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The relationship between salt intake and blood pressure was explored in three different areas of Northern Kashmir, where people consume large quantities of salt in tea. Six villages were selected from each area and all the available family members of every second or third house were studied. Food and salt were weighed and the intake of each family member was obtained from the amount consumed out of the total cooked. Complete data were available from 361 subjects (191 males, 170 females). There was no significant difference between the three areas as regards age, height, weight, salt intake and blood pressure. Their age ranged from 15 to 88 yrs (mean 44) and the daily salt intake ranged from 70 to 420 mmol (mean 169 mmol). No correlation was found between age and salt intake or weight but there was a significant correlation between age and systolic blood pressure (r = 0.296; P less than 0.01). Both the systolic and diastolic blood pressure correlated significantly with the salt intake with correlation coefficients of 0.385 and 0.318 respectively (P less than 0.001). Multiple regression analyses showed that the significant relationship between salt and blood pressure was unaltered by adjustment for age. Of the 361 subjects, 46 (12.7%) had a blood pressure of 160/95 mmHg or more. This study suggests a similar relationship between habitual salt intake and blood pressure in each of three different areas of Northern Kashmir.

We have investigated the relationship between cigarette smoking, packed cell volume, haemoglobin concentration, and arterial oxygen saturation (SaO2) in 114 non-smokers, 66 light smokers (1-20 cigarettes a day), and 50 heavy smokers (over 20 cigarettes a day) aged 20-75 years. Packed cell volume was greater in female heavy smokers (p less than 0.001) over 40 years of age and in all female smokers over 60 years (p less than 0.001) than in non-smoking contemporaries. Haemoglobin concentrations were higher in 40-59 year old female heavy smokers (p less than 0.05) and in male and female light (p less than 0.05) and heavy smokers (p less than 0.001) over 60 years of age than in non-smoking contemporaries. SaO2 was lower in 20-39 year old male heavy smokers (p less than 0.02) and female (p less than 0.05) light smokers and also in 40-59 year old male light and heavy smokers (p less than 0.001) and female light smokers (p less than 0.02) than in non-smoking contemporaries. It was also lower in female light (p less than 0.05) and heavy (p less than 0.02) smokers over 60 years, whereas it was higher in male light smokers over 60 (p less than 0.001). Changes in SaO2 were seen at a younger age than changes in haemoglobin concentration and packed cell volume.

1. Using a previously established method of isolating an active-sodium-transport inhibitor (ASTI) from hypothalamic cell culture medium, the inhibitor was isolated and partially purified from sequential passages through Sephadex G-25 and h.p.l.c., and its effects on de-endothelialized rabbit aortic strips were investigated. 2. ASTI caused a cumulative concentration-dependent increase in tension which reversed slowly after wash, and the wash showed an identical effect on fresh strips. 3. Ouabain, used as a control, also caused a concentration-dependent increase in tension which reached a plateau at a concentration of 10 mmol/l. Both ouabain and ASTI caused a significant potentiation of the vasoconstrictor effect of noradrenaline at concentrations of 1 nmol/l-0.1 mmol/l. 4. Both ASTI and ouabain caused a significantly greater (P less than 0.01) calcium retention than control medium in aortic strips. 5. Incubation of ASTI with prolidase, chymotrypsin and carboxypeptidase A destroyed the vasoconstrictor effects as well as its inhibitory effects on sodium, potassium-dependent adenosine triphosphatase and sodium efflux from erythrocytes, but leucine aminopeptidase was ineffective. 6. These studies suggest that hypothalamic cells in culture release a peptidic inhibitor of active sodium transport which increases vascular reactivity, potentiates vasoconstrictor effects of noradrenaline and causes calcium retention.

1. Sodium transport studies were performed in erythrocytes from normal subjects and from patients with acute myeloid leukaemia. Sodium influx and efflux rates were increased in erythrocytes from leukaemic patients. 2. The ouabain-sensitive component of sodium efflux was increased in leukaemic erythrocytes. 3. The high sodium efflux from leukaemic erythrocytes was decreased when the incubation media contained leukaemic plasma, suggesting the presence of an ouabain-like factor in the plasma. Paired experiments failed to show the presence of a similar factor in normal plasma. 4. Leukaemic erythrocytes showed a significantly greater ouabain uptake than the normal cells. 5. The results are discussed in relation to the wide-spread electrolyte disturbances in acute myeloid leukaemia.

Serum immunoglobulin levels were estimated in 19 patients with aplastic anaemia. Although the mean levels for IgG, IgA and IgM for the group as a whole were within the normal range, 8 individual cases showed low levels of one or more immunoglobulin class, suggesting a disturbance in immunoglobulin production. One of these patients had a thymoma, and another positive tests for anti-nuclear factor, but there was no evidence of auto-immune disease in the others. It is suggested that 'aplastic anaemia' may sometimes be a disease due to injury of a stem cell subserving both haemopoietic and immunological function.

To explore beneficial and harmful effects of various combinations of antianginal drugs, we compared antianginal and cardiorespiratory effects of nifedipine and isosorbide dinitrate in low and high doses in combination with nadolol, a long acting beta-adrenoceptor blocker in a double-blind study in 19 patients with stable angina pectoris. Nadolol alone and in combination with the other two drugs reduced anginal attack rate and glyceryl trinitrate consumption; the high dose isosorbide dinitrate showed a further significant (P less than 0.05) reduction in both but the high dose nifedipine did not show such a trend. sigma ST depression (all leads) was significantly (P less than 0.05) more reduced by the high dose nifedipine than by the same dose of isosorbide dinitrate in combination with nadolol. Nadolol reduced forced expiratory volume in one sec (FEV1) slightly and this effect was reversed both by isosorbide and nifedipine. Isosorbide dinitrate in combination with nadolol reduced the basal and post-exercise arterial oxygen saturation (SaO2) whereas nifedipine did not reduce the mean SaO2 below the pre-trial level. A significantly greater sigma ST depression was associated with a lower post-exercise SaO2 (less than or equal to 92%) during all treatment periods but the fall of SaO2 occurred more often during isosorbide than during nifedipine treatment periods. These studies show that both isosorbide dinitrate and nifedipine enhance antianginal efficacy of nadolol. Isosorbide dinitrate, unlike nifedipine, reduces SaO2 which is associated with a greater sigma ST depression.

To evaluate the effects of chronic smoking on exercise performance we studied 5 smokers and 7 nonsmokers of comparable age and physical characteristics. The resting heart rate in smokers (75 +/- 3 beats/min; mean +/- SD) was significantly (P less than 0.01) higher than in nonsmokers (64 +/- 5). During exercise on a bicycle ergometer the heart rate remained significantly (P less than 0.01) higher in smokers than in nonsmokers. After exercise, the heart rate in nonsmokers settled to 78 +/- 9 beats/min at 10 minutes compared with 105 +/- 11 (P less than 0.01) in smokers. Oxygen consumption was similar in both groups throughout. Beta-adrenergic blockade reduced the exercise tachycardia in both groups but the heart rate for the same workload remained significantly (P less than 0.01) higher in smokers. Beta-blockade significantly reduced (P less than 0.05) oxygen consumption in nonsmokers but not in smokers who also incurred a significantly (P less than 0.05) greater oxygen debt and had higher serum lactate levels. These differences were attributed mainly to carboxyhaemoglobinaemia and partly to the effect of prolonged smoking on the heart and on intermediary metabolism.

Plasma from volume-expanded and salt-loaded hypertensive animals and from patients with essential hypertension has been reported to inhibit Na+, K+-adenosine triphosphatase (ATPase). Inhibition of the sodium pump in vascular smooth muscle caused by such a circulating factor could increase vascular tone and sensitivity to vasoactive agents, and thereby result in arterial hypertension. Numerous efforts in the past failed to isolate the putative factor from urine and plasma. Recent studies have suggested that the hypothalamus is an important source of an endogenous Na+, K+-ATPase inhibitor, but its isolation from the tissue extracts has been rendered difficult by the presence of other cellular constituents that cause artifactual interference with the assays and purification procedures. Using an alternative approach of isolating the inhibitor from culture medium, we found that dispersed fetal rat hypothalamic neurons in a capillary culture system release a heat-stable, peptidic, low-molecular-weight, active sodium transport inhibitor that causes a reversible increase in vascular tone, sensitizes vascular smooth muscle to the vasoactive effect of norepinephrine, and possesses several characteristics of the putative endogenous digitalislike factor. This inhibitor may be a chemical mediator linking kidney, brain, and cardiovascular system in the genesis of experimental volume-expanded and salt-loaded hypertension and human essential hypertension.

An inhibitor of active sodium transport (Na+ + K+-ATPase inhibitor), partially purified from the culture medium of fetal rat hypothalamic cells, has been shown to possess vasoactive properties. In order to explore whether fetal hypothalamic neurons from spontaneously hypertensive rats produce higher concentrations of the inhibitor than produced by those from normotensive rats, we cultured hypothalamic cells from both sources. An average of 10(6) cells per hypothalamus was obtained, and heat-treated (80 degrees C for 10 minutes) culture medium (120 ml) after lyophilization yielded 0.8 g of material. After Sephadex G-15 chromatography, 0.5 g of lyophilized medium from fetal hypothalamic neurons of spontaneously hypertensive rats yielded 254 +/- 47 arbitrarily defined units of Na+ + K+-ATPase inhibitory activity compared with 238 +/- 59 units from identical material of normotensive source. These studies show that the production of the hypothalamic Na+ + K+-ATPase inhibitor is not increased at the fetal stage in the spontaneously hypertensive rats.

Na+ transport was characterized in normal human fibroblasts and neoplastic H.Ep.2 cells in order to investigate the role of the endogenous peptidic factor 'inhibitin' that is secreted by a variety of neoplastic cells (including H.Ep.2) and inhibits Na+/Na+ exchange in human erythrocytes. Although active (Na+,K+-ATPase mediated) Na+ fluxes were similar in the two cell types, H.Ep.2 cells maintained higher intracellular Na+ concentration (26 mM) compared to fibroblasts (12 mM). An analysis of passive Na+ fluxes showed a difference in the handling of Na+ via ouabain and bumetanide-insensitive transport between the two cell types: H.Ep.2 cells achieved net Na+ influx via an amiloride-sensitive pathway that was only demonstrated in fibroblasts when 10% fetal calf serum (FCS) was present. Kinetic studies were undertaken to investigate the interaction between Na+ flux via Na+/H+ and Na+/Na+ exchanges. For this purpose, an outwardly directed Na+ gradient was created by loading the cells with Na+ (Nai greater than 100 mM) to activate the reverse functioning of Na+/H+ exchange (i.e., Na+out H+in). The rates of ouabain- and bumetanide-insensitive Na+ efflux were measured over a range of extracellular Na+ concentrations (Na+o 14-140 mM). In the presence of 10% FCS, the two cell types showed different responses: in fibroblasts the Na+ efflux rate showed an inverse correlation with extracellular Na+ concentration, while H.Ep.2 cells significantly increased their rate of Na+ efflux as extracellular Na+ concentration increased. So although the thermodynamic force would direct net Na+ efflux when Na+i greater than Na+o, H.Ep.2 cells were under kinetic control to perform Na+/Na+ exchange. When exogenous inhibitin was tested on fibroblasts, the steady-state intracellular Na+ concentration increased from 14 to 19 mM (p less than 0.01). In Na+-loaded fibroblasts, serum-stimulated Na+ efflux was partially inhibitin sensitive and the maximal inhibitory effect was seen when extracellular Na+ concentration was 14 mM and presumably the Na+/H+ exchanger operating in the reverse mode. This study demonstrated that, in contrast to fibroblasts, H.Ep.2 cells have a modified Na+/H+ exchange system whereby it acts in the Na+in H+out mode without exogenous growth factor activation and resists functioning in the reversed mode. It is proposed that inhibitin is the endogenous modifier of this transport system in H.Ep.2 cells with the result that H.Ep.2 cells maintain a higher concentration of intracellular Na+ compared to fibroblasts.

An inhibitor of sodium-potassium-ATPase has been partially purified from the culture medium obtained from hypothalamic cells maintained in a capillary membrane perfusion system, and some of the properties of this inhibitory factor have been investigated. Gel filtration (Sephadex G-25 Superfine) of heat-treated medium (80 degrees C for 10 min) resulted in elution of inhibitory activity in the post-salt fraction. These fractions inhibited active (i.e. sodium-potassium-ATPase-mediated) sodium transport in intact human erythrocytes, displaced [3H]ouabain from its binding site, and directly inhibited canine kidney sodium-potassium-ATPase as measured by NADH oxidation. High-performance liquid chromatography (on Hypersil ODS) of these fractions after desalting yielded one region which showed inhibitory activity on all three assays. Inhibition of sodium-potassium-ATPase was dose-related and filtered through an Amicon UM10 membrane. Incubation of this material with dispase, carboxypeptidase A, chymotrypsin, and prolidase destroyed inhibitory activity, whereas trypsin and leucine aminopeptidase were ineffective. These studies show that hypothalamic neurones release a low molecular weight heat-stable peptide which inhibits active sodium transport, ouabain binding, and sodium-potassium-ATPase.

To study the direct effects of nocturnal hypoxemia on the heart, we recorded electrocardiographic tracings and arterial oxygen saturation (SaO2) during the night in patients with chronic obstructive airways disease. In seven "blue-bloater" patients the mean basal SaO2 was less than 80 per cent, and it fell by more than 10 per cent during 29 episodes of transient hypoxemia. Only five such episodes occurred in three of five "pink-puffer" patients. All "blue bloaters" with low basal mean SaO2 had multiple atrial and ventricular premature contractions and a high heart rate at rest; six patients has a prolonged QTc, three had ST-T depression, and one had right-bundle-branch block. Oxygen therapy increased basal mean SaO2, reduced ectopic activity, abolished ST-T changes and bundle-branch block, significantly reduced the resting heart rate and the amplitude of the R and S waves, and shortened the QTc in four nonsmokers. These results suggest that sustained hypoxemia contributes to myocardial dysfunction and heart failure in "blue-bloater" patients.

The efficacy of audiotape was compared with that of videotape as a way of teaching students the essentials of the medical interview. Two consultants--a general physician and a neurologist--were videotaped as they took histories from two patients. The neurologist described his methods and summarized his findings, but his interview was conducted conventionally without interruptions (continuous interview). In a contrasting style, the general physician frequently explained his methods and findings in steps, interrupting his interview to do this (discontinuous interview). Fifty students starting their main medical term were divided into two groups (A and B). Group A was shown the videotape of the discontinuous interview while group B was played an audiotape of that interview. Groups A and B were then crossed over, but this time group A was allowed only to hear the audiotape of the continuous interview, while the videotape of it was played to group B. After each tape the students were tested on its content. There was no significant difference between the mean scores of Group A and Group B when tested on the discontinuous interview and both groups scored well. For the continuous interview the group who saw the videotape scored significantly better than the group who only heard this tape. Both groups scored significantly better in the test based on the discontinuous interview than they did in the test based on the continuous interview. The results indicate that videotapes are a good medium for teaching history-taking, but also suggest that audiotape recordings of medical history-taking can be effective teaching aids if the interview is explained in stages.

Numerous studies have demonstrated that Na+/Li+ countertransport is increased in erythrocytes from hypertensive patients. Since Na+/Li+ countertransport is conducted through the physiologically occurring Na+/Na+ exchange, we studied the latter pathway in 20 subjects with essential hypertension and 20 normotensive subjects matched for age and sex. Ten hypertensives and six normotensives had a positive family history of hypertension. Ouabain (0.1 mM) and furosemide (0.1 mM) were used to assess the active Na+ efflux and Na+-K+-Cl- pathway. There was no significant difference between hypertensive and normotensive subjects in any of the three pathways studied. Among the 16 subjects with a positive family history of hypertension, the mean value for external Na+-dependent Na+/Na+ exchange was significantly higher than in 24 subjects with no family history of hypertension (0.0457 +/- 0.0337 versus 0.0283 +/- 0.0202; P less than 0.05). This study suggests that an inherited membrane transport defect may exist for Na+/Na+ exchange in families of hypertensive subjects.

We compared the antianginal efficacy of one conventional and three long acting beta-adrenoreceptor blocking agents in a randomised manner in 12 patients with stable angina pectoris. An exercise test was performed initially and in the 24th hour after a single daily dose of 160 mg of each beta-blocker at the end of a two week treatment period. In addition, glyceryl trinitrate consumption, anginal attack rate, and activity scores were recorded. No titration studies to an equivalent degree of beta-blockade were undertaken; a fixed dose was used even though these drugs are not equipotent. Conventional propranolol in a single daily dose of 160 mg was as effective in controlling the frequency of anginal attacks as long acting propranolol and sustained release oxprenolol. Exercise tolerance was less with sustained release oxprenolol than with conventional propranolol, long acting propranolol, and nadolol. Nadolol produced a significantly greater reduction in exercise-induced tachycardia than did long acting propranolol, sustained release oxprenolol, and conventional propranolol, and also the lowest anginal attack rate, the lowest trinitrin consumption, and significantly less ST segment depression than the other three. These findings suggest that nadolol is more potent than long acting propranolol, sustained release oxprenolol, and conventional propranolol, and the antianginal benefit at the 24th hour relates to the degree of beta-adrenoreceptor blockade achieved.

The relationships between intracellular sodium content, sodium transport and serum effects were investigated in human fibroblasts. In the cells with low intracellular sodium (Na+iL; 0.04 mumol sodium/mg protein), serum stimulated the sodium-potassium pump as measured by ouabain-sensitive sodium efflux and rubidium influx and also exerted a transstimulation of ouabain-insensitive sodium transport resulting in net influx. In cells with high intracellular sodium (Na+iH; 0.42 mumol sodium/mg protein) all aspects of sodium transport were increased compared to Na+iL cells. In these cells serum caused no change in sodium-potassium pump activity but significantly increased the ouabain-insensitive sodium fluxes resulting in net efflux. In Na+iL cells, serum promoted net sodium influx through an amiloride-sensitive pathway that was undetectable in the basal state. In Na+iH cells the serum-stimulated net efflux was amiloride sensitive but this pathway also contributed to a major portion of sodium transport in the basal state. This study demonstrated that sodium-potassium pump activity is directed by the supply of internal sodium and that serum can increase this supply by promoting net influx, and that serum-induced sodium transport can be modified by intracellular sodium content.

1. Previous studies have shown that leukaemic plasma inhibits sodium efflux from erythrocytes. In this study the effect of an extract of myeloid leukaemic blast cells on sodium efflux was investigated. 2. Blast cell extract decreased the sodium efflux rate constant in erythrocytes from 0.395 +/- sem 0.028 to 0.310 +/- 0.018 (P less than 0.02), whereas a leucocyte extract had no significant effect. 3. The extract had an inhibitory effect after heating at 80 degrees C for 30 min, and in the presence of ouabain and frusemide alone or in combination. 4. These studies suggest that myeloid leukaemic blast cells contain a heat stable factor which inhibits the efflux of sodium at least in part through a pathway which is not inhibited by ouabain or frusemide.

We studied the value of serum lysozyme as a helpful test in distinguising tuberculous involvement of intrathoracic glands from lymphoma. Nineteen of the 28 patients (all Asian immigrants) with intrathoracic glandular tuberculosis had raised serum lysozyme level as compared with 2 of the 29 patients with lymphoma. While a normal serum lysozyme level is unhelpful, a raised level in an Asian immigrant with hilar or mediastinal lymphadenopathy makes tuberculosis a highly probable diagnosis.

1. At a high dilution in Ringer solution (1:200), leukaemic plasma significantly (P less than 0.05) decreased the ouabain-sensitive and increased ouabain-insensitive components of sodium efflux from erythrocytes. At a low dilution (1:10) leukaemic plasma predominantly decreased the total and ouabain-insensitive component of sodium efflux (P less than 0.01). 2. Erythrocytes from patients with leukaemia had a high affinity for the plasma factor which inhibited the total and ouabain-insensitive efflux (inhibitory factor). 3. Washings of leukaemic erythrocytes which had been incubated in leukaemic plasma contained a factor which significantly decreased the ouabain-sensitive and increased ouabain-insensitive components of sodium efflux (the anti-ouabain-like factor). 4. These studies show that leukaemic blood contains two factors which have opposite effects on sodium efflux from erythrocytes. These factors may contribute to the high incidence of multiple electrolyte disturbances in acute myeloid leukaemia.

Combinations of 2 or 3 drugs are often used to treat angina pectoris, but their combined cardiorespiratory effects have not been investigated. Using a randomized, double-blind, placebo-controlled protocol, the effects of nadolol alone and nadolol in combination with isosorbide dinitrate and nifedipine were compared, in low and high doses, on antianginal efficacy, respiratory functions and arterial blood oxygen saturation (SaO2) in 19 patients with stable angina pectoris. A complete assessment including a bicycle exercise test with the measurement of the sum of ST-segment depression in all leads (sigma ST) was carried out every 2 weeks. The frequency of anginal attacks and nitroglycerin consumption was reduced significantly (p less than 0.001) by nadolol alone and in combination with the other drugs. Nadolol caused a slight reduction in the forced expiratory volume in 1 second, which was improved by isosorbide dinitrate and nifedipine. The sigma ST profile (basal, at peak exercise and 2 and 5 minutes after exercise) was decreased by nadolol alone and in combination with the other drugs, although the greatest reduction was achieved with large doses of nifedipine and nadolol. The rest and postexercise SaO2 decreased after nadolol alone and in combination with isosorbide dinitrate, but recovered to pretrial values after nifedipine and nadolol. With all drug combination, sigma ST depression was greater when the postexercise SaO2 was less than 92%, and decreased (p less than 0.05) in the same patients when their postexercise SaO2 was greater than 92%.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum lysozyme (muramidase) estimation is a simple, convenient and useful laboratory investigation. A review of the literature shows that lysozyme has been implicated as an aetiological factor in various disorders, and credited with being a prognostic indicator in acute myeloid leukaemia, but these promises have not been fulfilled. This low molecular weight protein is found in the urine of some patients with renal tubular disorders, but some workers have emphasized its importance as a causal agent in hypokalaemia of acute myeloid leukaemia. Research should be concentrated on muramidase as an expression of cell functions rather than as an aetiological factor. Hypokalaemia in acute myeloid leukaemia may be caused by an unidentified substance of molecular weight similar to that of lysozyme.

Hyponatraemia was observed in 11 out of 14 consecutive patients with acute myeloid leukaemia and its variants. Metabolic studies on these patients revealed an early increase in the urinary sodium excretion, negative free water clearance, and urine osmolality inappropriately higher than that of the serum. It is postulated that this syndrome is caused by a substance released from the primitive cells of the abnormal myeloid series.

Previous studies have shown that leukaemic immature cells, specifically promyelocytes but not mature leucocytes, contain and release an inhibitor of ouabain-insensitive sodium transport (inhibitin). In the present study, medium from cultured leukaemic promyelocytes significantly reduced the ouabain-insensitive sodium efflux from erythrocytes, whereas medium from the same cell line which had been made to differentiate did not have this effect. Culture medium from normal bone marrow cells (containing promyelocytes) also significantly (P less than 0.001) reduced ouabain-insensitive sodium efflux. These data suggest that inhibitin is secreted by primitive but not by mature leukaemic cells and normal bone marrow cells.

To study the effects of a low carbohydrate, isoenergetic diet on pulmonary physiology and sleep behavior, we measured pulmonary functions and respiratory gas exchange and carried out ambulatory electroencephalographic studies after a week's intake of isoenergetic diet containing only 50 g carbohydrate per day in 6 healthy female adult humans in a free-living condition. Compared with their normal intake, during the week of low carbohydrate intake there was a rise in the level of fasting plasma 3-hydroxybutyrate from 0.12 +/- 0.07 (mean +/- SD) to 1.01 +/- 0.40 mmol/L(P less than 0.01, paired t-test); a fall in serum bicarbonate from 26.2 +/- 0.75 to 25.0 +/- 1.41 mmol/L (P less than 0.05) and in serum chloride from 107 +/- 1.3 to 105 +/- 1.8 mmol/L (P less than 0.05). Serum urea rose from 4.3 +/- 0.71 to 5.7 +/- 0.70 mmol/L (P less than 0.01), and serum uric acid from 0.34 +/- 0.08 to 0.39 +/- 0.10 mmol/L (P less than 0.05). Functional residual capacity was increased from 2.07 +/- 0.35 to 2.26 +/- 0.34 L (P less than 0.01). Respiratory gas exchange ratio fell from 0.81 +/- 0.05 to 0.75 +/- 0.04 (P less than 0.05) and partial pressure of expired carbon dioxide reduced from 22 +/- 3.3 to 21 +/- 3.1 mmHg (P less than 0.05). There was a reduction in endogenous carbon dioxide production and arterial carbon dioxide tension. An analysis of ambulatory electroencephalogram showed that REM latency increased from 66 +/- 8 to 111 +/- 38 min (P less than 0.05), with no significant changes in sleep time and stages. These studies show that a low carbohydrate isoenergetic diet is tolerable, influences sleep behavior, reduces carbon dioxide production and respiratory gas exchange ratio, and may be therapeutically useful in patients with hypercapnic respiratory failure.

In this study we investigated whether the sodium transport inhibitor, inhibitin, originally isolated from leukemic promyelocytes, was also elaborated by some other neoplastic cells in culture. Like culture medium from the leukemic promyelocytes (HL60), the media from two other leukemic cell lines (erythroblasts K562 and monoblasts U937) also showed significant inhibitory activity on ouabain-insensitive sodium efflux rate constant in normal erythrocytes. Similarly, culture media from three neoplastic cell lines (H.Ep2, MRC5, and HX99) also showed significant inhibitin-like inhibitory activity. Using high-performance liquid chromatography to isolate inhibitin, culture media from HL60 and H.Ep2 cells were identically treated, and inhibitin isolated from H.Ep2 cells had the same retention time as that shown by promyelocyte inhibitin. H.Ep2 inhibitin reduced ouabain- and bumetanide-insensitive sodium efflux rate constant from 0.1510 +/- 0.0275 (SD) to 0.0988 +/- 0.0110 (P less than 0.005). Like promyelocyte inhibitin, H.Ep2 inhibitin reduced sodium efflux and influx by equivalent amounts suggesting thereby that it is a sodium/sodium exchange inhibitor. These studies show that a factor exhibiting inhibitory activity on sodium/sodium exchange is secreted by a variety of leukemic and neoplastic cells in culture.

Previous studies have shown that myeloid leukaemic blast cells contain a heat stable factor which inhibits bidirectional sodium transport in normal erythrocytes. This study was undertaken to establish whether leukaemic promyelocytes in culture secrete this factor. Two cell-lines of leukaemic promyelocytes (HL-60 and JR) were grown and culture media from both reduced significantly the ouabain-insensitive sodium efflux rate constant, whereas conditioned culture medium (incubated like the cells in culture) had no inhibitory effect. Promyelocyte extract reduced significantly (P less than 0.01) the total sodium efflux rate constant from 0.393 +/- 0.030 (SD) to 0.311 +/- 0.060, and ouabain-insensitive efflux rate constant from 0.131 +/- 0.008 to 0.079 +/- 0.009 (P less than 0.001). The inhibitory factor was heat stable (80 degrees C for 30 min) and it inhibited sodium efflux through a pathway which was not inhibited by ouabain or frusemide. These studies suggest that leukaemic promyelocytes secrete the previously identified passive sodium transport inhibitory factor.

Studies on erythrocyte sodium pump activity in obesity have yielded conflicting results probably because the erythrocyte is an atypical cell, and it may not reflect ATPase activity of other cells in the body. This study was undertaken to establish a reproducible procedure to measure sodium transport in human diploid fibroblasts, and apply this method to explore any differences in the cells from obese and nonobese humans. Cell cultures were established from 12 nonobese (body mass index (BMI) = wt in kg/height in m2 (Khosla and Lowe, Br J Prev Soc Med 1967; 21: 122-128); less than 27 kg/m2) and 10 obese (BMI) greater than 35 kg/m2) subjects. Triplicate measurements of sodium efflux rate constant were made with and without ouabain (1 mmol/l) to determine the total, active (ouabain-sensitive) and passive (ouabain-insensitive) components. Reproducible results were obtained as suggested by a coefficient of variation (CV) of less 10% on successive experiments on the same cell-line, and 11 and 15% of the active sodium efflux rate constant measured in fibroblasts from nonobese and obese subjects, respectively. The active sodium efflux rate constant in fibroblasts from nonobese (0.202 +/- 0.023 (SD)) was not significantly different from that obtained in the cells from obese subjects (0.21 +/- 0.030; p greater than 0.10). These results suggest that there is no intrinsic differences in basal sodium pump activity in fibroblasts related to obesity.

One hundred patients with proved tubercular synovitis of the knee were studied and 50 patients underwent inguinal lymph node biopsy. Results for and experience with lymph node biopsy in tubercular synovitis of the knee are presented.

The examination for membership of the Royal Colleges of Physicians has a high failure rate despite intensive clinical coaching provided by many postgraduate courses. One of the main difficulties appears to be the failure of candidates to identify specific shortcomings in their clinical behaviour. In this study videorecording was used as a method of self-appraisal enabling the candidate to identify strengths and weaknesses. The evidence from the study suggests that self-appraisal by videorecording should be used as an adjunct to clinical instruction.

The authors summarize their experience with 174 patients with aplastic anaemia (AA) with particular reference to course, prognostic factors, conversion to other blood disorders, treatment and outcome. Aplastic anaemia was defined as pancytopenia and a hypocellular marrow at some time during the illness. Seven patients terminated with acute leukaemia, 8 developed haematological features of sideroblastic anaemia and 5 showed a red cell membrane defect commonly found in paroxysmal noctural haemoglobinuria. Complete recovery occurred in only 4 patients; 70 others showed a partial remission with some residual haematological abnormality in peripheral blood. Eighteen of these had spontaneous remission. Remission was brief in 27 patients who died; only 32 patients remained in partial remission. Twenty-five per cent. of the patients with AA run an acute course and die within 6 months of the time of diagnosis. The remainder run a subacute or chronic course, punctuated in some cases by a transient remission, but in others by a conversion to other related haematological disorders. An acute course is suggested by a rapid onset of symptoms, a falling neutrophil count, a haemoglobin level less than 5 g/dl and a very low platelet count. A chronic course is likely in those patients who have a slow onset of symptoms, a stable neutrophil count and a Hb level in excess of 5 g/dl. The authors' experience shows that the disease runs either of the 2 courses irrespective of the supportive therapy.

An inhibitor of ouabain-insensitive sodium/sodium exchange in erythrocytes has been isolated from leukemic promyelocytes. To explore the specific effects of this inhibitor, named inhibitin, sodium transport experiments were carried out in human erythrocytes. Inhibitin reduced ouabain-insensitive bidirectional sodium transport. It did not change net sodium fluxes, had no significant effect on rubidium influx, and did not inhibit sodium-potassium-ATPase activity. The inhibitory effect of inhibitin was studied on sodium/sodium exchange and on sodium/lithium countertransport in 140 mM sodium and in sodium-free media. In the presence of sodium, inhibitin reduced sodium and lithium efflux to that observed in sodium-free medium. Inhibitin showed no reduction in sodium or lithium efflux when sodium was replaced by choline chloride or Mg2+. When inhibitin was combined with one or more of the other transport inhibitors (i.e., ouabain, furosemide, or bumetanide and amiloride), its inhibitable component remained distinct and it did not overlap with that of the other inhibitors. These studies show that inhibitin is a specific inhibitor of carrier-mediated sodium/sodium exchange and sodium/lithium countertransport processes in human erythrocytes.