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Biomedical subjects

J A Lawson

Publications and source records attributed to J A Lawson.

At least 19 recordsLinked to original sources

The impact of epilepsy surgery on quality of life in children.

OBJECTIVE: To determine if epilepsy surgery is effective in improving the quality of life (QOL) of children with intractable seizures using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). METHODS: The authors conducted a prospective study of the families of 35 children with intractable epilepsy who underwent epilepsy surgery. Parents completed the QOLCE preoperatively and again 6 to 18 months after surgery. At both assessment dates parents indicated the severity of their child's seizures during the past 6 months and the frequency of their child's seizures during the past 4 weeks on Likert-type scales. Children were split into two groups according to surgery outcome: seizure free vs persistent seizures. Statistical analyses were conducted to determine if children rendered seizure free showed a greater improvement in QOL compared to those with persistent seizures postoperatively. RESULTS: Greater improvement in QOL was documented for children rendered seizure free vs children with persistent seizures. This was significant for the overall QOLCE QOL score and subscales assessing cognitive, social, emotional, behavioral, and physical domains of life. CONCLUSIONS: Epilepsy surgery improves the quality of life of children rendered seizure free. Families can be counseled preoperatively of the potential benefits of surgery beyond seizure reduction.

Adolescent↗

Respiratory response to endotoxin and dust predicts evidence of inflammatory response in volunteers in a swine barn.

BACKGROUND: It has been shown that exposure in intense exposure in swine barn facilities is associated with increased respiratory symptoms and reduction in pulmonary functions. This study investigated if systemic response could be predicted by FEV(1) response following swine barn exposure. METHODS: Naïve males were tested at baseline, low and high endotoxin and dust levels. Subjects were classified as "more responsive" (n = 9) or "less responsive" (n = 11) based on FEV(1) reduction following high endotoxin exposure. Health measures included pulmonary function testing, blood samples and nasal lavage. Environmental samples were collected from the barn. RESULTS: White blood cells and blood lymphocytes at low exposure were significantly greater in those who were "more responsive" compared to those who were "less responsive". There was a significant increase in blood lymphocytes, serum IL6, total nasal lavage cells and nasal IL8 at high exposure among "more responsive" subjects compared to "less responsive" subjects. CONCLUSIONS: Respiratory response to high-level endotoxin and dust exposure predicts evidence of inflammatory response throughout a range of endotoxin and dust exposures.

Adolescent↗

Outcome after occlusion of infrainguinal bypasses in the Dutch BOA Study: comparison of amputation rate in venous and prosthetic grafts.

OBJECTIVE: To compare the consequences of occlusion of infrainguinal venous and prosthetic grafts. METHODS: In total, 2690 patients were included in the Dutch BOA study, a multicenter randomised trial that compared the effectiveness of oral anticoagulants with aspirin in the prevention of infrainguinal bypass graft occlusion. Two thousand four hundred and four patients received a femoropopliteal or femorodistal bypass with a venous (64%) or prosthetic (36%) graft. The incidence of occlusion and amputation was calculated according to graft material and the incidence of amputation after occlusion was compared with Cox regression to adjust for differences in prognostic factors. RESULTS: The indication for operation was claudication in 51%, rest pain in 20% and tissue loss in 28% of patients. The mean follow up was 21 months. After venous bypass grafting 171 (15%) femoropopliteal and 96 (24%) femorodistal grafts occluded. After prosthetic bypass grafting 234 (30%) femoropopliteal and 25 (38%) femorodistal grafts occluded. Patients with occlusions in the venous group had more severe ischemia, less runoff vessels and were older than the patients with prosthetic grafts. In the venous occlusion group 54 (20%) amputations were performed compared to 42 (16%) in the prosthetic occlusion group; crude hazard ratio 1.17 (95% CI 0.78-1.75). After adjustment for above mentioned differences in patient characteristics the hazard ratio was 0.86 (95% CI 0.56-1.32). CONCLUSION: The need for amputation after occlusion is not influenced by graft material in infrainguinal bypass surgery.

Aged↗

Risk of major haemorrhage in patients after infrainguinal venous bypass surgery: therapeutic consequences? The Dutch BOA (Bypass Oral Anticoagulants or Aspirin) Study.

OBJECTIVES: The beneficial effect of oral anticoagulants after infrainguinal venous bypass surgery is compromised by bleeding complications. We developed a model to identify patients, treated with anticoagulation, at risk of major haemorrhage and estimated whether this complication could have been prevented if patients had received aspirin. DESIGN: Randomised clinical trial. METHODS: Data of patients who participated in the Dutch Bypass Oral Anticoagulation or Aspirin Study were reanalysed using Cox regression. After infrainguinal bypass surgery these patients were randomised to oral anticoagulants (n = 1326) or aspirin (n = 1324). RESULTS: Predictors of major haemorrhage for patients on oral anticoagulants were increased systolic blood pressure (> or = 140 mmHg, hazard ratio [HR] 1.62), age > or = 75 years (HR 2.77) and diabetes mellitus (HR 1.60). If the 345 patients in the highest risk quartile had received aspirin, major haemorrhages would have been reduced from 46 to 22, with no major changes in ischemic events and graft occlusions. In the subgroup with venous bypasses major haemorrhages would have been reduced from 27 to 13, at the cost of seven more ischemic events (mostly fatal) and 17 more graft occlusions. CONCLUSIONS: Treating patients at highest risk of major haemorrhage with aspirin instead of oral anticoagulants would have resulted in a reduction of non-fatal haemorrhages, but for venous bypasses this reduction was outweighed by an increase in ischemic events and graft occlusions. We still recommend treatment with oral anticoagulants after peripheral venous bypass surgery.

Administration, Oral↗

Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning?

Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg i.p.) effects of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA), isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand breaks were investigated to determine whether the oxidative effects of CCl4 would result in increased generation of these oxidation products. Plasma concentrations of MDA and isoprostanes (both measured by GC-MS) and urinary concentrations of isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both low-dose and high-dose CCl4-treated rats at more than one time point. The other urinary markers (MDA and 8-OHdG) showed significant elevations with treatment under three of the four conditions tested. It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential candidates for general biomarkers of oxidative stress. All other products were not changed by CCl4 or showed fewer significant effects.

8-Hydroxy-2'-Deoxyguanosine↗

Biomarkers of oxidative stress study III. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCl4 poisoning.

Plasma and urinary levels of malondialdehyde-like products (MDA) and isoprostanes were identified as markers of in vivo lipid peroxidation in an animal model of CCl4 poisoning. We sought to determine the extent to which the formation of these oxidation products is influenced by inhibition of the cyclooxygenase enzymes which catalytically generate proinflammatory lipid peroxidation products known as prostaglandins and thromboxane. In the present studies, after induction of oxidant stress in rats with CCl4, lipid peroxidation products measured in plasma and urine demonstrate that isoprostanes and MDA can be partially inhibited by cyclooxygenase inhibitors, albeit to different extents. The lowering of isoprostane and MDA formation, however, may not to due primarily to the diminution of catalytic generation of isoprostanes or MDA by the cyclooxygenases but, rather, may be the result of the suppression of nonenzymatic lipid peroxidation. This is suggested since 8,12-iso-iPF2alpha-VI is also reduced by indomethacin, yet, unlike other isoprostanes and MDA, it is not generated catalytically by the cyclooxygenase. Thus, although the two cyclooxygenase inhibitors we tested have statistically significant effects on the measurements of both isoprostanes and MDA in this study, the results provide evidence that these lipid-degradation products primarily constitute markers of oxidative stress.

Animals↗

Distinct clinicopathologic subtypes of cortical dysplasia of Taylor.

BACKGROUND: Two pathologic subtypes based on the presence or absence of balloon cells have been described in cortical dysplasia of Taylor (CDT). OBJECTIVE: To determine whether the pathologic subtype has any distinct clinical or MRI features that are relevant to management. METHODS: The histopathologic, clinical, and MRI features of 34 children with CDT who underwent epilepsy surgery at Miami Children's Hospital from 1990 to 2001 were investigated. RESULTS: Bizarre neuronal cytomegaly was the primary pathologic feature of 15 patients with the dysplasia-only subtype, and 19 cases showed additional characteristics including balloon cells and marked white matter abnormalities. Both groups presented with severe intractable epilepsy of very-early-onset, multiple daily seizures, cognitive disability, and focal neurologic deficits. The dysplasia-only subtype had higher rates of neonatal onset, hemiparesis, and severe mental retardation (p < 0.05). The MRI features of focal cortical thickening with associated cortical T2 signal change showed excellent sensitivity (94%) and reasonable specificity (73%) for the diagnosis of the balloon cell subtype. The overall surgical outcome was 59% seizure freedom at 2 years. CONCLUSIONS: Children with cortical dysplasia of Taylor type have in common a very-early-onset, severe epilepsy with neurologic co-morbidity. Patients with the non-balloon cell pathologic subtype have a more severe phenotype. A trend toward a better outcome in the balloon cell group suggests that preoperative identification of these subtypes may impact surgical planning.

Adolescent↗

Occupational asthma in newly employed workers in intensive swine confinement facilities.

Respiratory symptoms, reductions in pulmonary function and increased bronchial responsiveness have been described in exposed workers and in naïve volunteers exposed to intensive swine production facilities. Typically, this occurs in persons who have been employed for a long duration or in previously unexposed, naïve volunteers. The current authors describe four cases, all female, who developed acute onset of wheezing and cough suggestive of asthma within weeks of commencing full-time employment in intensive swine production facilities. None of the workers were aware of any previous asthma, allergies or hay fever. All four employees reported improvement of symptoms on cessation of work in the facilities and consequent withdrawal from exposure. However, when seen at the respiratory clinic, cases 1 and 3 continued to be either mildly symptomatic or were taking medications with continued borderline airways responsiveness, as measured by methacholine challenge test up to 4 and 5 months, respectively, following work cessation. Case 2 continued to have symptoms for > or =3 months after work cessation. Only case 1, however, was seen at repeated visits in the respiratory clinic. One worker participated in a work re-entry trial and experienced profound coughing and chest tightness within an hour of entry, after which, the trial had to be terminated. Provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20) measured 5 h later was lower than pre-trial PC20. No acute exposure event was recorded in the workers prior to the onset of symptoms. To the current authors' knowledge, this is the first report of occupational asthma occurring in newly employed full-time intensive swine production workers after a short-term exposure and should raise awareness that previously unexposed workers may be at risk of developing what would appear to be long-term asthma after relatively short-term exposure.

Adult↗

The health-related quality of life of childhood epilepsy syndromes.

OBJECTIVE: There is increasing awareness of the importance of assessing physical, psychological, social and behavioural well-being in chronic disease. The aim of this study was to examine the health-related quality of life (HRQoL) of children with common epilepsy syndromes and to explore if there are HRQoL differences between those syndromes. METHODS: Each child had their epilepsy syndrome defined according to the International League Against Epilepsy classification. Epilepsy syndromes included symptomatic frontal, temporal, parietal/occipital lobe and partial unlocalized epilepsy, and two idiopathic epilepsies, childhood absence epilepsy (CAE) and benign rolandic epilepsy (BRE). Seizure semiology and ictal/interictal electroencephalogram (EEG) were determined for symptomatic partial epilepsy syndromes by video-EEG monitoring. HRQoL was evaluated with an epilepsy-specific instrument, the Quality of Life in Childhood Epilepsy Questionnaire, and two generic instruments, the Child Health Questionnaire and Child Behavior Checklist. RESULTS: Children with symptomatic partial epilepsy syndromes were affected by epilepsy in a similar way and did not have unique HRQoL profiles. However, these children had significantly lower HRQoL scores compared to those with CAE or BRE. All children with epilepsy regardless of syndrome had a higher frequency of behavioural problems compared to normative data. CONCLUSION: These results indicate that children with epilepsy regardless of syndrome require evaluation of the psychosocial implications. There is a greater impact on HRQoL in symptomatic epilepsy compared to idiopathic epilepsy. Specific symptomatic partial syndromes did not differ in the degree they affect HRQoL. These findings have important implications for clinicians caring for children with epilepsy.

Adolescent↗

Clinical, EEG, and quantitative MRI differences in pediatric frontal and temporal lobe epilepsy.

OBJECTIVE: To examine the clinical, electrographic, and quantitative MRI differences between frontal lobe (FLE) and mesial temporal lobe epilepsy (MTLE) in children. METHODS: The population included children who underwent video-EEG monitoring between 1995 and 2000 who were classified as either FLE (n = 39) or MTLE (n = 17) according to the criteria of the International League Against Epilepsy. Clinical, EEG, and quantitative MRI data (including frontal cortical volumes) were compared between the two syndromes and a control group (n = 42). RESULTS: In FLE, seizures were significantly briefer, more frequent, and predominantly from sleep, and had differing motor characteristics. The rates of bilateral epileptiform interictal and ictal EEG abnormalities were significantly higher in FLE. A nonlesional MRI was significantly more common in FLE. Mean frontal cortical volume in FLE was significantly lower than MTLE and controls. Seizure freedom after surgery was lower in FLE. CONCLUSIONS: The clinical syndrome of FLE is clearly distinct from MTLE. The etiology of this disorder is unknown in the majority of cases despite extensive investigation. Because of a lack of a clearly defined etiology and frequent nonlateralizing EEG changes, few of these children are considered optimal surgical candidates. The demonstration of bilateral frontal cortical volume loss and bilateral EEG abnormalities suggests that FLE is a bilateral disease in a high proportion of patients. The outcome in those patients who were deemed surgical candidates was significantly worse than the MTLE cases.

Adolescent↗

The influence of hyperhomocysteinemia on graft patency after infrainguinal bypass surgery in the Dutch BOA Study.

OBJECTIVE: Hyperhomocysteinemia has been identified as a risk factor for (cardio)vascular disease. Whether hyperhomocysteinemia contributes to graft failure after peripheral bypass surgery remains unclear. The present study evaluated the influence of hyperhomocysteinemia on graft patency after infrainguinal bypass surgery. DESIGN: The present study was designed as a nested case-control study. METHOD: In this study (nested in the Dutch Bypass Oral anticoagulants or Aspirin Study), 150 patients with graft occlusion were each matched with two randomly selected controls with patent grafts (N = 299) from the same trial. Venous blood samples were drawn from cases and controls, and total plasma homocysteine (tHcy) was determined. Mean serum homocysteine levels and the presence of hyperhomocysteinemia (>95th percentile in healthy individuals) were compared between cases and controls. RESULTS: No significant differences were found between serum levels of homocysteine in patients with and without graft occlusion. The mean plasma homocysteine levels were 14.4 micromol/L and 14.9 micromol/L in the case and control groups, respectively. The resulting mean difference was -0.4 (95% confidence interval [CI], -1.8-0.9). The odds ratio of hyperhomocysteinemia was 0.81 (95% CI, 0.49-1.33). Adjustment for risk factors of graft occlusion did not change these results. CONCLUSIONS: Postoperative raised serum levels of homocysteine proved not to be a risk factor for graft occlusion after infrainguinal bypass grafting.

Aged↗

Effects of vitamin E on lipid peroxidation in healthy persons.

CONTEXT: Oxidative stress may play a role in the development or exacerbation of many common diseases. However, results of prospective controlled trials of the effects of antioxidants such as vitamin E are contradictory. OBJECTIVE: To assess the effects of supplemental vitamin E on lipid peroxidation in vivo in healthy adults. DESIGN: Randomized, double-blind, placebo-controlled trial conducted March 1999 to June 2000. SETTING: A general clinical research center in a tertiary referral academic medical center. PARTICIPANTS: Thirty healthy men and women aged 18 to 60 years. INTERVENTIONS: Participants were randomly assigned to receive placebo or alpha-tocopherol dosages of 200, 400, 800, 1200, or 2000 IU/d for 8 weeks (n = 5 in each group), followed by an 8-week washout period. MAIN OUTCOME MEASURES: Three indices of lipid peroxidation, urinary 4-hydroxynonenal (4-HNE) and 2 isoprostanes, iPF(2alpha)-III and iPF(2alpha)-VI, measured by gas chromatography/mass spectrometry and compared among the 6 groups at baseline, 2, 4, 6, and 8 weeks, and 1, 3, and 8 weeks after discontinuation. RESULTS: Circulating vitamin E levels increased in a dose-dependent manner during the study. No significant effect of vitamin E on levels of urinary 4-HNE or either isoprostane was observed. Mean (SEM) baseline vs week 8 levels of iPF(2alpha)-III were 154 (20.1) vs 168 (22.3) pg/mg of creatinine for subjects taking placebo; 165 (19.6) vs 234 (30.1) pg/mg for those taking 200 IU/d of vitamin E; and 195 (26.7) vs 213 (40.6) pg/mg for subjects taking 2000 IU/d. Corresponding iPF(2alpha)-VI levels were 1.43 (0.6) vs 1.62 (0.4) ng/mg of creatinine for subjects taking placebo; 1.64 (0.3) vs 1.24 (0.8) ng/mg for those taking 200 IU/d of vitamin E; and 1.83 (0.3) vs 1.94 (0.9) ng/mg for those taking 2000 IU/d. Baseline vs week 8 levels of 4-HNE were 0.5 (0.04) vs 0.4 (0.05) ng/mg of creatinine for subjects taking placebo; 0.4 (0.06) vs 0.5 (0.02) ng/mg with 200 IU/d of vitamin E; and 0.2 (0.02) vs 0.2 (0.1) ng/mg with 2000 IU/d. CONCLUSIONS: Our results question the rationale for vitamin E supplementation in healthy individuals. Specific quantitative indices of oxidative stress in vivo should be considered as entry criteria and for dose selection in clinical trials of antioxidant drugs and vitamins in human disease.

Adult↗

The isoprostanes in biology and medicine.

Isoprostanes are a new class of lipids, isomers of the conventional enzymatically derived prostaglandins, which are produced in vivo primarily by a free radical-catalyzed peroxidation of polyunsaturated fatty acids. F2-isoprostanes, isomers of the enzyme-derived prostaglandin F2alpha, are the most studied species, but analogous isomers of other prostaglandins and leukotrienes have been described. Because of their mechanism of formation, specific structural features that distinguish them from other free radical-generated products and chemical stability, they can provide a reliable index for the oxidant component of several diseases in vivo. Consistent data suggest that formation of F2-isoprostanes is altered in a variety of clinical settings putatively associated with oxidant stress. Moreover, measurement of F2-isoprostanes might provide a sensitive biochemical basis for dose-selection in studies of natural and synthetic antioxidants. Finally, some F2-isoprostanes possess potent biological activities in vitro and in vivo, suggesting that they may also act as mediators of the cellular effects of oxidative stress.

Dinoprost↗

Prevalence and prognostic significance of malnutrition in chronic renal insufficiency.

OBJECTIVE: Malnutrition is present in a significant proportion of patients commencing dialysis. However, the prevalence and prognostic significance of malnutrition within the chronic renal insufficiency (CRI) population before the initiation of dialysis is poorly characterized. The aim of this study was to determine the prevalence and prognostic significance of malnutrition in an unselected group of patients with CRI. DESIGN: Cohort analytic study. SETTING: Ambulatory care practice of a university teaching hospital. PATIENTS: Fifty patients with CRI (serum creatinine concentration > or = 1.7 mg/dL) were enrolled. Patients with a recent acute illness, nephrotic syndrome, intercurrent steroid therapy, gastrointestinal disease, or other severe organ failure that may have independently influenced nutritional status were excluded. INTERVENTION: At baseline, patients had a nutritional assessment consisting of subjective global assessment (SGA), measurement of body mass index (BMI), midarm circumference (MAC), serum albumin concentration, total lymphocyte count, and single frequency bioelectrical impedance analysis. Patients received standard medical care and were followed prospectively at quarterly intervals for 12 months. RESULTS: At baseline assessment, 28% of patients had evidence of malnutrition by SGA criteria. The malnourished group of patients had a significantly lower creatinine clearance (18.9 +/- 9.8 v 36.5 +/- 14.0 mL/min/1.73 m(2), mean +/- SD, P <.001), glomerular filtration rate (20.7 +/- 10.9 v 28.5 +/- 12.5 mL/min/1.73 m(2), P =.04), BMI (22.7 +/- 2.9 v 29.0 +/- 5.0 kg/m(2)), and MAC (24.3 +/- 4.9 v 30.7 +/- 4.8 cm, P <.001), but there were no differences in serum albumin concentration or total lymphocyte count between the groups. At the 12-month follow-up, there was significantly increased mortality (21% v 3%, P =.04), composite endpoint of death or dialysis (50% v 11%, P =.02), and likelihood of acute hospitalization (78% v 23%, P =.001) in the malnourished group. A significant association was observed between baseline nutritional status and subsequent admission to hospital and baseline glomerular filtration rate and progression to end-stage renal failure. CONCLUSION: These data suggest that SGA provides a useful means of assessing nutritional status and is helpful in identifying patients with increased risk of morbidity and mortality in the setting of CRI.

Aged↗

The health-related quality of life of children with refractory epilepsy: a comparison of those with and without intellectual disability.

PURPOSE: To determine whether refractory epilepsy affects the health-related quality of life (HRQOL) of children with or without intellectual disability (ID), and if the presence of ID independently compromises HRQOL in children with refractory epilepsy. METHODS: Subjects were parents of children with refractory epilepsy, whose syndrome had been defined using ILAE (International League Against Epilepsy) criteria and video-EEG monitoring. Children had the presence or absence of ID determined by formal neuropsychological or educational assessment. The relative effect of epilepsy on the two intellectual ability groups was determined using relevant clinical variables. Parents completed a valid epilepsy-specific HRQOL questionnaire for children, the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE), and, depending on intellectual ability level, the Child Behaviour Checklist or Developmental Behaviour Checklist. RESULTS: Both intellectually normal children with epilepsy and children with epilepsy and ID were more likely to have psychosocial problems compared with their respective intellectual ability reference populations. The results also revealed that children with ID had reduced HRQOL compared with intellectually normal children; a result independent of epilepsy. Analysis of the relationship between epilepsy variables and HRQOL revealed that the QOLCE was the most sensitive in detecting variation in age at onset, seizure frequency, and medications taken. CONCLUSIONS: The HRQOL of children with refractory epilepsy is greatly affected, regardless of intellectual ability level. The presence of ID in children with epilepsy independently depresses HRQOL outcomes. Compared with two generic HRQOL measures, the QOLCE was the most sensitive measure to variation in epilepsy variables.

Adolescent↗

No evidence for lipid peroxidation in severe preeclampsia.

OBJECTIVE: This study was undertaken to address the role of oxidative stress in preeclampsia. STUDY DESIGN: We measured urinary 8,12-iso-iPF(2alpha)-VI, a chemically stable, free-radical catalyzed product, in a case control study of severe preeclampsia nested within the trial of Calcium for Preeclampsia Prevention. Cases included 29 women who developed severe preeclampsia and from whom urine had been obtained 10 to 20 weeks before the diagnosis of preeclampsia, 3 to 9 weeks before, and 1 day before through delivery. Controls did not develop hypertension or proteinuria and were matched to cases by center, gestational age at each of 3 corresponding urine collections, and date of enrollment. RESULTS: Urinary 8,12-iso -iPF(2alpha)-VI did not differ significantly between cases and controls before or at diagnosis of preeclampsia, nor did it vary with gestational age. CONCLUSIONS: These results call into question the importance of oxidative stress in the disease and the biochemical rationale for clinical trials of antioxidants to prevent and treat preeclampsia.

Adult↗