Risk factor measurement quality in primary care routine data was variable but nondifferential between individuals.

OBJECTIVE: To retrospectively assess the quality of cardiovascular disease risk factor measurements in routinely collected data and to examine whether there are systematic differences in measurement quality between individuals of different socioeconomic status, and changes in measurement quality over time. STUDY DESIGN AND SETTING: Comparison of last digit preference in risk factor measurement between a "routine" data set (related to a primary care-based UK cardiovascular risk factor screening programme) and relevant prospective epidemiological surveys (Health Survey for England [HSE] and WHO MONICA). For the routine data set, the records of 37,161 women and 33,977 men aged 35-60 years with a first screening episode during the 11-year period 1989-1999 were analyzed. RESULTS: Last digits of height, weight, and total cholesterol measurements in the routine data set did not exhibit a digit preference pattern, although the degree of random measurement error was greater compared with epidemiological survey data. The last digits of systolic and diastolic blood pressure (BP) measurements exhibited a strong last digit preference pattern for "0"-comprising 63.1% and 67.3% of all observations in men and women, respectively. Except for diastolic BP in men, last digit distribution patterns were not associated with participant's socioeconomic status and showed no change over time. CONCLUSION: It may be feasible to study changes over time in cardiovascular disease risk factor levels in different socioeconomic groups using routine data sets; however, prior critical examination of measurement quality is necessary.

EEG and MEG: forward solutions for inverse methods.

A solution of the forward problem is an important component of any method for computing the spatio-temporal activity of the neural sources of magnetoencephalography (MEG) and electroencephalography (EEG) data. The forward problem involves computing the scalp potentials or external magnetic field at a finite set of sensor locations for a putative source configuration. We present a unified treatment of analytical and numerical solutions of the forward problem in a form suitable for use in inverse methods. This formulation is achieved through factorization of the lead field into the product of the moment of the elemental current dipole source with a "kernel matrix" that depends on the head geometry and source and sensor locations, and a "sensor matrix" that models sensor orientation and gradiometer effects in MEG and differential measurements in EEG. Using this formulation and a recently developed approximation formula for EEG, based on the "Berg parameters," we present novel reformulations of the basic EEG and MEG kernels that dispel the myth that EEG is inherently more complicated to calculate than MEG. We also present novel investigations of different boundary element methods (BEM's) and present evidence that improvements over currently published BEM methods can be realized using alternative error-weighting methods. Explicit expressions for the matrix kernels for MEG and EEG for spherical and realistic head geometries are included.

Amniotic fluid lamellar body count: cost-effective screening for fetal lung maturity.

OBJECTIVE: To create a highly specific cascade testing scheme for fetal lung maturity using the lamellar body count, lecithin/sphingomyelin ratio (L/S), and phosphatidylglycerol. METHODS: A nondedicated hematology analyzer (Sysmex NE 1500, Toa Medical Electronics, Los Angeles, CA) was used to determine the lamellar body counts of 209 unspun amniotic fluid specimens. Maximally specific lamellar body count cutoffs for biochemical maturity and immaturity were determined using receiver operating characteristic curves. Biochemical lung maturity was defined as either a mature L/S ratio or phosphatidylglycerol. Biochemical lung immaturity was defined as both an immature L/S ratio and an immature phosphatidylglycerol. RESULTS: A lamellar body count of less than 8000 (n = 17) was 100% specific for biochemical lung immaturity (positive predictive value = 100%, negative predictive value = 86%). A lamellar body count of greater than 32,000 was 98% specific for biochemical lung maturity (positive predictive value = 99%, negative predictive value = 63%). CONCLUSION: Testing only specimens where the lamellar body count was greater than 8000 and less than or equal to 32,000 for the L/S ratio and phosphatidylglycerol would preclude the need for 76% of all L/S and phosphatidylglycerol assays. Because the lamellar body count is quick, simple, and universally available, it could serve as an extremely cost-effective screening test for fetal lung maturity.

Pleural effusion secondary to extramedullary haemopoiesis in a patient with idiopathic myelofibrosis responding to pleurodesis and hydroxyurea.

A case of idiopathic myelofibrosis presenting with a pleural effusion secondary to extramedullary haemopoeisis is described. Approximately 2 years following the diagnosis of his myeloprolioferative disorder the patient presented with dyspnoea. Physical signs were consistent with a pleural effusion which was confirmed radiologically. Cytology of the effusion fluid demonstrated myeloid precursors, including megakaryocytes. The effusion required repeated draining and a pleurodesis was undertaken in an attempt to prevent reaccumulation of the fluid. The procedure was successful and follow up over a period of 5 months demonstrated no recurrence of the pleural effusion on that side of the chest. An effusion later occurred on the other side but was managed conservatively by drainage. Hydroxyurea was introduced at that stage, but shortly afterwards the patient died from an unrelated cause. We review the literature on this uncommon complication of myelofibrosis and discuss the options available to treat the disorder.

Error bounds for EEG and MEG dipole source localization.

General formulas are presented for computing a lower bound on localization and moment error for electroencephalographic (EEG) or magnetoencephalographic (MEG) current source dipole models with arbitrary sensor array geometry. Specific EEG and MEG formulas are presented for multiple dipoles in a head model with 4 spherical shells. Localization error bounds are presented for both EEG and MEG for several different sensor configurations. Graphical error contours are presented for 127 sensors covering the upper hemisphere, for both 37 sensors and 127 sensors covering a smaller region, and for the standard 10-20 EEG sensor arrangement. Both 1- and 2-dipole cases were examined for all possible dipole orientations and locations within a head quadrant. The results show a strong dependence on absolute dipole location and orientation. The results also show that fusion of the EEG and MEG measurements into a combined model reduces the lower bound. A Monte Carlo simulation was performed to check the tightness of the bounds for a selected case. The simple head model, the low power noise and the few strong dipoles were all selected in this study as optimistic conditions to establish possibly fundamental resolution limits for any localization effort. Results, under these favorable assumptions, show comparable resolutions between the EEG and the MEG models, but accuracy for a single dipole, in either case, appears limited to several millimeters for a single time slice. The lower bounds increase markedly with just 2 dipoles. Observations are given to support the need for full spatiotemporal modeling to improve these lower bounds. All of the simulation results presented can easily be scaled to other instances of noise power and dipole intensity.

Multiple dipole modeling and localization from spatio-temporal MEG data.

An array of biomagnetometers may be used to measure the spatio-temporal neuromagnetic field or magnetoencephalogram (MEG) produced by neural activity in the brain. A popular model for the neural activity produced in response to a given sensory stimulus is a set of current dipoles, where each dipole represents the primary current associated with the combined activation of a large number of neurons located in a small volume of the brain. An important problem in the interpretation of MEG data from evoked response experiments is the localization of these neural current dipoles. We present here a linear algebraic framework for three common spatio-temporal dipole models: i) unconstrained dipoles, ii) dipoles with a fixed location, and iii) dipoles with a fixed orientation and location. In all cases, we assume that the location, orientation, and magnitude of the dipoles are unknown. With a common model, we show how the parameter estimation problem may be decomposed into the estimation of the time invariant parameters using nonlinear least-squares minimization, followed by linear estimation of the associated time varying parameters. A subspace formulation is presented and used to derive a suboptimal least-squares subspace scanning method. The resulting algorithm is a special case of the well-known MUltiple SIgnal Classification (MUSIC) method, in which the solution (multiple dipole locations) is found by scanning potential locations using a simple one dipole model. Principal components analysis (PCA) dipole fitting has also been used to individually fit single dipoles in a multiple dipole problem. Analysis is presented here to show why PCA dipole fitting will fail in general, whereas the subspace method presented here will generally succeed. Numerically efficient means of calculating the cost functions are presented, and problems of model order selection and missing moments are discussed. Results from a simulation and a somatosensory experiment are presented.

A neuromagnetic study of selective auditory attention.

Auditory event-related magnetic fields and electrical potentials were recorded from subjects who were instructed to attend to a sequence of constant pitch tones presented to one ear and ignore a concurrent sequence of tones with a different pitch presented to the other ear. Subjects' task was to detect and count longer duration 'target' tones (P = 0.1) interspersed with 'standard' tones (P = 0.4) in the attended ear and to ignore tones (both standards and targets) in the other ear. All stimuli, both attended and ignored, elicited a prominent response approximately 100 msec after tone onset (N1m). Beginning approximately 150 msec following stimulus onset, an attention-dependent modulation of the magnetic response (Ndm) was observed for each subject. In 2 subjects whose magnetic field patterns were mapped in detail, equivalent current dipole (ECD) modeling was used to estimate the sources of N1m and Ndm activity. By transforming the coordinate systems for magnetic resonance images (MRIs) and ECD solutions, the locations and orientations of ECDs were determined relative to each subject's brain structures. ECDs for both N1m and Ndm were located in auditory cortex along the posterior regions of the sylvian fissure. Monte Carlo error analyses indicated that the ECD for Ndm is near, but significantly anterior to that for N1m.

Clonidine lowers blood pressure independently of renin suppression in patients with unilateral renal artery stenosis.

The effects of 300 micrograms of oral clonidine were studied in nine patients with unilateral renal artery stenosis proved by selective renal arteriography. Blood pressure, heart rate, plasma renin activity (PRA) levels, plasma noradrenaline levels, and sedation were measured before and for eight hours after dosage. After clonidine administration, both systolic and diastolic blood pressure fell within the first hour, was maximum in the fourth hour, and remained lower than predosage levels even in the eighth hour. There was a fall in heart rate, maximum in the fourth hour. There were minimal changes in PRA levels after giving the clonidine. Plasma noradrenaline levels fell, with the maximum fall in the sixth hour. Sedation occurred within one hour of dosage and was maximum in the second hour. We conclude that in patients with unilateral renal artery stenosis clonidine causes a substantial and prolonged fall in blood pressure not accompanied by suppression of PRA levels but by a reduction in plasma noradrenaline levels. This suggests a role for central pressor mechanisms, probably linked to angiotensin II and central sympathetic activation, in the maintenance of hypertension in patients with renal artery stenosis.

Renal function, body fluid volumes, renin, aldosterone, and noradrenaline during treatment of hypertension with pindolol.

Sixteen hypertensive patients received pindolol (10-45 mg/day); mean +/- SD, 28.75 +/- 15.22) for 3-8 weeks in a placebo-controlled, single-blind, crossover study. Supine and standing blood pressures (BP) were lowered, whereas effective renal plasma flow and glomerular filtration rates (estimated from the clearances of Hippuran and EDTA during oral water loading) did not change consistently. "Blood volume" (calculated from 125I-human serum albumin space and microhaematocrit) increased, with a corresponding reduction in serum albumin but without a change in body weight or "total body water" (T2O space). The results suggest a transfer of water from the interstitial to the intravascular compartment. This was supported by estimates of "extracellular fluid volume" (EDTA space) and "interstitial volume" (EDTA) minus human serum albumin spaces) in 3 subjects. The changes produced in "blood volume" correlated with those in BP. Plasma levels of noradrenaline, renin activity, and aldosterone were reduced, as was renal aldosterone excretion. There was no correlation between the changes produced by pindolol in BP and these hormone levels. Pindolol treatment reduced serum calcium concentration. There was a strong positive correlation between changes in BP and serum calcium and renal calcium excretion.

The actions of saralasin on the renal circulation of man and dog; evidence for a sympathetic neural component to vasoconstriction.

The mechanism of renal vasoconstriction produced by saralasin and its dependence on the sympathetic nervous system was investigated in subjects with mild essential hypertension and in anaesthetized dogs. Fluid or saline was given to maximize agonist vasoconstrictor responses. The changes in renal haemodynamics produced by intravenously infused saralasin (dose 0.01-10 microgram kg-1 min-1) were assessed by clearance methods. In the patients, it induced a dose-related renal vasoconstriction which correlated with a rise in plasma noradrenaline levels. In dogs with innervated kidneys it also caused vasoconstriction. But in dogs with denervated kidneys it caused vasodilatation. Infusion at the highest dose directly into the renal artery of denervated kidneys induced only vasodilatation. We conclude that one component of the renal vasoconstriction that occurs with intravenous saralasin infusions is mediated by the renal nerves.

Long term spironolactone and the adrenal cortex in essential hypertension.

In view of recent evidence that spironolactone may inhibit synthesis of corticosteroids by a direct effect on the adrenal cortex, adrenocortical function was studied in eight patients with essential hypertension who had been treated with spironolactone from 3 months to 14 years. Their 24 h renal excretion of adrenocorticoid metabolites and the responses of cortisol, aldosterone and 18-hydroxy-11 -deoxycorticosterone (18-OH-DOC) to an incremental infusion of tetracosactrin (1-24 ACTH) were compared with those in eight patients with recently diagnosed essential hypertension who had received no spironolactone. The spironolactone-treated group had a significantly higher excretion of aldosterone, whilst the excretion of other adrenocorticoid metabolites did not differ. The same group also required less tetracosactrin to stimulate a detectable rise of plasma cortisol and 18-OH-DOC, they had greater plasma 18-OH-DOC responses at all infusion rates and, at the lowest infusion rates, had greater aldosterone responses. These results indicate that long-term spironolactone therapy does not inhibit adrenocortical function and may have some stimulatory effects.

Radioimmunoassay of plasma 18-hydroxy-11-deoxycorticosterone and its response to ACTH.

A radioimmunoassay for the measurement of 18-OH-DOC in plasma was developed using an antiserum raised against the gamma-lactone derivative. The steroids with the greatest degree of cross reaction were 18-OH-corticosterone-gamma-lactone and aldosterone-gamma-lactone which showed cross-reactivities of 1.96% and 0.47% respectively. These and other interfering steroids were eliminated by chromatography of the extracts on columns of Sephadex LH-20. The lowest limit of detection of 18-OH-DOC in 1 ml of plasma corresponded to 33 pmol-1. The intra-assay precision was 9.7, 4.8 and 2.6% at 102.0, 316.1 and 1144.0 pmol 1(-1) respectively and the interassay precision was 15.3 and 5.4% at 71.3 and 404.7 pmol 1(-1) respectively. The amount of 18-OH-DOC measured (y) which showed a high degree of correlation (r = 0.999) with the amount added (x) to plasma in the range 240--1920 pmol 1(-1) could be predicted from the linear least squares equation y = 1.006x + 31.3. The concentration of 18-OH-DOC in ten normal subjects was 172.1 +/- 39.1 pmol 1(-1) at 09.00 h, 100.9 +/- 16.9 pmol 1(-1) at 12.00 h and 95.8 +/- 33.3 pmol 1(-1) at 16.30 h. Plasma 18-OH-DOC and cortisol levels were measured after various intravenous doses of ACTH in three patient with esential hypertension. Lower doses of ACTH caused similar percentage increases in both hormones but higher doses caused considerably greater increases in 18-OH-DOC. These results confirm the ACTH dependancy of 18-OH-DOC secretion.