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J Johnstone

Publications and source records attributed to J Johnstone.

At least 19 recordsLinked to original sources

Clinical database development: characterization of EEG phenotypes.

We propose development of evidence-based methods to guide clinical intervention in neurobehavioral syndromes based on categorization of individuals using both behavioral measures and quantification of the EEG (qEEG). Review of a large number of clinical EEG and qEEG studies suggests that it is plausible to identify a limited set of individual profiles that characterize the majority of the population. Statistical analysis has already been used to document "clusters" of qEEG features seen in populations of psychiatric patients. These clusters are considered here as intermediate phenotypes, based on genetics, and are reliable indices of brain function, not isomorphic with DSM categories, and carry implications for therapeutic intervention. We call for statistical analysis methods to be applied to a broad clinical database of individuals diagnosed with neurobehavioral disorders in order to empirically define clusters of individuals who may be responsive to specific neurophysiologically based treatment interventions, namely administration of psychoactive medication and/or EEG neurofeedback. A tentative set of qEEG profiles is proposed based on clinical observation and experience. Implication for intervention with medication and neurofeedback for individuals with these neurophysiological profiles and specific qEEG patterns is presented.

Databases, Factual↗

Measurement of the systemic inflammatory response predicts cancer-specific and non-cancer survival in patients with cancer.

The assessment of prognosis in patients with advanced cancer remains problematical. The value of C-reactive protein concentration in this context has not been clearly defined. Patients with a diagnosis of colorectal (n = 182), gastric (n = 87), breast (n = 99), or bronchogenic (n = 404) cancer and who had measurements of C-reactive protein and albumin were identified. Median survival, from the time of sampling, ranged from 478 days in the colorectal cancer patients to 60 days in patients with bronchogenic cancer. On univariate analysis, there was, in each tumor type, a significant relationship between the duration of survival and both log10 C-reactive protein and albumin concentrations (P < or = 0.0002). On multivariate analysis, in each tumor type, log10 C-reactive protein remained a significant independent predictor of survival (P < or = 0.0002). When all four groups of cancer patients were analyzed (n = 772), the hazard ratio for a 10-fold increase in C-reactive protein concentration in cancer-specific survival was 2.21 (95% confidence interval = 1.92-2.56, P < 0.0001) and the corresponding hazard ratio for non-cancer survival was 5.48 (95% confidence interval = 3.55-8.46, P < 0.0001). The results of the present study indicate that in advanced cancer patients the presence of a systemic inflammatory response and the magnitude of that response predict the duration of cancer-specific and non-cancer survival.

Adult↗

The regulation of leptin gene expression in the C6 glioblastoma cell line.

The hormone leptin is implicated in the regulation of appetite and body weight in rodents, primates and humans. We reported that the leptin gene (ob) is expressed in the brain, but the factors which control ob expression in the central nervous system are not known. We previously showed that brain-derived rat C6 glioblastoma cells express ob mRNA and protein. In the present study we examined the regulation of ob expression in C6 cells. Leptin and leptin receptor immunoreactivity was detected in C6 cells, suggesting a possible autocrine role for leptin. The identity of the leptin immunoreactivity (OB-ir) in C6 cells was confirmed by immunoprecipitation and Western blotting using two leptin specific polyclonal antibodies. Using RT-PCR analysis a product of the expected size for the short, but not the long, leptin receptor isoform was detected in C6 cells. Cells were maintained in serum-free (SF) media for 0-24 h in the presence of various regulators of leptin expression. Leptin mRNA levels were significantly higher in cells treated with dbcAMP (1 mM), IGF 1 (100 ng/ml) or insulin (5 microg/ml) compared to SF controls. In contrast, corticosterone (10(-7)M) reduced leptin mRNA. In the presence of dbcAMP, C6 cells undergo a dramatic alteration in morphology which is coincident with an apparent increase in the number of leptin-ir nuclei and an increase in leptin immunoreactivity. In contrast to C6 cells, glucocorticoids are reported to increase leptin levels in adipocytes/adipose tissue, while increases in intracellular cAMP levels are reported to reduce leptin levels. Overall, our in vitro data suggest that the regulation of leptin gene expression in C6 glioblastoma cells is different from that in adipocytes.

Animals↗

Relation of genetic polymorphisms of apolipoprotein E, angiotensin converting enzyme, apolipoprotein B-100, and glycoprotein IIIa and early-onset coronary heart disease.

OBJECTIVE: Apolipoprotein E (APOE) E4, apolipoprotein B-100 (APOB) Q3611 allele, the angiotensin converting enzyme (ACE) deletion (D) allele and glycoprotein IIIa (GP3A) P33 mutant allele are reported to predispose to early-onset coronary heart disease (CHD). These associations were not all confirmed in more recent studies. To determine the impact of these alleles on CHD, we examined the prevalence of these mutations in patients presenting with early-onset CHD and compared them to those manifesting CHD later in life. The delayed-onset was considered a sign of longevity and would serve as a comparative group to assess prevalence of the biochemical and genetic risk factors. METHODS: 300 patients with a history of myocardial infarction or angina pectoris and angiographically documented CHD were studied. Patients were divided into two groups: group 1 (G1 = 150 patients) presenting with these findings under the age of 50 years; while group 2 (G2 = 150 patients) were patients presenting for the first time over the age of 65 years. Prevalence of the alleles of APOE, APOB, ACE and GP3A was assessed by molecular analysis. An association of any of these genotypes with early onset CHD could lead to a higher prevalence in the younger age group. RESULTS AND CONCLUSIONS: None of the suspected alleles namely APOB Q3611 [G1: 10.7% vs. G2: 9.0%, p = 0.57], ACE D (G1: 52.0% vs. G2: 49.7%, p = 0.57), or the GP3A P33 (G1: 17.3% vs. G2: 15.7%; p = 0.58) showed any significant difference between the two groups. Subjects with APOE E4 were more frequent in the younger age group (G1: 18.3% vs. G2: 13.7%; p = 0.047), while APOE E2 was more frequent in G2 (G2: 10.0% vs. G1: 2.7%; p = 0.0002). Multivariate analysis showed an odds ratio of APOE E2 allele in G1 of 0.27 with a confidence interval of 0.10-0.73.

Adult↗

Effect of ketorolac and low-molecular-weight heparin individually and in combination on haemostasis.

Low-molecular-weight heparins, when used in surgical patients for thromboprophylaxis, may be used concurrently with ketorolac, a non-steroidal anti-inflammatory drug that is used for analgesia. Because these two agents can influence the haemostatic system, it is important to identify any such effect. The haemostatic interaction between dalteparin and ketorolac was assessed in a double-blind, placebo-controlled, randomized, crossover study of healthy male volunteers each given all four combinations of ketorolac/placebo and dalteparin/placebo. The effect of ketorolac and dalteparin on haemostasis was assessed by measuring in-vitro platelet aggregation, anti-factor-Xa, activated partial thromboplastin times and skin bleeding time. The results were analysed for evidence of an interaction between ketorolac and dalteparin. Ketorolac inhibited platelet aggregation in whole blood and platelet-rich plasma. The administration of dalteparin led to a significant increase in levels of anti-factor-Xa and a significant prolongation in the activated partial thromboplastin time, although it remained within the range of the normal population. There was no evidence of any interaction between ketorolac and dalteparin with regard to platelet aggregation, anti-factor-Xa activity or activated partial thromboplastin time. The administration of ketorolac significantly prolonged the skin bleeding time. There was a significant interaction between ketorolac and dalteparin to prolong the bleeding time, although dalteparin alone had no effect on bleeding time. There was an interaction between ketorolac and dalteparin, which affected bleeding times. Such an interaction raises the possibility of haemorrhagic complications developing perioperatively when these agents are used concomitantly. Further studies are required to examine the clinical importance of this interaction.

Adolescent↗

Role of an improvement in acid-base status and nutrition in CAPD patients.

Short-term correction of metabolic acidosis in normal and uremic subjects has been shown to decrease protein degradation, but the long-term effects of better correction of acidosis on nutrition in ESRF are unknown. The aim of this study was to assess the possible benefits, in the nutritional state and morbidity, of improved correction of acidosis in the first year of treatment with continuous ambulatory peritoneal dialysis (CAPD). Two hundred consecutive new CAPD patients were randomized, in a single-blind fashion, to receive a high (HA; lactate 40 mmol/liter) or low (LA; lactate 35 mmol/liter) alkali dialysate for one year. Calcium carbonate and sodium bicarbonate were also used to correct acidosis in the HA group. At one year, the venous serum bicarbonate and arterial pH were 7.44 +/- 0.004 and 27.2 +/- 0.3 mmol/liter in the HA group, and 23.0 +/- 0.3 mmol/liter and 7.4 +/- 0.004 in the LA group (P < 0.001). Dialysis dose, at one year or at the point of leaving the study (HA 8.0 +/- 0.1 liters/day vs. LA 8.5 +/- 0.3 liters/day) was not significantly different (P = 0.18). At one year, the increase in body weight in the HA group (6.1 +/- 0.66 kg) was higher than in the LA group (3.71 +/- 0.56 kg, P < 0.05). The increase in midarm circumference in the HA patients (1.26 +/- 0.16 cm) was significantly higher than the increase in the LA patients (0.61 +/- 0.16 cm, P < 0.05). The increase in triceps skinfold thickness were not significantly different (HA 2.5 +/- 0.41 mm vs. LA 1.24 +/- 0.38 mm, P = 0.1). Serum albumin was 37.8 +/- 0.4 g/dl at one year in the HA group, and 38.2 +/- 0.5 g/dl in the LA group (NS). Dietary protein intake at one year (HA 0.9 +/- 0.2 g/kg/day vs. LA 1.0 +/- 0.1 g/kg/day) was not significantly different. There were fewer hospital admissions in the HA group (1.13 +/- 0.16 per patient per year) compared to the LA group (1.71 +/- 0.22 per patient per year, P < 0.05). The HA patients spent less days in hospital per year than the LA patients (16.4 +/- 1.4 days/year vs. 21.2 +/- 1.9 days/year; P < 0.05). It is concluded that better correction of metabolic acidosis leads to greater increases in body weight and midarm circumference, but not triceps skinfold thickness, in the first year of CAPD. The improvement in morbidity, in terms of number of admissions and days in hospital per year, may be associated with the improvement in nutritional state.

Acid-Base Equilibrium↗

Autoerotic asphyxia: a case report.

Autoerotic asphyxia is the induction of a state of oxygen deficiency to enhance sexual excitement and orgasm. It has been practiced for centuries, and there are many reports of fatalities. The authors report a case of a living participant that shows a number of characteristics different from those of fatalities. The case study also raises doubt about the conventional view that participants have no wish to die. We feel that further case studies of living participants will lead to a greater understanding of the practice and will facilitate treatment.

Adult↗

Manifestations of coronary atherosclerosis in young trauma victims--an autopsy study.

OBJECTIVES: The aim of this study was to look at the prevalence of coronary atherosclerosis, its severity and site of involvement in patients < 35 years old who died from noncardiac trauma. BACKGROUND: Autopsies performed on casualties of the Korean War revealed coronary artery involvement in 77.3% of the hearts studied, and data after the Vietnam War noted the presence of atherosclerosis in 45% of casualties with severe disease in 5%, suggesting a decline in the prevalence of coronary atherosclerosis in young men. METHODS: One hundred eleven victims of noncardiac trauma (86.4% white with a mean age of 26 +/- 6 years) underwent pathologic examination of their coronary arteries to estimate the presence and severity of coronary atherosclerosis grossly, microscopically and through computerized planimetry. Identified segments of the coronary arteries were sectioned at 3-mm intervals, stained with special stains and after microscopic examination transferred to videotape and digitized to allow estimation of the percent compromise in the lumen area by atherosclerotic plaque. RESULTS: Signs of coronary atherosclerosis were seen in 78.3% of the total study group, with > 50% narrowing in 20.7% and > 75% narrowing in 9%. No demographic or anatomic features separated the groups with less or more severe involvement of their coronary arteries. Proximal involvement was more common except in the right coronary artery, which was as frequently involved distally. CONCLUSIONS: The overall prevalence of coronary atherosclerosis in a young, predominantly male study group was comparable with that noted after the Korean War. Left main or significant two- and three-vessel involvement was noted in 20% of the group studied and emphasizes the need for aggressive risk factor modification in this group.

Adolescent↗

Suppression of non-esterified fatty acids and triacylglycerol in experimental animals by the adenosine analogue GR79236.

1. This is the first description of the metabolic activity of a novel adenosine A1-receptor agonist, GR79236. GR79236 inhibited catecholamine-induced lipolysis in human, rat and dog isolated adipocytes. 2. Oral administration of GR79236 (0.1-10 mg/kg) to fed rats induced minimal changes in the plasma concentration of non-esterified fatty acids and in the blood concentrations of glucose and lactate. 3. Intravenous infusion of GR79236 to fasted pithed rats, or oral administration of GR79236 to fasted conscious rats and dogs, produced time- and dose-dependent decreases in the plasma non-esterified fatty acid concentration. In the fasted rats, doses of GR79236 that lowered plasma levels of non-esterified fatty acids also produced hypotriglyceridaemia and anti-ketotic effects. 4. Only in the pithed rats were acute effects on the plasma glucose and lactate concentrations observed. Hypoglycaemia and hyperlactataemia occurred over the dose range studied (1 x 10(-11)-1 x 10(-8) mol min-1 kg-1). 5. This profile of activity suggests that compounds such as GR79236 might be agents which can be used to define the role of excessive lipolysis in experimental (and human) pathophysiology.

Adenosine↗

Production and characterization of monoclonal antibodies to the carboxyl-terminal heptapeptide of endothelin-1.

Two cell lines, RR5.ET-1 and RR1.ET-1, that produce monoclonal antibodies specific for the carboxyl-terminal heptapeptide of endothelin-1 (ET-1) have been cloned and stabilized. An RIA was developed to facilitate the evaluation and characterization of these monoclonal antibodies. The affinity constant of each MAb for ET-1, as determined by Scatchard analysis, was 5.74 x 10(8) M-1 for RR5.ET-1 and 4.15 x 10(7) M-1 for RR1.ET-1. The antibodies reacted specifically with the carboxyl-terminus (ET15-21) and did not cross-react with the amino-terminal amino acids (ET1-16). As expected, the antibodies cross-reacted with endothelin-2 (ET-2) and endothelin-3 (ET-3), and to a lesser extent, with the closely related sarafotoxins. Both MAbs retained about 55% reactivity with the ET-1 terminal sequence of Asp-Ile-Ile-Trp (ET18-21) but had no reactivity with the ET sequence His-Leu-Asp-Ile-Ile-Trp-Val-Asn (ET16-23) nor with Big ET-1 (ET1-39). These data strongly suggest that the terminal four amino acids of ET-1 are included in the MAb binding site. More importantly, the terminal Trp21 must be free, not linked to Val22 to retain reactivity with either of the MAbs.

Amino Acid Sequence↗

The effect of exercise-induced myocardial ischemia on postischemic left ventricular diastolic filling.

To determine whether exercise-induced ischemia impairs left ventricular diastolic filling in the postischemic period in humans, 101 men (mean age 57 +/- 10 years) were studied before and 2 h after a symptom-limited thallium-201 tomographic treadmill with pulsed Doppler echocardiography of mitral valve inflow. In the postischemic period 2 h after exercise, diastolic filling was significantly impaired in the ischemia group (reversible thallium defect; n = 24) as reflected by a decrease in the peak early filling velocity (44.5 +/- 10.1 to 39.9 +/- 9.9 cm/s, p less than 0.01), peak early to atrial filling velocity ratio (0.91 +/- 0.27 to 0.76 +/- 0.25, p less than 0.001), and deceleration rate of early filling (281 +/- 104 to 245 +/- 86 cm/s2, p less than 0.01). Similar alterations in the postischemic period occurred in the myocardial infarction-ischemia group (partially reversible defect; n = 28) as seen by a decrease in the peak early filling velocity (47.6 +/- 11.6 to 41.8 +/- 12.0 cm/s, p less than 0.001), peak early to atrial filling velocity ratio (0.84 +/- 0.21 to 0.68 +/- 0.18, p less than 0.001), and early time-velocity integral (7.06 +/- 1.78 to 5.64 +/- 2.07 cm, p less than 0.001). In the control group (no defects; n = 33) and myocardial infarction group (fixed defect; n = 16), diastolic filling was unchanged in the postexercise period. Heart rate and blood pressure were unchanged post-exercise in all groups. Exercise-induced ischemia impairs diastolic filling in the postischemic period in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Circulation↗

EEG spectra in dyslexic and normal readers during oral and silent reading.

EEGs of extensively screened dyslexics and normal readers were recorded while they read easy and difficult texts silently and orally, and during two other verbal tasks which also differed in overt speaking but had no reading component: narrative speaking and listening to a story. Mid-temporal, central and parietal leads were referenced to linked ears and to Cz. Large differences between tasks and between groups were found. With the linked ears reference, power was higher in all bands in oral reading than in silent reading, with the largest change occurring in the temporal leads. In the theta and low beta bands the difference between oral and silent reading was greater for controls than for dyslexics. These effects were not accounted for by differences in reading speed or in difficulty. Similar results were found in two cohorts of subjects. The difference between groups in theta was found only in the reading tasks. In contrast, the group difference in low beta was also found in the change from listening to speaking. This implies that the oral-silent group difference in theta is related to some aspect of the reading tasks other than the presence or absence of overt speaking, and that the low beta group difference is related to some aspect of overt speaking rather than to reading per se. With the Cz reference no group differences were found. It is suggested that the groups differ in the reading strategies they use, and the degree to which they shift strategy between the silent and oral tasks. We hypothesize that these cognitive differences are reflected in the theta activity from the temporal lobe. While there were many differences between the tasks in alpha power and asymmetry, no group differences involving alpha were found.

Adolescent↗

Prospects for national health care in the United States.

This paper provides an overview of both the current health care crisis in the United States and various reform proposals (some based on Canadian and British models) being considered at the federal and state levels. The proposals discussed fall into three categories--multiple payer national health insurance programs, one payer national health insurance programs, and a national health service program. The authors review four important criteria (cost, quality, access, and equity) that must be considered in evaluating the proposals for reform. Information is provided to assist health care professionals in understanding the various national health care proposals, applying evaluative criteria to these proposals, and advocating for needed changes.

Canada↗

Second-trimester placental biopsy for rapid fetal karyotyping.

Since January 1988 the technique of first-trimester chorionic villus sampling (placental biopsy) has been extended to include cases in the second trimester. To date, 40 procedures have been performed. The main indication for the late chorionic villus sampling was a low serum alpha-fetoprotein value in association with an increased risk for Down syndrome (n = 28), abnormal ultrasonographic finding (n = 7), and failed amniotic cell culture (n = 3). Successful karyotype results were achieved in all but two cases. Most results were obtained within 48 hours with direct cytogenetic techniques. No cases of mosaicism were found. The highest yield of abnormal karyotypes was obtained from the cases with abnormal ultrasonographic findings (one trisomy 21, two 45,X). One case of trisomy 21 was identified in the 28 cases of low serum alpha-fetoprotein. No spontaneous losses have occurred. The technique is easy to learn, does not differ from first-trimester procedures, and may have a lower complication rate than cordocentesis. The reporting of cases to the CVS Newsletter should help evaluate late chorionic villus sampling as another method for rapid fetal karyotyping.

Adult↗

The transfer of ketorolac tromethamine from maternal to foetal blood.

Thirty two women who were participating in an efficacy study comparing 10 mg ketorolac with 50 mg or 100 mg of pethidine in the relief of labour pain, underwent sampling of vein blood, for determination of plasma ketorolac concentrations. The sample was withdrawn at delivery and a sample of umbilical cord blood was withdrawn at the same time. The ratio of ketorolac concentrations in the cord blood sample: the maternal venous sample were calculated and plotted against the time elapsed between drug administration and sampling. Samples for one patient, withdrawn 24 min after dosing, had ketorolac concentrations below the quantification limit. The ratios in the remaining patients were all low and showed a tendency to increase with time. The mean ratio was 0.116 with a range of 0.04 in 2 patients, at 43 min and 1 h 6 min, to 0.25 at 6 h 34 min.

Adult↗

EEG alpha asymmetry in dyslexics during speaking and block design tasks.

Lateral specialization for speech and spatial construction was investigated in a highly screened group of dyslexic and normal-reading boys, age 9-13, by examining the extent to which their EEG alpha asymmetry changed from one task to the other. EEG was recorded from central, midtemporal, and parietal leads during several minutes of spontaneous narrative speech, and while the child constructed block designs. The dyslexics showed the same strongly task-dependent asymmetry as the normal readers, comparable to that observed in our adult populations. The observations were confirmed with a second independently chosen cohort of subjects. This result is discussed in terms of the constraints it places on models of dyslexia which invoke disorders of lateral specialization and hemisphere integration.

Adolescent↗