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Biomedical subjects

A Lynch

Publications and source records attributed to A Lynch.

At least 19 recordsLinked to original sources
PubMed2001

The anti-inflammatory cytokine, interleukin (IL)-10, blocks the inhibitory effect of IL-1 beta on long term potentiation. A role for JNK.

Several effects of the proinflammatory cytokine, interleukin-1 beta (IL-1 beta), have been described in the central nervous system, and one area of the brain where marked changes have been reported is the hippocampus. Among these changes are an IL-1 beta-induced inhibition of long term potentiation (LTP) in perforant path-granule cell synapses and an attenuation of glutamate release in synaptosomes prepared from the hippocampus. Evidence suggests that, at least in circulating cells, the anti-inflammatory cytokine, IL-10, antagonizes certain effects of IL-1. We investigated the effect of IL-10 on IL-1 beta-induced inhibition of LTP and glutamate release. The evidence presented indicates that IL-1 beta stimulates the stress-activated protein kinase, c-Jun-activated protein kinase (JNK), and IL-1 receptor-associated kinase, which may explain its inhibitory effect on release and LTP, and that IL-10 reversed the IL-1 beta-induced stimulation of JNK activity and inhibition of release and LTP. We observed that IL-10 abrogated the stimulatory effect of IL-1 beta on superoxide dismutase activity and reactive oxygen species production, whereas the H(2)O(2)-induced inhibition of LTP was also blocked by IL-10. We present evidence that suggests that the action of IL-10 may be mediated by its ability to induce shedding of the IL-1 type I receptor.

Animals↗
PubMed2001

Assisted reproductive interventions and multiple birth.

OBJECTIVE: To investigate the contributions of ovulation-inducing drugs and assisted reproductive technologies to multiple birth. METHODS: This historic prospective study was conducted in a cohort of 13,151 women who delivered after 20 weeks' gestation between October 1996 and December 1999. The study setting was a Colorado health maintenance organization. Cases were women who were pregnant as a result of exposure to treatment with either assisted reproductive technologies or ovulation induction in the absence of assisted reproductive technologies. The main outcome measure was multiple birth. RESULTS: There was a significant association between assisted conception and multiple birth. Compared with women with naturally conceived pregnancies, there was a 25-fold likelihood (95% confidence interval 18, 35, P <.001) of multiple birth among women exposed to any of those treatments. In the total cohort the proportion of multiple births attributable to those treatments was 33%. After adjusting for the use of assisted conception and other covariates, we found no association between advanced maternal age and multiple birth. CONCLUSION: In this cohort, assisted reproductive interventions were strongly associated with multiple birth. Although a higher proportion of older women sought assisted reproductive technologies, we did not find an independent relationship between advanced maternal age and multiple birth. The increasing number of multiple births attributable to assisted conception raises public health concerns regarding multiple gestation-related maternal and infant morbidities.

Adolescent↗
PubMed2001

Evidence that interleukin-1beta and reactive oxygen species production play a pivotal role in stress-induced impairment of LTP in the rat dentate gyrus.

Long-term potentiation (LTP) in both area CA1 and the dentate gyrus is attenuated by stress and the evidence is consistent with the view that this is a consequence of increased activation of glucocorticoid receptors, in the hippocampus, following the stress-induced increase in circulating corticosterone. It has been shown that expression of the pro-inflammatory cytokine, interleukin-1beta (IL-1beta), is increased in hippocampus in response to stress; this finding together with the observation that IL-1beta exerts an inhibitory effect on LTP, suggests that IL-1beta may play a key role in mediating this inhibitory effect of stress on LTP. In this study, we explore this possibility and report that stress is also associated with increased reactive oxygen species production. The evidence presented supports the view that this is secondary to the stress-induced increase in IL-1beta concentration, as IL-1beta increased activity of superoxide dismutase and increased reactive oxygen species accumulation in hippocampus in vitro. We report that the inhibitory effect of stress on LTP is mimicked by H2O2, which increases reactive oxygen species accumulation, and by IL-1beta, the effect of which is overcome by the antioxidant, phenylarsine oxide. The hypothesis that the stress-induced increase in reactive oxygen species production may underlie the suppression of LTP is further supported by the finding that the effect of stress is abrogated by dietary manipulation with antioxidant vitamins E and C.

Animals↗
PubMed2001

Psychopharmacologic treatment of adolescent depression.

Child and adolescent depression is one of the greatest health concerns in our society today. This article critically reviews the literature on the psychopharmacologic treatment of adolescent depression. Although double-blind studies have failed to show the efficacy of tricyclic antidepressants, more recent evidence has emerged for the use of selective serotonin reuptake inhibitors in this population. However, placebo-controlled, double-blind studies are limited, and many of the other newer antidepressants have yet to be investigated in treating adolescent depression. Nonetheless, antidepressants are widely prescribed to these populations, and psychiatric nurses are actively involved in assessing and monitoring the need for these medications in adolescents.

Adolescent↗
PubMed2001

Aortic pulse wave velocity as a marker of cardiovascular disease in subjects over 70 years old.

BACKGROUND: Aortic pulse wave velocity (PWV) is a significant and independent predictor of cardiovascular diseases (CVD) in hypertensive subjects and in patients with end-stage renal disease, but its contribution to cardiovascular risk in subjects between 70 and 100 years old has never been tested. PATIENTS: A cohort of 124 subjects (mean age: 87 +/- 7 years) was studied in two geriatric departments in a Paris suburb. Together with sphygmomanometric blood pressure measurements, aortic PWV was measured using a validated automatic device. RESULTS: Blood pressure, heart rate and body mass index, but not age, explained 48% of the PWV variability in this cohort. Furthermore, PWV was the major factor predicting the presence of CVD. The adjusted odds ratio was 17.44 (95% confidence intervals: 2.52-120.55). Antihypertensive drug therapy and low plasma albumin level had only an additive role. Blood pressure, particularly pulse pressure, had no predictive value. CONCLUSION: In 70-100-year-old subjects, aortic PWV is a strong independent marker of CVD, a finding that remains to be to confirmed by long-term longitudinal studies.

Aged↗
PubMed2000

Swelling and delamination of multi-electrode sensor arrays studied by variable-pressure scanning electron microscopy.

Multi-electrode sensor arrays are made of soft and wet materials not easily examined by most microscopic techniques. In this paper, we have demonstrated that low-vacuum scanning electron microscopy (LVSEM) and energy-dispersive X-ray analysis (EDX) are adequate for studying the hydration, swelling, and possible delamination of multi-electrode sensor arrays. We found that the LVSEM environment had no detectable effect on the morphology of Na(+), K(+), and Ca(++) sensors, and EDX analysis indicated that all three membranes have similar compositions. However, once hydrated, the sensors exhibited different behaviors. The K(+) and Ca(++) sensors swelled more than the Na(+) sensor did. This swelling is due principally to water sorption in the membrane. We believe that the larger thickness of the K(+) and Ca(++) membrane is partly responsible for the observed swelling effect. A simple Griffith analysis of the interface rupture confirms the experimental evidence that these thicker membranes also are more prone to delamination failure.

Biocompatible Materials↗
PubMed2000

Point-of-need diagnosis of cystic fibrosis using a potentiometric ion-selective electrode array.

The novel approach of using a micro-sensor array of miniaturised solid-state ion-selective electrodes to analyse sweat samples for sodium, potassium and chloride simultaneously is described. The array, incorporated into a miniature flow cell which is linked to a portable PC for data acquisition, constitutes a small, portable, and simple to use analytical instrument. Samples are passed through the flow cell and over the array and an immediate potentiometric response is obtained, which can be equated to the concentrations of sodium, chloride, potassium and other parameters in the sweat sample. Used here in conjunction with a Wescor Macroduct sweat sampling unit, it promises a much simplified, much less expensive procedure for sweat analysis than the procedures currently in common use.

Chlorine↗
PubMed1999

Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure.

OBJECTIVES AND BACKGROUND: To determine whether inhaled nitric oxide (iNO) therapy can attenuate the progression of lung disease in acute hypoxemic respiratory failure, we performed a multicenter, randomized, masked, controlled study of the effects of prolonged iNO therapy on oxygenation. We hypothesized that iNO therapy would improve oxygenation in an acute manner, slow the rate of decline in gas exchange, and decrease the number of patients who meet pre-established oxygenation failure criteria. STUDY DESIGN: A total of 108 children (median age 2.5 years) with severe acute hypoxemic respiratory failure from 7 centers were enrolled. After consent was obtained, patients were randomized to treatment with iNO (10 ppm) or mechanical ventilation alone for at least 72 hours. Patients with an oxygenation index >/=40 for 3 hours or >/=25 for 6 hours were considered treatment failures and exited the study. RESULTS: Patient age, primary diagnosis, pediatric risk of mortality score, mode of ventilation, and median oxygenation index (35 +/- 22 vs 30 +/- 15; iNO vs control; mean +/- SEM) were not different between groups at study entry. Comparisons of oxygenation indexes during the first 12 hours demonstrated an acute improvement in oxygenation in the iNO group at 4 hours (-10.2 vs -2.7, mean values; P <.014) and at 12 hours (-9.2 vs -2.8; P <.007). At 12 hours 36% of the control group met failure criteria in contrast with 16% in the iNO group (P <.05). During prolonged therapy the failure rate was reduced in the iNO group in patients whose entry oxygenation index was >/=25 (P <.04) and in immunocompromised patients (P <.03). CONCLUSIONS: We conclude that iNO causes an acute improvement in oxygenation in children with severe AHRF. Two subgroups (immunocompromised and an entry oxygen index >/=25) appear to have a more sustained improvement in oxygenation, and we speculate that these subgroups may benefit from prolonged therapy.

Administration, Inhalation↗
PubMed1999

Association of antibodies to beta2-glycoprotein 1 with pregnancy loss and pregnancy-induced hypertension: a prospective study in low-risk pregnancy.

OBJECTIVE: To determine whether higher levels of anti-beta2-glycoprotein 1 before 25 weeks' gestation are independently associated with either pregnancy loss or pregnancy-induced hypertension. METHODS: Serum samples for the immunoglobulin (Ig) G and IgM isotypes of anti-beta2-glycoprotein 1, anticardiolipin antibody, and antiphosphatidylserine were collected from 325 low-risk nulliparas who presented for prenatal care before 25 weeks' gestation. This cohort was followed prospectively for the development of pregnancy loss and pregnancy-induced hypertension. RESULTS: The adjusted odds ratios (OR) and 95% confidence intervals (CI) of elevated antiphospholipid antibody levels for pregnancy loss were: IgG anti-beta2-glycoprotein 1, OR 1.2 (CI 0.5, 2.8); IgG anticardiolipin antibody, OR 8.4 (CI 2.3, 31); and IgG antiphosphatidylserine, OR 5.2 (CI 1.4, 18.7). The relative risks of pregnancy loss for all IgG antiphospholipid antibodies were higher among women who had blood collected after 10 weeks' gestation compared with those studied before 10 weeks' gestation. However, there were only marginal differences in the attributable risks, suggesting that the impact of elevated levels of antiphospholipid antibodies might be similar in early and later stages of pregnancy. None of the antiphospholipid antibodies was associated with pregnancy-induced hypertension. CONCLUSION: In this study, elevated levels of IgG anticardiolipin and IgG antiphosphatidylserine antibodies were markers of pregnancy loss, but an elevated level of anti-beta2-glycoprotein was not a strong predictor of fetal loss.

Abortion, Spontaneous↗
PubMed1998

Acute valproate ingestion induces symptomatic methemoglobinemia.

A wide variety of clinical outcomes have been described after acute valproate ingestion. We report for the first time the development of symptomatic methemoglobinemia after an acute ingestion of divalproex sodium (Depakote), resulting in serum concentrations 10 times greater than the therapeutic range. The methemoglobinemia was readily reversed with the administration of methylene blue. Valproate elimination was enhanced by the continuous infusion of activated charcoal. The patient recovered without permanent sequelae.

Acute Disease↗
PubMed1997

Antiphospholipid antibodies in healthy pregnant women.

This article discusses the prevalence and clinical significance of antiphospholipid antibodies (aPL) in the normal, healthy pregnant population. Although an increased risk for adverse fetal outcome has been shown in a small subset of this population, most pregnancies in aPL-positive mothers have successful outcomes. We review the variations in aPL levels during pregnancy and consider screening strategies and therapeutic interventions in healthy aPL-positive pregnant women.

Antibodies, Antiphospholipid↗
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↗