.

Adolescent↗
PubMed1995

Systemic exposure to dietary heterocyclic amines in man.

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-I-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are formed during the cooking of meat and account for a significant proportion of the mutagenic material present in cooked beef. The amines are not directly mutagenic but are converted to active intermediates by P450. Studies in vitro with human liver have shown that N-hydroxylation catalyzed by CYP1A2 is the major pathway of oxidation of MeQx and PhIP and is solely responsible for the generation of mutagenic species. In the studies reported in this paper it is demonstrated that both MelIQx and PhIP are well absorbed and extensively metabolized following ingestion of amine-containing beef by humans. Experiments with furafylline, a potent and selective inhibitor of human CYP1A2, reveal that more than 90% of MeIQx and 70% of PhIP are N-hydroxylated in vivo, probably presystemically in the liver.

Animals↗
PubMed1994

Biorhythms and chronotherapy in cardiovascular disease.

Recent findings about the effects of biorhythms on cardiovascular disorders are reviewed, and their implications for drug therapy are discussed. The chronobiological approach to physiology evaluates time-dependent changes in biological functions and considers those changes to be multifactorial. Characterization of disease states with this approach allows more accurate determination of the times when patients are at highest risk and therefore in greatest need of preventive measures; it also provides a mechanism for designing optimal drug regimens. There is evidence of circadian variations in the occurrence of myocardial ischemia, acute myocardial infarction, ventricular tachycardia, and sudden cardiac death. Many cardiovascular disorders occur with greatest frequency between 0600 and 1200 in the general population. Blood pressure, too, follows a distinct circadian pattern. Factors affecting circadian variations in cardiovascular disorders include physiological determinants, such as heart rate, catecholamine release, and platelet aggregation--which themselves vary cyclically--and exogenous factors, such as mental stress, anxiety, and physical activity. In chronotherapy, circadian variations in disease states and in the pharmacodynamic properties of drugs are exploited to improve prevention and treatment. Conditions in which research suggests a chronotherapeutic approach may be advantageous include thromboembolism, hypertension, stable exertional angina, variant angina, sustained ventricular tachycardia, and acute myocardial infarction. Information on circadian patterns in the occurrence of many cardiovascular disorders is enabling clinicians to tailor treatment in ways that may lead to improved patient outcomes.

Cardiovascular Diseases↗
PubMed1994

Antiphospholipid antibodies in predicting adverse pregnancy outcome. A prospective study.

OBJECTIVE: To determine if the presence of antiphospholipid antibody (aPL) in healthy pregnant women is associated with adverse pregnancy outcome, including 1) intrauterine fetal loss, 2) maternal pregnancy complications, 3) low birth weight, and 4) low 5-minute Apgar scores. DESIGN: Prospective cohort study in women with normal pregnancies. SETTING: Obstetrics clinic at the University of Colorado Health Sciences Center. PATIENTS: Eligible patients included 451 low-risk, nulliparous pregnant women who came to the obstetrics clinic before 25 weeks gestation; 408 were enrolled and 389 had blood drawn at the first prenatal visit and completed clinical follow-up. MEASUREMENTS: Blood for six aPL measures was drawn at the first prenatal visit and for 239 patients at delivery. RESULTS: Ninety-five patients (24.4%) had elevated aPL levels by one or more measures at the first prenatal visit: 15.8% of the aPL-positive and 6.5% of the aPL-negative patients experienced fetal loss (relative risk, 2.44; 95% CI, 1.29 to 4.62). However, an elevated IgG anticardiolipin antibody level at the first prenatal visit was the only aPL measurement that was significantly associated with fetal loss (relative risk, 3.5; CI, 1.56 to 8.07). Adjustment for confounding variables decreased the relative risk of aPL for fetal loss slightly, but the difference remained statistically significant. Neither a positive aPL result at the initial visit nor a positive result at delivery was associated with maternal complications of pregnancy, low birth weight, or low Apgar scores. CONCLUSIONS: Patients with elevated aPL levels at their initial prenatal visit had an increase in fetal loss but no increase in maternal pregnancy complications, low birth weight, or low Apgar scores. Immunoglobulin G anticardiolipin antibody was the only single test of aPL significantly associated with fetal loss.

Abortion, Spontaneous↗
PubMed1994

Beta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer's disease.

In a recent preliminary study it was reported that a severe head injury resulted in the deposition of beta amyloid protein (beta AP) in the cortical ribbon of 30% of patients who survived for less than two weeks. Multiple cortical areas have now been examined from 152 patients (age range 8 weeks-81 years) after a severe head injury with a survival time of between four hours and 2.5 years. This series was compared with a group of 44 neurologically normal controls (age range 51 to 80 years). Immunostaining with an antibody to beta AP confirmed the original findings that 30% of cases of head injury have beta AP deposits in one or more cortical areas. Increasing age seemed to accentuate the extent of beta AP deposition and potential correlations with other pathological changes associated with head injury were also investigated. In addition, beta amyloid precursor protein (beta APP) immunoreactivity was increased in the perikarya of neurons in the vicinity of beta AP deposits. The data from this study support proposals that increased expression of beta APP is part of an acute phase response to neuronal injury in the human brain, that extensive overexpression of beta APP can lead to deposition of beta AP and the initiation of an Alzheimer disease-type process within days, and that head injury may be an important aetiological factor in Alzheimer's disease.

Adolescent↗
PubMed1994

Ethics in dental research. Publication of research: the ethical dimension.

If science is to achieve its goal, i.e., advancement of human well-being, the results of scientific research must be made available. When such results are presented, that presentation must be 'ethical'; it must conform to recognized standards of honesty, originality, and fairness. Unfortunately, not all such presentations conform to these standards; the public and scientific community alike are becoming ever more concerned about duplication in publication, about illegitimate claims to authorship, and about misleading use of statistics in presentation of experimental results. Certain of these 'unethical' practices can be eliminated or minimized by education, institutional practice, and requirements set by scientific journals. In the end, however, 'ethical publication' will depend on the 'ethical investigator'--an individual who has professed dedication to truth and the well-being of mankind.

Authorship↗
PubMed1994

Ethical issues in bone marrow transplantation: a nursing perspective.

It is clear that there are many challenges facing health professionals who care for this patient population. The close collaboration with the physicians on our team ensures that patients and nurses receive clear communication about the goals of the treatment plan. It is our hope that by sharing these insights we challenge other health care teams to provide patient and family-centred care which is compassionate towards the needs of those who depend so greatly on us.

Bone Marrow Transplantation↗
PubMed1992

Increased levels of soluble low-affinity Fc gamma receptors (IgG-binding factors) in the sera of tumour-bearing mice.

Soluble forms of low affinity Fc gamma receptors (Fc gamma R), also called IgG-binding factors (IgG-BF), have been shown to play a regulatory role in immune responses. By using an immunodot assay with the anti-mouse Fc gamma R MoAb, 2.4G2, the levels of IgG-BF have been measured in the sera of mice bearing syngeneic tumours of lymphoid or non-lymphoid origin or in mice injected with high doses of murine IgG. These sera contained large amounts of IgG-BF as compared with controls. In the case of mice bearing IgG2a- or IgG2b-secreting hybridomas or lymphomas, serum IgG-BF increased progressively with tumour size and serum monoclonal IgG concentration, reaching 4-12 times the normal levels. A less than three-fold increase was found in mice bearing an IgG1-secreting hybridoma or tumours which do not secrete IgG (IgA-secreting hybridoma, non-immunoglobulin-secreting lymphoid tumours or melanoma) or in mice injected with 9 mg of monoclonal IgG2a. The enhancement of serum IgG-BF levels was independent of the expression of Fc gamma R by the tumour cells, suggesting that the majority of IgG-BF secreted in response to tumours was produced by the host rather than by the tumour. The increased production of IgG-BF may participate in the control of tumour growth and in the modulation of the host immune responses in tumour-bearing animals.

Animals↗
PubMed1991

beta A4 amyloid protein deposition in brain after head trauma.

Previous reports have suggested that both repetitive head trauma and a single injury can be associated with the presence of diffuse beta A4 amyloid protein plaques in long-term survivors. We have studied sixteen patients (aged 10-63 years) who sustained head injury and survived for only 6-18 days. Immunostaining with an antibody to beta A4 amyloid showed extensive deposits of the protein in the cortex in six of the sixteen patients (38%). Thus, severe head injury can trigger beta A4 deposition in the brain within days.

Adult↗