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© 2018, The Author(s). Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Background and aims Carotid plaque size and the mean common carotid intima-media thickness measured in plaque-free areas (PF CC-IMTmean) have been identified as predictors of vascular events (VEs), but their complementarity in risk prediction and stratification is still unresolved. The aim of this study was to evaluate the independence of carotid plaque thickness and PF CC-IMTmean in cardiovascular risk prediction and risk stratification. Methods The IMPROVE-study is a European cohort (n = 3703), where the thickness of the largest plaque detected in the whole carotid tree was indexed as cIMTmax. PF CC-IMTmean was also assessed. Hazard Ratios (HR) comparing the top quartiles of cIMTmax and PF CC-IMTmean versus their respective 1–3 quartiles were calculated using Cox regression. Results After a 36.2-month follow-up, there were 215 VEs (125 coronary, 73 cerebral and 17 peripheral). Both cIMTmax and PF CC-IMTmean were mutually independent predictors of combined-VEs, after adjustment for center, age, sex, risk factors and pharmacological treatment [HR (95% CI) = 1.98 (1.47, 2.67) and 1.68 (1.23, 2.29), respectively]. Both variables were independent predictors of cerebrovascular events (ischemic stroke, transient ischemic attack), while only cIMTmax was an independent predictor of coronary events (myocardial infarction, sudden cardiac death, angina pectoris, angioplasty, coronary bypass grafting). In reclassification analyses, PF CC-IMTmean significantly adds to a model including both Framingham Risk Factors and cIMTmax (Integrated Discrimination Improvement; IDI = 0.009; p = 0.0001) and vice-versa (IDI = 0.02; p < 0.0001). Conclusions cIMTmax and PF CC-IMTmean are independent predictors of VEs, and as such, they should be used as additive rather than alternative variables in models for cardiovascular risk prediction and reclassification., published version, peerReviewed

Advanced glycation end products (AGEs) accumulate during renal failure and dialysis. Kidney transplantation is thought to reverse this accumu- lation by restoring renal function. Using a noninvasive and validated autofluo- rescence reader, we evaluated AGE levels in 285 transplant recipients (mean age, 52 years; range, 41 to 60 years), 32 dialysis patients (mean age, 56 years; range, 43 to 65 years), and 231 normal control subjects (mean age, 51 years; range, 40 to 65 years). Measurements in transplant recipients were performed for a mean of 73 months (range, 32 to 143 months) after transplantation. Dial- ysis patients were on dialysis therapy for a mean of 42 months (range, 17 to 107 months). Fluorescence was significantly increased in dialysis patients com- pared with normal control subjects (2.8 vs. 2.0 arbitrary units (a.u.), P < .0001). Although fluorescence levels were significantly decreased in transplant recipi- ents compared with dialysis patients (2.5 vs. 2.8 a.u., P < .0001), fluorescence in transplant recipients was higher than in controls (2.5 vs. 2.0 a.u., P < .0001). In transplant recipients, fluorescence correlated positively with the duration of dialysis prior to transplantation (R = 0.21, P < .0001), and negatively with cre- atinine clearance (R = 0.34, P < .0001). No correlation was found between time after transplantation and fluorescence in transplant recipients (R = 0.10, P = .10). Fluorescence in dialysis patients was positively correlated with duration of dialysis (R = 0.36, P = .042). Our results, like those of others, sug- gest that kidney transplantation does not fully correct increased AGE levels found in dialysis patients. The increased AGE levels in kidney transplant recip- ients cannot be explained by the differences in renal function alone. The avail- ability of a simple, noninvasive method (AGE-Reader) to measure AGE accumulation may be used to monitor AGE accumulation in a clinical setting as well as in a study setting.

Objective— To investigate whether several different measures of carotid intima-media thickness (IMT) progression are associated with subsequent vascular events and whether such associations are independent of baseline carotid atherosclerotic profile and Framingham risk factors. Approach and Results— A longitudinal cohort study (the Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population study) was performed in 7 centers in 5 European countries (Finland, France, Italy, the Netherlands, and Sweden). Three thousand four hundred eighty-two subjects (median age 64.1 years; 47.8% men) with ≥3 vascular risk factors were recruited and monitored for a postprogression median follow-up of 21.5 months, during which time 129 subjects experienced a first vascular event (incidence of 20.4 per 1000 person-years). The 15th month progression of mean and maximum carotid IMT of the left and right common carotids, bifurcations, internal carotid arteries, and their composite measures, as well as the fastest IMT max progression (Fastest-IMT max-progr ) detected in the whole carotid tree regardless of location, were used in statistical analyses. All carotid IMT measures showed significant progression during the first 15 months ( P max-progr was significantly associated with the risk of subsequent vascular events. The Fastest-IMT max-progr association persisted after Bonferroni correction for multiple comparisons and after adjustments for Framingham risk factors and pharmacological treatments (all P P =0.003). Conclusions— The Fastest-IMT max-progr , a novel approach to assess carotid IMT progression, identifies focal increases of carotid IMT and, in contrast to other progression variables, is associated with cardiovascular risk.

The focus of this article is to clarify the meaning of international competitiveness at the country level within in the context of Porter’s (1990a) thesis that countries, like companies, compete in international markets for their fair share of the world markets. At a country level, there are two schools of thought on country competitiveness: the economic school, which rejects Porter’s notion of country competitiveness, and the management school, which supports the notion of competitiveness at a country level. This article reviews and contrasts the theories pertaining to these two schools of thought with specifi c reference to trade theories and the ‘theory’ of the competitive advantage of nations originally advanced by Porter (1990a, 1997a, 1998b, 1998c, 2000). Although Porter’s Diamond Framework has been extensively discussed in the management literature, its actual contribution to the body of knowledge in the economic and management literature has never been clarified. The purpose of this article is to explain why Porter’s Diamond Framework is not a new theory that explains the competitiveness of countries but rather a framework that enhances our understanding of the international competitiveness of firms.

Historical and recent evidence is documented to demonstrate that the eastern limit of the major kelp-bed forming seaweed Ecklonia maxima has moved c. 73 km eastward along the south coast of South Africa since 2006, after remaining unchanged for almost 70 years. A significant population has established at Koppie Alleen, De Hoop Nature Reserve, which has been monitored from 2008 to 2011. It is hypothesised that the eastward spread is limited by aspects of the inshore water temperature regime, and recent evidence suggests that gradual cooling along this coast may have caused the change in distribution. It seems likely that if a cooling trend continues along the South African south coast, kelp beds and their associated species will move farther eastward in future decades, affecting the ecology and livelihoods along this coast.Keywords: biogeography, climate change, Laminariales, temperatureAfrican Journal of Marine Science 2012, 34(1): 147–151

OBJECTIVE- Several national and international scoring systems are used to diagnose diabetic polyneuropathy (PNP). The variety in these scores and the lack of data on validity and predictive value has led to a comparison and validation of the scores with clinical standards for PNP to determine the most powerful measurement for screening. RESEARCH DESIGN AND METHODS- Three matched groups were selected: 24 diabetic patients with neuropathic foot ulcers, 24 diabetic patients without PNP or ulcers, and 21 control subjects without diabetes. In all participants the scores from the International Consensus on the Diabetic Foot (ICDF) and the Dutch Nederlandse Diabetes Federatie-Centraal Beleids Orgaan (NDF/CBO) were tested. The Diabetic Neuropathy Symptom score, the Diabetic Neuropathy Examination score, Heart Rate Variability, the Nerve Conduction Sum score, and a San Antonio Consensus sum score were obtained as clinical standards. Reproducibility was tested in a separate study (13 patients). RESULTS- The construct validity and discriminative power of the ICDF and NDF/CBO scores were comparable, although monofilaments (NDF/CBO) scored lower. The predictive value was good for all scores, with the best results being obtained for the tuning fork (NDF/CBO). Reproducibility of the NDF/CBO scores (monofilaments and tuning fork) was high. CONCLUSIONS- The characteristics of the scores of tests recommended by ICDF and NDF/CBO are comparable. The single use of the 128-Hz tuning fork produces results similar to the extended scores of the ICDF and much better than those of monofilaments on validation and for predictive value. For screening we therefore advise the use of the tuning fork alone.

Aims Little is known about the regulation of phospholipid transfer protein (PLTP), that plays a key role in lipoprotein metabolism. PLTP secretion may be up-regulated by glucose in vitro, whereas plasma PLTP activity is decreased by exogenous hyperinsulinaemia and glucose-induced hyperinsulinaemia in vivo. In the present study, we evaluated the separate effects of hyperglycaemia and hypermsulinaemia in C-peptide-negative Type 1 diabetic patients. Methods The protocol was carried out in 16 patients (eight females). In each individual, plasma PLTP mass and activity (measured by enzyme-linked immunosorbent assay and liposome-high density lipoprotein system, respectively) as well as plasma cholesteryl ester transfer protein (CETP) activity, lipids and apolipoprotein levels were determined at the end of four different glucose clamps, each lasting 210 min: standard insulin (30 mU/kg/h) and standard glucose (glucose 5.0 mmol/l) (SI-SG), standard insulin and high glucose (glucose 12 mmol/l) (SI-HG), high insulin (150 mU/kg/h) and standard glucose (HI-SG), and high insulin and high glucose (HI-HG). Results Plasma lipids and (apo)lipoproteins, measured at the end of the SI-HG, HI-SG and HI-HG clamps, were not significantly different compared with the levels obtained at the end of the SI-SG clamp. Median plasma PLTP mass and activity at the end of the SI-SG clamp were 12.8 mg/l and 13.2 eta mol/ml/h, respectively. Median plasma PLTP mass decreased by 9.1 % at the end of the HI-HG clamp (P

OBJECTIVE Several lines of evidence suggest that the GH-IGF-1 axis affects capillary permeability and angiogenesis. We evaluated skin capillary permeability and capillary density in GH-deficient adults, before and after GH replacement therapy. PATIENTS Seven normotensive, nondiabetic GH-deficient adults (two women) were matched with 14 control subjects. MEASUREMENTS Large-window videodensitometry with sodium fluorescein was performed in all subjects. Capillary permeability was expressed as the average relative light intensity over the first 7 min after the appearance of fluorescein in the skin capillaries; l(av)(7). Skin capillary density was determined by counting the visualized capillaries and was expressed as n/mm(2). The GH-deficient patients were restudied after 12 months of GH replacement therapy (2 U/day). RESULTS Both capillary permeability and capillary density were lower in untreated GH-deficient patients than in control subjects (median, interquartile range): I-av(7) in GH-deficient patients 47.1 (45.1-52-2)% vs. 57.5 (50.5-64.8)% in controls, P

We wondered whether, in an elderly hypertensive population in a primary prevention setting, free from diabetes mellitus and clinical atherosclerosis, differences between end organ damage and microalbuminuria (MA) could be found using a lower level of urinary albumin excretion than that of classically defined MA. From a population survey of 173 previously untreated hypertensive patients (4x blood pressure systolic greater than or equal to 160 and less than or equal to220 mmHg, and/or diastolic greater than or equal to95 and less than or equal to115 mmHg), mean age 67 +/- 4 years, were screened for MA (defined as albumin excretion between 20 and 300 mg/24 h). End organ damage was determined by B-mode ultrasound scanning of carotid and femoral arteries and echocardiography. Out of 173 hypertensives, 14 showed MA (8%,). These hypertensives had a significantly higher intima media thickness (IMT; 1.01 +/- 0.21 vs 0.88 +/- 0.6 mm, p

Background: Endothelial dysfunction is useful in predicting future cardiovascular disease. At present several tests are available to test endothelial function: coronary diameter response to acetylcholine, forearm bloodflow (FBF) response to acetylcholine, and brachial artery flow-mediated dilative (FMD) response to postischemic hyperemia. This study aimed to compare the three most frequently reported endothelial function tests. Methods: Twenty-eight patients (19 males and nine females, mean age 57 years) referred for diagnostic coronary angiography were considered for endothelial function measurement in the coronary artery as well as in the forearm by FBF and FMD. Results: Acetylcholine decreased the mean coronary diameter by 7.4% (SD 6.3%) and increased the mean FBF by 230% (SD 152%). Hyperemia increased the mean brachial diameter by 6.7% (SD 4.8%). The effect of acetylcholine on forearm resistance vessels was significantly related to the effect of acetylcholine on the coronary conduit vessels (P=0.039). Nonetheless, FMD was not related to FBF nor to the coronary response. Conclusion: In patients with mild coronary endothelial dysfunction, forearm vasoreactivity is related to the coronary response, provided that the same stimulus is used.

Aims To compare the effects of two long-acting calcium antagonists of different types on cardiovascular,tress responses in hypertension. Methods One-hundred and forty-five patients with mild to moderate hypertension and a mean (+/- s.e.mean) age of 51 +/- 0.9 years received for 8 weeks the phenylalkylamine verapamil sustained release (240 mg) and the dihydropyridine amlodipine (5 mg) in a double-blind cross-over design, both after 4 weeks of placebo. Blood pressure, heart rate and plasma noradrenaline were monitored during 3 min of sustained isometric handgrip and 2 min of cold pressor. Results Blond pressure was equally reduced by both drugs. After 3 min handgrip, systolic blood pressure. heart rate and rate-pressure product were lower with verapamil compared with amlodipine. Verapamil attenuated the increases in systolic blood pressure (25 +/- 2 vs 30 +/- 2 mmHg, difference 4.6, 95% CI (1.0, 8.1), P

Several studies have demonstrated the beneficial effects of 3 hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors on vascular properties, but little is known about treatment intensification. We compared patients in whom statins were started (INITIAL, n = 30) for hypercholesterolaemia (>6.5 mmol l(-1)) with a matched patient group of long-time statin users, with similar baseline characteristics for lipids, intima-media thickness (IMT), and pulse wave velocity, in whom treatment with statins was intensified (LONG-TERM, n = 54). At baseline and after 1 year, lipid profile, IMT of the carotid and femoral arteries, aortic distensibility using pulse-wave velocity and various properties of the peripheral vascular bed using a recently developed bio-impedance method were measured. After 1 year the relative changes in lipid profile were significantly better in the INITIAL compared with the LONG-TERM-group, The relative changes in IMT of the mean internal carotid and common femoral arteries significantly differed between the INITIAL and LONG-TERM-group (-8 and +11%, -11 and +22%, respectively). After 1 year, in both groups, most other vascular wall characteristics were unaltered compared with baseline. In conclusion, the beneficial structural alterations of the vascular wall were greater after starting than after intensifying already existing lipid-lowering treatment. This suggests that other effects of HMG-CoA reductase inhibitors than lipid-lowering alone must be involved in vascular changes. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

The cold face test has been found to be a simple clinical test to elicit the diving reflex, which assesses function of the sympathetic and parasympathetic nerve systems at the same time. However, there is no consensus about how the test should be performed without confounding the results by eliciting other reflexes, such as the oculocardiac reflex. The object of this study was to compare and standardize methods for per forming the cold face test. Reproducibility of results was assessed. Groups of 6 to 11 subjects participated in each protocol. To act as a cold stimulus a bag filled with iced-water and having a wet surface was used. The effects of allowing breathing to continue, of different masses of the bag, and of avoiding ocular pressure by wearing diving goggles were investigated. Blood pressure and heart rate were measured beat to beat using an automatic blood pressure measuring device. The cold stimulus used in this study was too small to elicit the oculocardiac reflex: wearing diving goggles and different masses of the bag had no influence on the response. The prevention of breathing, however, tended to enhance the fall ill heart rate during the cold stress. Reproducibility was highest when the subjects were habituated to the intensity of the stimulus. We recommend practising the test method in advance and performing it in a setting where the subject is unable to breathe.

Background Capillary leakage of sodium-fluorescein (NaF) in the skin reflects capillary permeability and may be a marker of diabetes-associated microcirculatory abnormalities. Design We evaluated transcapillary skin NaF leakage by fluorescence videodensitometry in 10 normoalbuminuric, 10 microalbuminuric Type I diabetic men (diabetes duration > 10 years) and 10 healthy subjects. The microalbuminuric patients were restudied after 6 weeks treatment with the ACE-inhibitor enalapril, 10 mg once daily. All measurements were performed at a blood glucose level of 5 mmolL(-1) . Results Transcapillary NaF leakage was strongly increased in normoalbuminuric Type 1 diabetic patients compared to healthy subjects (P

OBJECTIVE - Walking training (WT) is an established treatment for patients with intermittent claudication (IC). Abnormalities specific to diabetes, such as a relative preponderance of distal lesions and the contribution of microcirculatory disease, might well influence the results of WT. We compared changes in walking distance during WT in diabetic patients with those in nondiabetic control subjects. RESEARCH DESIGN AND METHODS - In consecutive patients with limiting IC and proven peripheral vascular disease, 33 patients with diabetes were compared with 136 control subjects during a half-year supervised WT program. Walking parameters were determined every 2 months, while vascular parameters were obtained at the start and end of the program. RESULTS - Of the 33 diabetic patients, 25 (76%) completed the program, as did 87 of the 136 (64%) control subjects. Thereafter, the symptom-free walking distance and the maximum walking distance (MWD) were significantly increased in diabetic patients from 142 +/- 30 to 339 +/- 57 m and from 266 +/- 39 to 603 +/- 52 m, respectively, and in control subjects from 176 +/- 8 to 400 +/- 39 m and from 292 +/- 18 to 628 +/- 36 m, respectively. The relative gain in MWD was 88% greater in those with diabetes. The vascular parameters were comparable for both groups before and after WT: CONCLUSIONS - WT is an effective treatment for IC, with a greater relative gain in diabetic patients.

Autonomic neuropathy is a well-known and prognostically important feature of systemic amyloidosis. In other conditions, autonomic function is commonly assessed by cardiovascular reflex rests, described by Ewing, but the feasibility of these tests has not been investigated in patients with systemic amyloidosis. We studied autonomic function in amyloidotic patients using cardiovascular tests and assessed their feasibility. Patients with AA, AL and ATTR amyloidosis participated. In all patients, cardiovascular reflex testing (mental arithmetic stress test and head-lip tilting, besides the Ewing-tests) was performed. Of the 46 patients included, only 28 patients could perform all 4 Ewing-tests. In particular, patients with AA amyloidosis secondary to rheumatoid arthritis could not perform standing up and the isometric handgrip test, However, when the mental stress test replaced the handgrip test and head-up tilting replaced standing up, in 45 of the 46 patients, autonomic function could be assessed with cardiovascular reflex tests. Half of the patients with AA amyloidosis had signs of autonomic neuropathy-which was more than expected. We propose to replace the isometric handgrip test with the mental arithmetic stress test and standing up with head-up tilting if a patient is not able to perform these tests.

Exogenous norepinephrine (NE) increases intraglomerular pressure in animal experiments, but it is unknown whether NE induces a microproteinuric response in humans. Moreover, it has not been studied whether possible microproteinuric and renal hemodynamic changes induced by NE are altered in insulin-dependent diabetes mellitus (IDDM) complicated by microalbuminuria. Therefore, the microproteinuric and renal hemodynamic responses to exogenous NE infusions were measured in eight matched normoalbuminuric IDDM patients (group D1), microalbuminuric IDDM patients (group D2), and control subjects (group C). As anticipated, mean arterial pressure (MAP)-NE dose-response curves were significantly shifted leftward in groups D1 and D2 compared with group C (P

Reflex sympathetic dystrophy (RSD) is characterized mostly by: (burning) pain, restricted range of motion, oedema and autonomic disturbances. Amputations in case of RSD patients should only be performed in cases of a dysfunctional limb, life threatening conditions such as untreatable infections or in cases of unbearable pain. The authors describe a patient in whom amputation became inevitable because of threatening infections.

The factors that determine the individual susceptibility to vasovagal syncope [VVS] are largely unknown, including the role of the autonomic nervous system. We therefore studied common vagal and sympathetic reflexes in 12 patients with WS (mean age 37 [18-75] years, 6 men). The Valsalva maneuver and deep breathing were performed to assess vagal responsiveness and mental arithmetic stress; the cold-pressor test and isometric handgrip were performed to assess sympathetic responsiveness. Standing up was per-formed to assess the combined responsiveness. With the exception of a subnormal response to deep breathing in one patient, all vagal tests were normal. In contrast, the response to mental stress, the cold-pressor test, and isometric handgrip was subnormal in 4 patients, 6 patients, and 4 patients, respectively. The response to standing up was normal in all patients. It is concluded that many patients with WS are characterized by normal vagal responsiveness, but sympathetic hyporesponsiveness. Sympathetic hyporesponsiveness might explain the inadequate vasoconstriction, which plays an important, early role in ws.

We assessed the day-to-day reproducible of vitreous fluorophotometry in 7 type 1 diabetic patients and in 1 healthy control subject. The coefficient of variation for duplicate measurements was 33.7, 40.3 and 23.6%, for the right eyes, the left eyes and mean values of both eyes, respectively. Assessment of reproducibility in 1 healthy subject, measured 4 times, resulted in coefficients of variation of about 60%. These values are somewhat worse than those obtained by others in healthy subjects. Since technical problems do not seem to play a significant role in this regard, our reproducibility results reflect the true biological variability of the permeability of the blood-retina barrier assessed by vitreous fluorophotometry in diabetic patients. This variability is substantial. Therefore, we conclude that this method is not precise enough to be used in intervention studies with a limited number of subjects.

The transcapillary and interstitial diffusion of intravenously administered sodium fluorescein is used as a marker for capillary permeability. Fluorescein diffusion has been expressed by different parameters with reported coefficients of variation of 14-20%. Aim of the present study is to select a parameter which combines excellent reproducibility with the potential for discriminating insulin-dependent diabetic patients from healthy subjects. We performed three experiments to assess day-to-day reproducibility: 5 healthy subjects were measured twice, 1 healthy subject was measured 6 times and 1 subject with insulin-dependent diabetes mellitus was measured 5 times. We averaged the relative fluorescence light intensity [I-REL(t)] from dye arrival until a certain time point [I-AV(t)], instead of using the relative intensity at one time point. I-AV(7 min) showed markedly improved reproducibility, expressed as geometric mean of the coefficients of variation of the three separate experiments: 10%. In addition, a group of 12 insulin-dependent diabetic subjects was compared with 12 healthy control subjects. Median I-AV(7 min) was 69.5% (95% CI: 65.3-78.1%) in the diabetic subjects and 54.9% (95% CI: 52.1-60.0%) in the control subjects (p

Dopamine is administered frequently in the operating theatre and intensive care unit patients undergoing mechanical ventilation with the aim of specifically enhancing renal uncontrolled, open study, sequentially different doses of dopamine (0, 2, 4, 8 and 0 mu g kg(-1) min(-1)) during a 1-h period each. Systemic haemodynamic and renal haemodynamic variables were measured simultaneously using a pulmonary artery catheter and radiopharmaceuticals, respectively. We studied seven haemodynamically stable patients (mean age 66 yr), with a serum creatinine concentration

1. Hypokalaemic periodic paralysis is characterized by attacks of muscle weakness, Glucose, insulin and an abnormal regulation of ATP-sensitive potassium channels may be involved in these attacks, We studied the effect of hyperglycaemia and of the potassium channel opener pinacidil on insulin release and muscle strength in patients with hypokalaemic periodic paralysis. 2. Insulin release was assessed on two occasions in four patients with hypokalaemic periodic paralysis and in eight matched control subjects, with and without treatment with 25 mg pinacidil orally, during a hyperglycaemic glucose clamp at a blood glucose level of 10 mmol/l, in a placebo-controlled, double-blind study, Muscle strength was measured in the hypokalaemic periodic paralysis patients before and during hyperglycaemia using a handheld dynamometer. 3. During the clamp, the mean glucose concentration (10-180 min) in control subjects was 9.9+/-0.07 and 10.0+/-0.03 mmol/l with and without pinacidil respectively, and in patients with hypokalaemic periodic paralysis was 10.0+/-0.04 and 10.1+/-0.06 mmol/l respectively (not significantly different), In both groups, the areas under the insulin curve from 0 to 10 min (first-phase insulin release) and from 30 to 180 min (second phase) were not different on the pinacidil study day compared with on the placebo day, The areas under the insulin curve of the first and second phases also did not differ between control subjects and patients with hypokalaemic periodic paralysis (with or without pinacidil). The M/I ratio, a measure of insulin sensitivity, was not different in the two groups, On the placebo day, baseline muscle strength in patients with hypokalaemic periodic paralysis was 165+/-16 N for the hip abductors and 168+/-19 N for the knee flexors, During the period of hyperglycaemia on the placebo day, muscle strength did not decrease in either muscle group, On the pinacidil study day, an increase in muscle strength was found only in the two hypokalaemic periodic paralysis patients with the lowest mean muscle strength (150 N showed no increase in muscle strength with pinacidil. 4. Insulin secretion and sensitivity were normal in patients with hypokalaemic periodic paralysis, Hyperglycaemia during hyperglycaemic clamping did not provoke paralytic attacks and did not result in a decrease in muscle strength, The potassium channel opener pinacidil had no effect on insulin secretion in hypokalaemic periodic paralysis patients or in normal subjects, Pinacidil may enhance muscle strength in those hypokalaemic periodic paralysis patients who suffer partial paralytic attacks.

Objective-To determine whether ambulatory blood pressure eight weeks after withdrawal of antihypertensive medication is a more sensitive measure than seated blood pressure to predict blood pressure in the long term. Design-Patients with previously untreated diastolic hypertension were treated with antihypertensive drugs for one year; these were withdrawn in patients with well controlled blood pressure, who were then followed for one year. Setting-Primary care. Subjects-29 patients fulfilling the criteria for withdrawal of antihypertensive drugs. Main outcome measures-Sensitivity, specificity, and positive and negative predictive value of seated and ambulatory blood pressure eight weeks after withdrawal of antihypertensive drugs. Results-Eight weeks after withdrawal of medication, mean diastolic blood pressure returned to the pretreatment level on ambulatory measurements but not on seated measurements. One;year after withdrawal of medication, mean diastolic blood pressure had returned to the pretreatment revel both for seated and ambulatory blood pressure. For ambulatory blood pressure, the sensitivity and the positive predictive value eight weeks after withdrawal of medication were superior to those for seated blood pressure; specificity and negative predictive value were comparable for both types of measurement. Receiver operating characteristic curves showed that the results were not dependent on the cut off vales that were used. Conclusion-Ambulatory blood pressure eight weeks after withdrawal of antihypertensive drugs predicts long term blood pressure better than measurements made when the patient is seated.