Analysis of six months' referrals to a "one-stop" neurovascular clinic in a district general hospital: implications for purchasers of a stroke service.

OBJECTIVE: To determine the effectiveness of a "one-stop" neurovascular clinic (NVC) in guiding the diagnosis and investigation of patients suffering a mild stroke or transient ischaemic attack (TIA). DESIGN: Six months' survey of the activity of a new neurovascular clinic (NVC). SETTING: Borders region of Scotland. SUBJECTS: Patients referred with a suspected diagnosis of stroke or TIA. RESULTS: The clinic served 23 general practices and a population of 106,000. Over a 6 month period 128 patients were referred; 93% of patients were referred by general practitioners, 5% by consultant physicians and 2% from wards in the Borders General Hospital. Most patients were independent prior to the presenting event and had minimal disability on presentation to the clinic. Patients were seen within 48 hours of referral in the majority of cases and all within five working days. However, only 52% were seen within two weeks of the onset of their symptoms. Only 50% of patients were shown to have sustained a stroke or TIA. A variety of other diagnoses mimicked vascular events including epilepsy, migraine, cranial nerve palsies and cerebral tumour. The stroke-related group differed significantly in age (P = 0.003) and in the number of patients already on aspirin (P = 0.010) but not in any other risk factor. CT scan and carotid doppler examination were considered necessary in only 47% and 24% respectively of referred patients. Only five stroke-related patients and one non-stroke-related patient needed further input from physiotherapy, occupational therapy or speech therapy. Over 90% of patients were discharged home. Patient and general practitioner satisfaction with the service received were rated at 9 (0 = very poor; 10 = excellent). CONCLUSION: Applying evidence-based medicine to patients attending a "one-stop" neurovascular clinic with minor stroke and/or transient ischaemic attack resulted in an efficient delivery of appropriate investigations and therapy to this group of patients. The NVC prevented unnecessary requests for both CT scanning and carotid doppler examination, which are valuable resources, and may have prevented admissions to hospital. Patients were anxious about their symptoms and appreciated being seen quickly and a diagnosis made. We would recommend that these clinics be set up as part of the stroke service in all district general hospitals.

Effect of bicarbonate administration on skeletal muscle intracellular pH in the rat: implications for acute administration of bicarbonate in man.

1. The effect of bicarbonate administration on the intracellular pH of rat skeletal muscle was examined by using 31P n.m.r. 2. Bicarbonate administered intraperitoneally caused a significant intracellular acidosis in rat skeletal muscle in vivo. When the bicarbonate was administered intravenously there was no such change in the pH of the skeletal muscle. 3. Bicarbonate administration by either route resulted in an elevated mixed venous partial pressure of carbon dioxide and an elevated arterial pH, but no significant change in the arterial partial pressure of carbon dioxide. The increase in arterial bicarbonate concentration after intraperitoneal injection of bicarbonate was delayed when compared with that after intravenous injection. 4. The administration of hypertonic solutions intravenously caused a transient 40-50% fall in blood pressure, which had resolved within 1 min. 5. The data suggest that the effect of bicarbonate administration on intracellular pH in vivo is related not only to carbon dioxide loading of the cell but also to the rate of change in the extracellular bicarbonate concentration.

Na+/H+ and HCO3-/Cl- exchange in the control of intracellular pH in vivo in the spontaneously hypertensive rat.

1. We have previously shown that the cytosolic acid concentration changes in skeletal muscle during contraction in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats in vivo. We have now found that this change was unaffected by 20% inhaled CO2 or by 4,4'-di-isothiocyanostilbene-2,2'-disulphonate. This is evidence that HCO3- exchange in vivo is not important in the control of cytosolic acid concentration during skeletal muscle contraction in either spontaneously hypertensive or Wistar-Kyoto rats. 2. We have also previously shown that the difference in cytosolic acid response during contraction between spontaneously hypertensive and Wistar-Kyoto rats is due to increased Na+/H+ antiporter activity in the spontaneously hypertensive rats. Our current findings suggest that this increase in Na+/H+ antiporter activity is more likely to be due to a change in the Km of the antiporter than to a change in the Vmax. We estimate that the Km of the antiporter changes in hypertension from pH 7.16 to 7.33. 3. We did not find any differences between adult spontaneously hypertensive and Wistar-Kyoto rats with regard to resting intracellular and extracellular pH and resting intracellular and extracellular HCO3- concentrations. In addition, we did not find any evidence of a difference in skeletal muscle HCO3-/Cl- exchange between adult spontaneously hypertensive and Wistar-Kyoto rats. 4. At rest, skeletal muscles of the spontaneously hypertensive and Wistar-Kyoto rats have the same lactate production, HCO3-/Cl- exchange and arterial partial pressure of CO2. In addition, we can also calculate that at a resting intracellular pH of 7.05 in the spontaneously hypertensive rats, the antiporter is 66% saturated.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of beta 2-adrenoceptor stimulation and blockade of L-type calcium channels on in vivo Na+/H+ antiporter activity in rat skeletal muscle.

We have studied the in vivo response of the Na+/H+ antiporter in skeletal muscle to beta 2-adrenoceptor stimulation with isoprenaline and the effect of blocking L-type calcium channels with nifedipine. Na+/H+ antiporter activity in skeletal muscle in vivo increased after beta 2-adrenoceptor stimulation with isoprenaline; nifedipine attenuated that effect. This suggests that opening of L-type calcium channels is necessary for full activation of the Na+/H+ antiporter in skeletal muscle. Bleeding also increased Na/H+ antiporter activity, which we believe could be explained by an increase in sympathetic nervous system activity as a result of hypotension. This may be one of the mechanisms by which animals under stress prepare their skeletal muscle for exercise as part of the 'fright and flight' reaction.

Evidence for altered Na+/H+ antiport activity in cultured skeletal muscle cells and vascular smooth muscle cells from the spontaneously hypertensive rat.

1. Intracellular pH and Na+/H+ antiport activity were determined by a fluorimetric method in cultured skeletal muscle cells (myoblasts) and aortic vascular smooth muscle cells from spontaneously hypertensive and normotensive Wistar-Kyoto rats. 2. The intracellular pH was significantly more alkaline at three different extracellular pH values in both myoblasts and vascular smooth muscle cells from the spontaneously hypertensive rats than in those from the normotensive control rats. 3. A kinetic analysis of the Na+/H+ antiport activity in these cells showed that the raised activity in the spontaneously hypertensive rats was due to an increased maximal transport capacity in vascular smooth muscle cells and to an increase in the affinity of the antiport for internal H+ in the myoblasts. 4. When the extracellular pH was reduced in the skeletal muscle cells of both types of rat, the intracellular pH fell. However, in vascular smooth muscle cells, a reduction in the extracellular pH was not associated with a fall in the intracellular pH. This resistance of the intracellular pH to changes in the extracellular pH differentiates vascular smooth muscle cells from other cells that have been studied in this way.

Evidence for increased in vivo sodium-potassium pump activity and potassium efflux in skeletal muscle of spontaneously hypertensive rats.

We have used 87Rb nuclear magnetic resonance spectroscopy (NMR) to study in vivo rubidium kinetics in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) controls, using rubidium as a marker for potassium. We gave 15 male, 13-week-old SHR, mean +/- s.d. blood pressure 180 +/- 10 mmHg, and 15 age-matched normotensive controls, mean blood pressure 120 +/- 9 mmHg, a daily dose of RbCl (2 mmol/kg intraperitoneally). We made repeated NMR measurements of skeletal muscle rubidium concentrations until steady state was reached. We then withdrew rubidium and made further measurements of rubidium concentrations, at intervals, for up to 1 week after the last injection. We also measured plasma and erythrocyte rubidium concentrations by flame atomic absorption spectroscopy at similar intervals after the withdrawal of rubidium. Rubidium concentrations rose at a faster rate in SHR skeletal muscle, but the steady-state muscle rubidium concentration was the same (45 mmol/l) in both SHR and WKY rats. There was also a threefold increase in the rate of rubidium efflux from both muscle and erythrocytes in SHR. These results are consistent with a marked increase in Na+,K(+)-ATPase activity and an increase in the rate of rubidium efflux in vivo in SHR. The increased rate of rubidium efflux in SHR could represent increased K+ efflux via calcium-activated K+ channels and/or result as part of cell volume regulation secondary to increased Na(+)-H+ antiporter activity.

Evidence for increased in vivo Na(+)-H+ antiporter activity and an altered skeletal muscle contractile response in the spontaneously hypertensive rat.

We have assessed the in vivo activity of the Na(+)-H+ antiporter skeletal muscle in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) controls using phosphorus (31P) nuclear magnetic resonance spectroscopy to measure changes in cytosolic acid concentrations during isometric contraction. During contraction there was a small rate of rise in skeletal muscle cytosolic acid concentration to a smaller maximum concentration in SHR. This difference in acid response was removed by amiloride and was not attributable to differences in cell buffering or the rate of production of lactic acid, suggesting that the difference in acid response in SHR skeletal muscle is due to increased in vivo Na(+)-H+ antiporter activity. Amiloride reduced resting muscle glycogen concentration and increased muscle lactate concentration in the SHR. This could be related to altered in vivo calcium metabolism. The maximum tension produced by skeletal muscle during contraction in SHR was less than in WKY rats, and relaxation between twitches was significantly greater, consistent with the finding of increased vascular smooth muscle relaxation in essential hypertension. Since increased Na(+)-H+ antiporter activity occurs in association with increased relaxation of both skeletal and vascular smooth muscle, these data are not consistent with a relationship between increased Na(+)-H+ antiporter activity and increased maximal muscle tension development. However, they show that increase Na(+)-H+ antiporter activity is associated with increased muscle relaxation.

A non-invasive method of measuring concentrations of rubidium in rat skeletal muscle in vivo by 87Rb nuclear magnetic resonance spectroscopy: implications for the measurement of cation transport activity in vivo.

1. We have used n.m.r. spectroscopy to measure rubidium concentrations in the skeletal muscle of live intact rats. Using a 1.9 T superconducting magnet and an ear-phone coil tuned to both protons (1H) and rubidium (87Rb), it was possible to make measurements of both tissue rubidium content and water content, and from these measurements to obtain the rubidium concentration. 2. The n.m.r. estimate of rubidium concentration in muscle in vivo was found to be a constant 31% (SEM 4%) of that estimated by flame atomic absorption spectroscopy in an extract of excised muscle. This is close to the predicted theoretical n.m.r. visibility of 33%. The visibility was constant for muscle rubidium concentrations ranging between 10 and 34 mmol/l. 3. Rubidium concentration measurement by this method is unaffected by variations in sample geometry, sample volume, tissue conductivity, coil tuning and amplifier gain. 4. By using this method to measure changes in tissue rubidium concentration with time in the same animal, it should now be possible to assess the activity of ion transport systems, such as sodium- and potassium-activated adenosine triphosphatase in vivo, by measuring the rates of change of tissue rubidium concentrations during the administration of rubidium salts. 5. This method could also be used to measure the absolute concentration of any n.m.r.-visible nucleus and could be applied to man.

Membranous nephropathy caused by mercury-containing skin lightening cream.

A 46 year old woman developed membranous nephropathy following the use of a mercury-containing skin lightening cream. This association has not been reported in the literature for over a decade and apparently never from this country. It is important that clinicians are aware of this usually eminently treatable cause of the nephrotic syndrome as it is likely to be missed unless specifically enquired for.