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Biomedical subjects

C A Jackson

Publications and source records attributed to C A Jackson.

At least 55 records · Page 3Linked to original sources

Misclassification of diabetic subjects may account for the increased vascular risk of impaired glucose tolerance: the Islington Diabetes Survey.

We have studied the associations of macrovascular disease and hypertension with impaired glucose tolerance in a recall sample of 223 subjects selected from a population aged greater than or equal to 40 years who had been screened for diabetes using two separate glucose tolerance tests. Blood pressure was higher in subjects with diabetes, but not in those with impaired glucose tolerance, than in normals. Coronary heart disease, based on ECG criteria and history, was more frequent both in subjects with impaired glucose tolerance (odds ratio 1.94, 95% CI 1.02-3.69) and those with diabetes (odds ratio 3.88, 95% CI 1.33-11.97) than in normals, but the excess in the impaired glucose tolerance group was reduced, and was no longer significant, when adjusted for other variables (odds ratio 1.29, 95% CI 0.62-2.66). Peripheral vascular disease was more frequent in subjects with diabetes, but not in those with impaired glucose tolerance. When the subjects with impaired glucose tolerance on a single test were reclassified according to the results of a separate glucose tolerance test, the prevalence of coronary heart disease increased significantly with increasing degrees of glucose intolerance. Subjects with impaired glucose tolerance on both tests had an adjusted odds ratio of coronary heart disease of 0.90 (95% CI 0.42-1.94) compared with normal subjects. The excess of macrovascular disease in subjects with impaired glucose tolerance may result, at least in part, from the admixture of 'false negative diabetics' in that class.

Adult↗

Chloroquine inhibition of cholera toxin.

Cholera toxin (CT) stimulated adenylate cyclase and a phospholipase which elevated cellular levels of 3',5'-cyclic adenosine monophosphate (cAMP) and arachidonic acid (AA). The AA was quickly converted to prostaglandins (PGs) via the cyclo-oxygenase pathway. Chloroquine exerted minimal inhibition of cAMP levels in CT-treated cells, although CT-induced release of [3H]AA and PGs was blocked completely when the drug was added in concentrations as low as 0.1 mM (50 micrograms/ml). Inhibition of [3H]AA release was complete when chloroquine was added before or within 30 min after CT. The capacity of chloroquine to inhibit either phospholipase C (PLC) or phospholipase A2 (PLA2) could explain the antisecretory activity of this drug.

Animals↗

Temporoparietal cortex in aphasia. Evidence from positron emission tomography.

Forty-four aphasic patients were examined with (F18)-fluorodeoxyglucose positron emission tomography in a resting state to determine whether consistent glucose metabolic abnormalities were present. Ninety-seven percent of subjects showed metabolic abnormalities in the angular gyrus, 89% in the supramarginal gyrus, and 87% in the lateral and transverse superior temporal gyrus. Pearson product moment correlations were calculated between regional metabolic measures and performance on the Western Aphasia Battery. No significant correlations were found between the Western Aphasia Battery scores and right hemisphere metabolic measures. Most left hemisphere regions correlated with more than one score from the Western Aphasia Battery. Temporal but not frontal regions had significant correlations to the comprehension score. The left temporoparietal region was consistently affected in these subjects, suggesting that common features in the aphasias were caused by left temporoparietal dysfunction, while behavioral differences resulted from (1) the extent of temporoparietal changes, and (2) dysfunction elsewhere in the brain, particularly the left frontal and subcortical areas.

Adult↗

Unexplained variability of glycated haemoglobin in non-diabetic subjects not related to glycaemia.

We have studied levels of glycated haemoglobin in a sample of 223 people aged over 40 years without known diabetes mellitus screened in a community study. Each had a glucose tolerance test and glycated haemoglobin measured by four methods - agar gel electrophoresis with and without removal of Schiff base, affinity chromatography and isoelectric focusing. The correlation coefficients between 2 h blood glucose and levels of glycated haemoglobin were between 0.43 and 0.64. This poor correlation was not explained on the basis of assay or biological variability of either 2 h blood glucose or glycated haemoglobin. Multiple regression analysis showed that other assays of glycated haemoglobin contributed to the variance of any single glycated haemoglobin value by 0.1%-52.9% (median 12.8%) compared to the variance of 18.6%-41.4% (median 30.8%) explained by 2 h blood glucose alone, suggesting that in a non-diabetic population, the degree of glucose intolerance may explain only one third of the variance of glycated haemoglobin levels, but other factors operate to produce consistent changes in levels of glycated haemoglobin. Investigation of 42 subjects with consistently high (20 subjects) or low (22 subjects) levels of glycated haemoglobin relative to their 2 h blood glucose level showed no difference in age, gender, body mass index, haemoglobin levels or smoking, although 50% of low glycators had impaired glucose tolerance. Neither ambient blood-glucose levels, as estimated on two five-point blood-glucose profiles, nor dietary intake of carbohydrate, starch, sugars, fibre or alcohol, explained the difference between high and low glycators. The determinants of the consistent interindividual differences in levels of glycated haemoglobin in non-diabetic subjects remain to be determined.

Adult↗

Synthesis of prostaglandins in cholera toxin-treated Chinese hamster ovary cells.

The prostaglandin (PG) and adenosine 3',5'-cyclic monophosphate (cAMP) responses of Chinese hamster ovary (CHO) cells were measured after cholera toxin (CT) exposure to evaluate dose and kinetic relationships. Release of prostaglandin E2 (PGE2) and the accumulation of cAMP were dependent on the dose of CT, with an effective dose of approximately 10-100 ng/ml within 4 h; the PGE2 response was about four- to six-fold more than that of PGE1. CHO cells exposed to CT also released increased amounts of thromboxane B2 (TxB2), PGF2 gamma, and 6-keto PGF1 gamma (a non-enzymatic degradation product of prostacyclin). Kinetic analysis of CT-treated cells revealed that small peaks of cAMP accumulation and of PGE1 and PGE2 release were detected at approximately 30 min, but larger, progressive PG and cAMP responses were measured 2-4 h later. Exposure of the cells to relatively high doses of membrane-permeable derivatives of cAMP (1 mM) and forskolin (10 microM) caused PGE2 release. Concomitantly, exogenous PGE2 (100 microM) increased intracellular levels of cAMP. We have considered the interrelationship of the cyclo-oxygenase and the cyclic nucleotide pathways relative to the molecular mechanism of CT.

Alprostadil↗

Slowly progressive aphasia: three cases with language, memory, CT and PET data.

Three cases of slowly progressive speech and language disturbance were studied at various points post onset (three, five and 15 years respectively). Language, neuropsychological and brain imaging (computer tomography and positron emission tomography) evaluations were completed on all three patients. The data suggest that the syndrome of "progressive aphasia": 1) does not involve a uniform symptom complex; 2) does not necessarily develop into a full blown dementia syndrome; 3) varies greatly in rate of progression from case to case; 4) is associated with normal brain structure (on computer tomography); and 5) is associated with abnormal left temporal lobe metabolism as measured by fluorodeoxyglucose (FDG) positron emission tomography (PET). One patient had histological findings consistent with Alzheimer's disease at necropsy.

Aged↗

The impact of prospectively set hospital budgets on psychiatric admissions.

This article examines the impact of prospectively set hospital budgets on rates of admission of psychiatric patients in New York state, U.S.A. The analysis takes advantage of a natural experiment which took place in the early 1980s, whereby a geographic region adopted a prospective hospital budget reimbursement scheme that differed from the prospective per diem reimbursement scheme used in the rest of the state. The results indicate a strong decrease in psychiatric admissions attributable to the experimental payment method.

Admitting Department, Hospital↗

Trimethoprim resistance transposon Tn4003 from Staphylococcus aureus encodes genes for a dihydrofolate reductase and thymidylate synthetase flanked by three copies of IS257.

Trimethoprim resistance mediated by the Staphylococcus aureus multi-resistance plasmid pSK1 is encoded by a structure with characteristics of a composite transposon which we have designated Tn4003. Nucleotide sequence analysis of Tn4003 revealed it to be 4717 bp in length and to contain three copies of the insertion element IS257 (789-790 bp), the outside two of which are flanked by directly repeated 8-bp target sequences. IS257 has imperfect terminal inverted repeats of 27-28 bp and encodes for a putative transposase with two potential alpha-helix-turn-alpha-helix DNA recognition motifs. IS257 shares sequence similarities with members of the IS15 family of insertion sequences from Gram-negative bacteria and with ISS1 from Streptococcus lactis. The central region of the transposon contains the dfrA gene that specifies the S1 dihydrofolate reductase (DHFR) responsible for trimethoprim resistance. The S1 enzyme shows sequence homology with type I and V trimethoprim-resistant DHFRs from Gram-negative bacteria and with chromosomally encoded DHFRs from Gram-positive and Gram-negative bacteria. 5' to dfrA is a thymidylate synthetase gene, designated thyE.

Amino Acid Sequence↗

Visual cortex development in the ferret. I. Genesis and migration of visual cortical neurons.

The production of ferret visual cortical neurons was studied using 3H-thymidine autoradiography. The genesis of cortical neurons begins on or slightly before embryonic day 20 (E20) of the 41 d gestational period, continues postnatally until 2 weeks after birth (P14), and follows an inside-out radial gradient with neurons for the deeper cortical layers being generated before those for the superficial layers. Layer I neurons are generated both early (E20-E30) and late (P1-P14) in the period of cortical neurogenesis and, thus, provide at least a partial exception to the inside-out gradient of cortical neurogenesis. Tangential gradients of cortical neurogenesis extend across areas 17 and 18 in both the anterior-to-posterior and lateral-to-medial directions. Neither of these gradients bears a meaningful relationship to the cortical representation of the visual field. Most infragranular and granular layer neurons are generated prenatally, while most supragranular layer neurons are produced postnatally. Neurons destined for a given layer are produced over a period of several days, and the neurons generated on any given day contribute to the formation of 2 or more cortical layers. In general, prenatally generated neurons complete their migration in 1 week or less, while most postnatally generated neurons require approximately 2 weeks to complete their migration.

Animals↗

Microalbuminuria as predictor of vascular disease in non-diabetic subjects. Islington Diabetes Survey.

The relation between urinary albumin excretion rate (AER) and vascular disease was studied in 187 subjects aged over 40 selected from 1084 cases attending a diabetic screening project. AER exceeded 20 micrograms/min in 3 of 13 newly diagnosed diabetic subjects (23%) and 16 of 171 non-diabetic subjects (9.4%). There was a weak relation between AER and both systolic and diastolic blood pressures. Coronary heart disease was found in 54 of 164 (32.9%) subjects with AER of 20 micrograms/min or less and in 14 of 19 (74%) with AER above this. Peripheral vascular disease was present in 16 of 165 (9.7%) subjects with AER of 20 micrograms/min or less and 8 of 18 (44%) with a high AER. Logistic regression, including diabetes, impaired glucose tolerance, systolic and diastolic blood pressures, smoking, age, sex, ethnic origin, and body mass index, demonstrated the independence of this relation between AER above 20 micrograms/min and coronary heart disease (odds ratio [OR] 6.38, 95% confidence interval 1.91-21.4) and peripheral vascular disease (OR 7.72, 2.14-27.8). After a mean of 3.6 (SD 0.19) years, 167 subjects (89.3%) were traced. There had been 9 deaths, 3 (2.0%) among 149 subjects with normal AER and 6 (33%) among 18 microalbuminuric subjects (OR 24.33, 5.40-109.7).

Adult↗

Disconnection and cerebral metabolism. The case of conduction aphasia.

Ten patients with conduction aphasia were studied with computed tomography and 18-F-fluorodeoxyglucose positron emission tomography to examine glucose metabolism. Computed tomographic results identified a postrolandic structural locus for conduction aphasia. All patients demonstrated resting glucose hypometabolism throughout the parietal and temporal regions, and half of the patients also demonstrated reduced metabolic rates in the posterior, inferior, frontal (Broca's) regions. These data suggest that disconnection between posterior and anterior language areas may not be the best anatomical explanation for conduction aphasia.

Adult↗

Subcortical structures in aphasia. An analysis based on (F-18)-fluorodeoxyglucose, positron emission tomography, and computed tomography.

Subcortical structural damage that includes the anterior and posterior internal capsule, caudate, thalamus, lenticular nuclei, and insula has been shown to cause aphasias. A critical question that has not been resolved is whether the role of these structures on behavior is a direct one or whether it is indirect through the cortex. We have used pathway analysis to evaluate computed tomography, glucose metabolic, and language data from 47 aphasic patients to answer this question. For fluency (from the Western Aphasia Battery), subcortical structural damage had direct and indirect (through frontal lobe) effects on the behavior. For a comprehension task (sequential commands), subcortical damage had no direct effect and only a slight indirect effect through the temporal lobe. Thus, both direct and indirect effects of subcortical damage can be demonstrated for specific behavioral measures.

Adult↗

The relationship of hospital admission and fatality from myocardial infarction to glycohaemoglobin levels.

We have performed a study to assess the relative contributions of increased hospital admission rates with acute myocardial infarction and increased hospital case fatality to the excess mortality of subjects with elevated levels of glycohaemoglobin from myocardial infarction. Glycohaemoglobin levels were estimated by isoelectric focussing in 397 subjects without known diabetes mellitus admitted with myocardial infarction and compared with a control population reconstructed from a community sample of 1084 subjects without known diabetes mellitus screened in general practice. In the case-control comparison, glycohaemoglobin levels above the 90th centile were associated with relative risks of 3.1 (95% confidence interval 1.4-6.8) for admission with myocardial infarction and 5.3 (95% confidence interval 2.1-13.4) for death in hospital. Elevated glycohaemoglobin on admission was a predictor of both death and cardiac pump failure among those admitted with myocardial infarction, as was the presence of known diabetes. In those over 40 years of age, the top 1% of the glycohaemoglobin distribution contribute 4.3% of admissions and 9.6% of hospital deaths with myocardial infarction.

Age Factors↗

The abbreviated glucose tolerance test in screening for diabetes: the Islington Diabetes Survey.

The World Health Organization has recommended a single 2-h post-glucose load blood glucose level as a screening test for diabetes mellitus in epidemiological surveys. We have assessed its characteristics, when compared with a full supervised glucose tolerance test (OGTT), in estimating prevalence, and in diagnosing diabetes in the individual patient. A stratified sample of 223 of 1040 subjects who had participated in a diabetic survey that utilized a single capillary 2-h blood glucose estimation as a screening test were recalled for formal glucose tolerance testing. The numbers of subjects with diabetes at screening and at recall were similar (14/212, 6.6%; 13/216, 6.0%) but only 9 subjects were so classified on both occasions. Thirty-five subjects (16.5%) were suspected of having impaired glucose tolerance (IGT) at screening, and 52 (24.1%) at recall. There was substantial reclassification from screening IGT, with 3/35 worsening to diabetes, and 10/35 returning to normal. Capillary 2-h glucose levels gave an accurate assessment of the prevalence of diabetes but underestimated that of IGT. On the full OGTT, little difference in classification was found when the values of fasting and 1-h blood glucose were used in addition to those of the 2-h blood glucose used alone. The 2-h glucose had a within-subject coefficient of variation of 32.4% which produced substantial reclassification of subjects with levels close to the diagnostic levels for diabetes, and this implies that such individuals should not be classified as having diabetes on the basis of a single glucose tolerance test.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Aging and luminance-adaptation effects on spatial contrast sensitivity.

Contrast sensitivity as a function of target luminance for four spatial frequencies (0.5, 2, 4, and 8 cycles/deg) was measured in younger (n = 12; age range, 19-35 years) and older (n = 11; age range, 68-79 years) adults in order to examine the feasibility of optical and neural explanations for the impairment of contrast sensitivity in older adults. All subjects were free from identifiable ocular disease and had good acuity. Sensitivity for each spatial frequency was measured at eight luminance levels spanning 3.5 log units in the photopic-mesopic range. When gratings were flickered at 0.5 Hz, functions for older adults were displaced downward on the sensitivity axis across all luminance levels, and the slopes of these functions were steeper than those for younger adults, suggesting that optical mechanisms alone cannot account for the vision loss in older adults. Further measurements, in which spatial targets were flickered at 7.5 Hz, indicated that this faster temporal modulation affected sensitivity as a function of luminance differentially in younger and older adults. These data imply that the neural mechanisms subserving human spatial vision undergo significant changes during adulthood.

Adaptation, Physiological↗

Sodium and blood pressure: positive associations in a north London population with consideration of the methodological problems of within-population surveys.

Blood pressure (BP) and 24-hr urinary sodium (Na) and potassium (K) excretion were measured in 58 men and women aged 40 and above who were selected randomly from the age-sex register of a general practice in North London. All 58 urine collections were reported as complete, but only 28/56 (50%) were classified as 'complete' by the excretion of a biological marker, p-aminobenzoic acid (PABA). Reliability of Na excretion estimated from repeated urine collections was 0.86, indicating that variability of Na excretion within individuals in this middle-aged and elderly population was low. Systolic blood pressure (SBP) was significantly related to 24-hr Na excretion and to 24-hr Na/creatinine ratio. After adjustment for age, sex and body mass index, a SBP-Na regression coefficient of 0.091 mmHg/mmol Na (P = 0.02) was observed. On simple regression analysis, a significant association was also found between diastolic blood pressure and Na (P = 0.04). In the sub-group classified as 'complete' collectors by PABA excretion, BP-Na regression coefficients were larger than in analyses of the sample as a whole. BP was not significantly related to K or Na/K.

4-Aminobenzoic Acid↗

Four assay methods for glycated hemoglobin compared as screening tests for diabetes mellitus: the Islington Diabetes Survey.

We assessed the utility of four methods of glycated hemoglobin assay (agar gel electrophoresis with Schiff base, agar gel electrophoresis with prior removal of Schiff base, boronate affinity chromatography, and isoelectric focusing) as screening tests for diabetes mellitus, studying 223 subjects undergoing an oral glucose-tolerance test after fasting and 2 h after ingestion of 75 g of glucose. Assessment of glucose tolerance status according to the 1980 World Health Organization diagnostic criteria indicated that 13 subjects (5.8%) had diabetes, 48 (21.5%) had impaired glucose tolerance, and nine (4.0%) could not be classified (six of these because of missing values). Use of receiver-operating characteristic curves to compare the assays as screening tests showed the affinity chromatography assay to be superior. Assays for glycated hemoglobin after fasting had better precision than post-glucose-load assays as screening tests, and test characteristics of glycated hemoglobin assays on fasting subjects were similar to those of the blood-glucose estimation after fasting. We conclude that measurement of glycated hemoglobin may be a useful screening test for diabetes, and that such measurement of stable glycated hemoglobin is as accurate as measurement of fasting blood-glucose in screening for diabetes. For this use, we found methods that measure stable glycated hemoglobin superior to that measuring both stable and labile Schiff-base fractions.

Blood Glucose↗