Mitigation of indirect environmental effects of GM crops.

Currently, the UK has no procedure for the approval of novel agricultural practices that is based on environmental risk management principles. Here, we make a first application of the 'bow-tie' risk management approach in agriculture, for assessment of land use changes, in a case study of the introduction of genetically modified herbicide tolerant (GMHT) sugar beet. There are agronomic and economic benefits, but indirect environmental harm from increased weed control is a hazard. The Farm Scale Evaluation (FSE) trials demonstrated reduced broad-leaved weed biomass and seed production at the field scale. The simplest mitigation measure is to leave a proportion of rows unsprayed in each GMHT crop field. Our calculations, based on FSE data, show that a maximum of 2% of field area left unsprayed is required to mitigate weed seed production and 4% to mitigate weed biomass production. Tilled margin effects could simply be mitigated by increasing the margin width from 0.5 to 1.5 m. Such changes are cheap and simple to implement in farming practices. This case study demonstrates the usefulness of the bow-tie risk management approach and the transparency with which hazards can be addressed. If adopted generally, it would help to enable agriculture to adopt new practices with due environmental precaution.

Ban on triazine herbicides likely to reduce but not negate relative benefits of GMHT maize cropping.

The UK Farm-Scale Evaluations (FSE) compared the effects on biodiversity of management of genetically modified herbicide-tolerant (GMHT) spring-sown crops with conventional crop management. The FSE reported larger weed abundance under GMHT management for fodder maize, one of three crops studied. Increased seed production may be important for the long-term persistence of these arable weeds and may benefit invertebrates, small mammals and seed-eating birds. In three-quarters of FSE maize fields, growers used atrazine on the conventionally managed half, reflecting contemporary commercial practice. Withdrawal of the triazine herbicides atrazine, simazine and cyanazine from approved lists of EU chemicals could therefore reduce or even reverse the reported benefits of GMHT maize. Here we analyse effects of applications of triazine herbicides in conventional maize regimes on key indicators, using FSE data. Weed abundances were decreased greatly relative to all other regimes whenever atrazine was applied before weeds emerged. Here, we forecast weed abundances in post-triazine herbicide regimes. We predict weed abundances under future conventional herbicide management to be considerably larger than that for atrazine used before weeds emerged, but still smaller than for the four FSE sites analysed that used only non-triazine herbicides. Our overall conclusion is that the comparative benefits for arable biodiversity of GMHT maize cropping would be reduced, but not eliminated, by the withdrawal of triazines from conventional maize cropping.

Computed tomography manifestations of tricuspid regurgitation.

Six patients undergoing dynamic contrast enhanced abdominal computed tomography (CT) for upper abdominal symptoms and signs are described. Each patient demonstrated early, intense opacification of the inferior vena cava (IVC) and hepatic veins, exceeding that in the aorta on scans through the upper abdomen. Opacification of the IVC returned to normal on more caudal slices. All six patients were found to have echocardiographically proven tricuspid regurgitation (TR). It is suggested that this sign occurs in patients with TR due to direct reflux of contrast from the right atrium into the IVC during protracted bolus injection. Additional CT findings included patchy parenchymal liver enhancement in four patients and ascites in five. Recognition of this simple sign may direct the clinician to a cardiac aetiology for upper abdominal symptoms and signs.

[Dopanergic agonists and schizophrenia]. / Agonistes dopaminergiques et schizophrénie.

The neutrotransmitter dopamine mediates its central nervous system actions via 2 types of receptors: D1 and D2, each of which exist in a low or a high affinity state. In schizophrenic patients, it appears that part of the symptomatology may be secondary to dopaminergic hyperactivity (the so called positive symptoms), whereas negative symptoms would be secondary to structural damage. Antipsychotic drugs that are used in clinics are antidopaminergic. It is interesting to note that those drugs are ineffective in part of the schizophrenic population, the chronic one. This inefficiency might be due to primary resistance or to adaptation of the central nervous system to the drugs. Some authors tried dopamine agonists to treat schizophrenic patients. Apomorphine, N-n-propylnorapomorphine, l-DOPA and bromocriptine were tried. The purpose of these substances was to desensitize dopaminergic system, or to inhibit it via presynaptic autoreceptor stimulation, depending of the study. Some authors hypothesized a drop in frontal cortical dopaminergic system to explain part of the schizophrenic symptomatology. Dopamine agonists might act at this level to enhance frontal dopaminergic activity. After those experimentations with dopamine agonist drugs, it appears that 2 of them might have efficiency and clinical use: l-DOPA and bromocriptine.

Removal of fractured pacemaker electrode tip using Dotter basket.

During attempted removal of an infected permanent pacemaker system, the electrode fractured, leaving the tined tip embedded in the wall of the left subclavian vein. The electrode tip was successfully removed using a Dotter basket retrieval kit.

Reoperation for angina after previous aortocoronary bypass surgery.

A retrospective study was carried out of the outcome of 102 patients who underwent a second operation for myocardial revascularisation, necessitated by persistence or recurrence of intractable angina after their first coronary bypass procedures. Operative mortality was 2%. During follow up of the survivors (mean interval 36.4 months) five died, two after further operation, and five underwent further surgery. Sixty eight patients reported an improvement in their symptoms, 57 of whom claimed to have little or no angina. Less favourable results were recorded for those patients reviewed with longer follow up. No useful indicators of prognosis were identified. The problem of angina in patients who have already received bypass grafts is likely to increase as more revascularisation surgery is performed. Reoperation offers a reasonable prospect of helping some of these patients, but not all will be suitable. Their long term prognosis remains uncertain.

Comparison of once daily endralazine with placebo in the treatment of hypertension uncontrolled by a beta-blocker and diuretic.

We report the first placebo controlled parallel group study of once daily endralazine (5-20 mg) in hypertension uncontrolled by a beta-blocker plus a diuretic. Following a 4-week run-in period 22 patients with a sitting mean arterial pressure (MAP) greater than 110 mm Hg were entered into the study and received either endralazine 5 mg or placebo. Blood pressure was measured 2 h and 24 h after dosing and the drug dose doubled at 2 and 4 weeks if the 24-h MAP remained greater than 110 mg Hg. The final blood pressure assessment was made after 6 weeks treatment in the 19 patients who completed the study. Three patients withdrew from the study because of side effects. The hypotensive effect (sitting) was in excess of placebo at 2 h by 15.8 mm Hg systolic (NS), 15.4 mm Hg diastolic (p less than 0.01), 15.5 mm Hg MAP (p less than 0.02) and at 24 hours by 7.7 mm Hg systolic (NS), 8.9 mm Hg diastolic (p less than 0.02) and 11.1 mm Hg MAP (p less than 0.02). This study suggests that endralazine should be prescribed twice daily.

Relationships between beat-to-beat interval and the strength of contraction in the healthy and diseased human heart.

Twenty-six adult patients, classified by clinical and catheter criteria into groups of those with normal and abnormal left ventricular function, were studied during cardiac catheterization. Right heart pacing was established, and left ventricular dP/dt was measured with end-catheter manometers. By varying the interval preceding a test beat after periods of steady pacing it was confirmed that recovery of left ventricular mechanical function (maximum dP/dt) occurs approximately 800 msec (optimum interval) after a beat. The augmentation of maximum dP/dt of the first 2 beats after an extrasystole, each spaced at the optimum interval, was also studied; the amount of potentiation was varied by alterations in extrasystolic interval. Potentiation decayed from the first to the second postextrasystolic beat with a ratio that was fixed in each individual patient. The ratio (recirculation fraction) was higher in patients with normal than in those with abnormal left ventricular function (mean +/- SD 0.52 +/- 0.10 vs 0.37 +/- 0.11, p less than .005). There was an inverse relationship between this ratio and the degree of potentiation of the first postextrasystolic beat (r = .80, p less than .001). We postulate a disturbance of excitation-contraction coupling mechanisms to explain these effects.

Correlation of angiographic and surgical findings in distal coronary branches.

In 60 consecutive patients undergoing vein graft surgery the angiographic appearances of the coronary vessels were compared with those of the vessels at operation. On the basis of lumen diameter at the potential sites for grafting it was possible to predict with reasonable accuracy from examination of the angiogram which vessels were large enough to be grafted. Angiographic predictive accuracy was 82% and was similar both for vessels which filled normally and for those which filled by collaterals. The predictive value of the angiographic assessment was similar for branches thought to be too small (predictive value 74%) and for those considered sufficiently large (predictive value 85%) to receive a vein graft. Disease of the vessel walls was found at surgery (66% of coronary branches examined) more frequently than was predicted from the angiographic appearances (33%). Previous necropsy studies have found a high prevalence of coronary atheroma in the population, yet normal angiographic appearances in the coronary arteries are not uncommon in patients undergoing investigation for suspected coronary disease. The present study showed that atheroma may be present in coronary vessels without encroaching into the vessel lumen, so that it is not evident on the angiogram. Coronary atheroma is thus present more often and is more widely distributed in the coronary tree than is indicated by coronary angiography.

Changes in water and electrolyte balance, plasma volume and composition during pregnancy in the rat.

1. Daily changes in water and electrolyte balance during pregnancy were investigated in rats housed in metabolism cages. 2. Fluid intake was significantly elevated above control values from day 13 of pregnancy, with urine output failing to be raised to the same extent. This would result in an extensive fluid retention if extrarenal fluid losses were not substantially altered. 3. Electrolyte intake increased from as early as the third day after mating with an accompanying increase in renal ionic excretion. A net retention of Na, Cl and K did not occur until the final week of pregnancy when the urinary output of these ions was reduced. 4. In a parallel study, changes in plasma volume and composition throughout pregnancy were investigated. 5. A significant increase in plasma volume occurred from day 6 of pregnancy at a time well before fluid intake or urine output were altered. This indicates either an altered extrarenal output or a shift of fluid between body fluid compartments. 6. Maternal plasma sodium and total osmolality were reduced during the last week of pregnancy despite the salt retention, suggesting an increased fetal usage. 7. Such findings are related to the known renal and endocrine changes of rat pregnancy.

The relationship between the strength of the human heart beat and the interval between beats.

In 15 patients undergoing cardiac catheterization and pacing tests, the left ventricular (LV) pressure and its maximum rate of rise (LV dP/dt max) were measured with catheter-tip manometers. Atrial or ventricular pacing at a single steady frequency (the priming frequency) was followed by a test pulse at a varying interval (test pulse interval). In 14 subjects in whom it was examined, the contractile response after the test pulse increased with test pulse interval to reach a maximum plateau value--the optimum contractile response (OCR). In five cases, further prolongation of the test pulse interval decreased the contractile response. The optimum test pulse interval occurred at 800-900 msec. An increase in the priming frequency before the introduction of the test pulse caused a progressive increase in OCR, in contrast to the minor effects on LV dP/dt max of the control beats. Similar results were recorded in four other patients in whom contractile response was assessed from the rate of rise of right ventricular pressure. These results indicate that with tachycardia, the interval between beats is insufficient to allow maximum contractile performance (presumed to be activated by calcium ions) to develop. The true effect of increasing heart rate is only revealed by the relationship between OCR and the preceding frequency of contraction.

The action-potential duration and contractile response of the intact heart related to the preceding interval and the preceding beat in the dog and cat.

1. Simultaneous measurements were made in anaesthetized dogs of monophasic action potentials from the right ventricle and of the maximum rate of rise of left ventricular pressure (dP(lv)/dt(max)). Atrio-ventricular dissociation was induced and the heart paced via right ventricular electrodes.2. A control period of steady pacing was followed by a test stimulus after a variable interval called the ;test-pulse interval'. The duration of the action potential of the test beat (measured at 70% repolarization) increased with test-pulse interval and reached an approximately steady value at intervals of 1.0-1.5 sec. This constitutes the ;electrical restitution curve'.3. An increase in the frequency of stimulation prior to the introduction of the test pulses caused a downward displacement of the electrical restitution curve.4. Stimulation at 2 Hz and paired pulse stimulation at 1 Hz (same number of stimuli per min) were introduced prior to the test pulses and produced very similar electrical restitution curves.5. For a constant frequency of stimulation in the control period, adrenaline produced downward displacement of the restitution curve.6. It is concluded that there is no obvious relationship between the restitution of the action potential duration and of the contractile response. We suggest therefore that electrical and mechanical restitution occur through separate processes, the former through time-dependent recovery in membrane conductances and the latter through time-dependent increase in availability of intracellular calcium for release.7. Contractions were introduced with a test-pulse interval shorter than the optimum, and were followed by a second test pulse fixed at the optimum interval of 0.8-1.0 sec. The second test beats were potentiated (post-extrasystolic potentiation). In isolated ejecting cat hearts, there was an optimum interval for the first test pulse to produce the greatest potentiation of the second test beat. This interval was 0.2-0.3 sec, and was shortened by an increase in frequency of stimulation prior to the first test beat.8. The interval preceding the first test pulse was then varied within a range (0.8-2.0 sec) which did not produce potentiation. These first test pulses were sometimes preceded by one extrasystole. The timing of this extrasystole was altered to vary the post-extrastolic potentiation of the first test pulse.9. Multiple regression analysis, carried out between dP(lv)/dt(max) of the second test pulse (DP(2), the dependent variable) and the action potential duration (AP(1)) and dP(lv)/dt(max) (DP(1)) of the first test pulse (independent variables) yielded correlation coefficients between 0.88 and 0.99. Each determination of the coefficient included data from beats with and without post-extrasystolic potentiation.10. It is postulated that the coefficient relating DP(2) to DP(1) in the multiple regression analysis (mean value 0.75) is an index of the proportion of calcium stored during relaxation which is released again on the next beat.11. When the decay of post-extrasystolic potentiation was examined in consecutive beats at the optimum interval, the action potential durations of these beats were found to be nearly constant. A plot of dP(lv)/dt(max) of each beat against dP(lv)/dt(max) of the previous beat yielded a curvilinear relationship which was less steep than that relating DP(2) to DP(1) in the two test pulse analysis; this was attributed to inconstancy of calcium ion entry during the action potential.

The contractile state of cat and dog heart in relation to the interval between beats.

We induced atrioventricular dissociation and initiated ventricular pacing in intact dogs and isolated cat hearts. Left ventricular pressure, its time derivative (dP/t), and action potentials were recorded. When a test pulse was introduced at varying intervals after a period of steady pacing, an optimum contractile response was obtained at an average interval of 720 msec. A similar optimum interval was obtained after pacing at various frequencies and after paired pulse stimulation but was shortened to 560 msec after infusion of epinephrine. The magnitude of the optimum contractile response increased with an increase in the frequency of prior pacing which was accompanied by an increase in the time the cell membrane was depolarized. The optimum contractile response following paired pulse stimulation was greater than that following regular pacing, with the same number of stimuli per minute and the same time of membrane depolarization. The results are explicable in terms of intracellular calcium ion recirculation with separate compartments for release to and uptake from the contractile proteins. A negative feedback control of Ca2+ inflow to the cell by intracellular Ca2+ content is postulated to explain the effect of paired pulse stimulation and shortening of action potential duration following an increase in regular pacing frequency.

Intravenous infusion of salbutamol in severe acute asthma.

Out of 62 asthmatic patients admitted to hospital with an acute exacerbation of their disease, those whose symptoms had not sufficiently improved 15 minutes after an initial intensive regimen were randomly allocated to receive an intravenous infusion of either salbutamol 10 microgram/min (20 patients) or aminophylline 1 mg/min (19 patients). During the infusions, which lasted 36 hours, peak expiratory flow rates and spirometric values improved in both groups, but differences between the groups did not achieve statistical significance. Although salbutamol may be infused safely for a prolonged period to patients with acute asthma, it has no particular advantage over aminophylline. Furthermore, in patients who respond poorly to initial intensive treatment the subsequent infusion of a bronchodilator may not increase the rate of recovery from the rate that would occur naturally.

The metabolic effects of inhaled salbutamol.

1 The metabolic effects of salbutamol (5 mg) given by intermittent positive pressure breathing have been studied in eight patients with airflow obstruction. 2 No changes in plasma nonesterified fatty acids, triglyceride, glucose, insulin or cortisol were seen 1 and 4 h after administration. 3 It is concluded that inhaled salbutamol does not cause the unwanted metabolic effects reported with oral or parenteral administration, and that this is a further indication for this route of administration.

Metabolic response to intravenous salbutamol therapy in acute asthma.

In patients suffering from an acute attack of asthma the effects of salbutamol infusion (10 microng/min) on their plasma concentrations of non-esterified fatty acids (NEFA), triglyceride, insulin, and glucose were compared with those in a group of asthmatics not requiring infusion. Salbutamol was found significantly to increase the plasma concentrations of glucose and insulin while having little effect on NEFA or triglyceride. However, NEFA concentrations were found to be significantly increased in patients with an acute attack of asthma at the time of their admission to hospital. This increase is attributed to the stress of the asthmatic attack itself.