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Background: Receiver operating characteristic (ROC) curve analysis provides detailed information about the performance of a diagnostic test., Methods and Results: As part of a multicenter phase III trial, 160 patients with known or suspected coronary artery disease underwent planar stress-rest 99mTc-labeled tetrofosmin and stress-redistribution 201Tl imaging within 14 days of each other, to compare the diagnostic accuracy of these imaging modalities by ROC curve analysis. Coronary arteriography was used as the reference standard and greater than 70% stenosis was considered significant. ROC curve analysis showed improved detection of coronary artery disease with 99mTc-labeled tetrofosmin compared with 201Tl, with ROC curve areas of 0.765 versus 0.644, respectively (p = 0.02). 99mTc-labeled tetrofosmin also better identified single-vessel disease in those without previous myocardial infarction (ROC curve areas of 0.684 vs 0.510 for 99mTc-labeled tetrofosmin and 201Tl, respectively; p = 0.04) and enhanced the detection of multivessel disease in those with previous myocardial infarction (ROC curve areas of 0.764 vs 0.638, respectively; p = 0.02)., Conclusions: Detailed assessment of diagnostic performance by ROC curve analysis shows that, for planar imaging, 99mTc-labeled tetrofosmin enhances the detection of coronary artery disease compared with 201Tl.

To investigate the therapeutic potential of increased plasma free fatty acid (FFA) and triglyceride concentrations in hypoglycaemic patients receiving quinine, 32 untreated Thai adults with uncomplicated falciparum malaria were allocated at random to one of 4 regimens: 2 mg/kg/min dextrose infused over 60 min either alone (group A) or with a prior injection of 5000 units of heparin and simultaneous Intralipid infusion (group C), or 4 min/kg/min dextrose alone (group B) or with heparin and Intralipid (group D). Quinine (10 mg/kg) was also infused over 60 min in all cases. In patients of groups A and C, mean changes in plasma glucose concentrations from the beginning to the end of the infusion were 0.1 (SD 0.8) and 1.0 (SD 0.7) mmol/L respectively (P = 0.015). In groups B and D, plasma glucose increased by 1.8 (SD 1.2) and 2.2 (SD 0.4) mmol/L respectively (P < 0.5). Plasma FFA levels fell by approximately 50% during the infusion in groups A and B but increased by a similar percentage in groups C and D. Despite significant mean increases in plasma insulin during the infusion (from 12.2 milliunits (mu)/L in group A to 38.8 mu/L in group D), no rebound hypoglycaemia was observed in any patient during the ensuing 7 h. These data suggest that the glycaemic response to dextrose given at high rates, which match average glucose utilization in a severely ill patient with malaria, is not augmented by increased plasma FFA and long-chain triglycerides. However, this strategy increases the glycaemic efficacy of lower dextrose infusion rates and the combination could, therefore, reduce the volumes of hypertonic dextrose required to prevent hypoglycaemia in severely ill patients in whom optimal fluid balance is crucial.

A new technique has been developed for measuring right ventricular function by nonimaging first pass ventriculography. The right ventricular ejection fraction (RVEF) obtained by non-imaging first pass ventriculography was compared with that obtained by gamma camera first pass and equilibrium ventriculography. The data has demonstrated that the correlation of RVEFs obtained by the nonimaging nuclear cardiac probe and by gamma camera first pass ventriculography in 15 subjects was comparable (r = 0.93). There was also a good correlation between RVEFs obtained by the nonimaging nuclear probe and by equilibrium gated blood pool studies in 33 subjects (r = 0.89). RVEF was significantly reduced in 15 patients with right ventricular and/or inferior myocardial infarction compared to normal subjects (28 +/- 9% v. 45 +/- 9%). The data suggests that nonimaging probes may be used for assessing right ventricular function accurately.

The results of indium-111 (111In) antimyosin imaging during life and the findings on postmortem imaging and triphenyl tetrazolium chloride (TTC) staining of the heart are reported from a patient who received 111In-antimyosin on the sixth day following myocardial infarction and died after imaging the next day. The planar images obtained during life showed abnormal 111In-antimyosin uptake in the posterior, lateral, and apical walls of the left ventricle. Autopsy revealed extensive infarction of the left ventricular lateral and posterior walls with cardiac rupture, which was the cause of sudden death. Direct imaging of the sliced specimen of heart revealed abnormal tracer uptake in the lateral and posterior walls of the left ventricle, which correlated closely with the area of necrosis outlined by TTC staining. Our results confirm the experimental findings that antimyosin antibody binds specifically to the acute irreversibly damaged myocardial cells. A high degree of tracer uptake can be seen even when 111In-antimyosin is injected six days postinfarction.

Patients with Graves' disease were studied for two years during and after a twelve-month course of treatment. Disease activity was determined by repeated measurements of thyroidal uptake of [99mTc]pertechnetate during tri-iodothyronine administration. These in-vivo measurements of thyroid stimulation were compared with the results of in-vitro assays of Graves, immunoglobulin (TSH binding inhibitory activity--TBIA). There was no correlation between the thyroid uptake and TBIA on diagnosis. Pertechnetate uptake and TBIA both declined during the twelve months of antithyroid therapy. TBIA was detectable in sera from 19 of the 27 patients at diagnosis; in 11 of these 19 patients there was a good correlation (p less than 0.05) throughout the course of their disease between the laboratory assay of the Graves, immunoglobulin and the thyroid uptake. Probability of recurrence can be assessed but sustained remission of Graves' disease after treatment cannot be predicted from either measurement alone or in combination.

At diagnosis there was no correlation between the uptake of pertechnetate by the thyroid and thyrotrophin receptor antibodies (TRAb) measured as TSH binding inhibitory immunoglobulins in a series of 27 patients with Graves' disease. TRAb were detectable initially in 19 patients, in 11 of these there was a significant positive correlation (P less than 0.05) between serial measurements of pertechnetate uptake and TRAb made during 2 years following diagnosis. In five patients pertechnetate uptake fell with time whilst TRAb levels were maintained or fluctuated. In the remaining three of the 19 patients both measurements were low and did not change during treatment. We conclude that TRAb in any individual patient are a mixture of immunoglobulins of variable effectiveness as thyroid stimulators. In a majority of patients the composition of this mixture remains constant during the course of the illness and the clinical state reflects the levels of TRAb in the blood. In a minority, however, the character of these antibodies may alter with time or there is a change in the responsiveness of the thyroid gland. The general lack of correlation between measurements of thyroid stimulating activity and TSH binding inhibitory immunoglobulins in groups of patients is due to differences between patients in the composition of TRAb.

Following the oral administration of 75Se-selenofolate in two normal healthy volunteers, retention was measured by whole body counting, and distribution throughout the body was determined with a hybrid scanner. Approximately 65% of the dose was absorbed from the GI tract. The metabolic data obtained from this study was used to calculate the integrated radiation dose to the liver, and the effective dose equivalent.

A simple radioisotope scanner was used in a study of liver diseases in The Gambia. Scans were of value in localizing areas for biopsy or aspiration and in defining the liver in the presence of gross ascites. Although the scan was not helpful in diagnosis it provided a measure of the size of filling defects during treatment.

A method of determining placental intervillous blood flow (IBF) using an inhaled 133Xe technique is described. The method was used to investigate the effect on IBF of epidural analgesia with an initial dose of 37.5 mg bupivacaine. There was no statistically significant reduction in IBF following the initial dose of bupivacaine in spite of a small but statistically significant reduction in mean blood pressure. There was no significant correlation between the change in mean blood pressure and the percentage change in IBF following epidural block although the single largest percentage reduction in IBF was associated with the largest fall in mean blood pressure.

Myocardial blood flow was measured by the 133Xe clearance technique in 21 patients 6 to 31 months after saphenous vein grafting for coronary arterial disease. Preoperative measurements were made in 16. All patients had improved symptomatically, and 20 had returned to work. Thirty of 39 grafts were entered and selective injections of 133Xe performed. Flow in the left coronary artery (LCA) was unchanged postoperatively in 9, increased in 5, and decreased in 1 (preoperative mean = 54 ml/100 g/min, SD +/- 16; postoperative mean = 65 ml/100 g/min, SD +/- 20). Flow in the right coronary artery (RCA) was unchanged postoperatively in 3, decreased in 9, and increased in 2 (preoperative mean = 46 ml/100 g/min, SD +/- 18; postoperative mean = 33 ml/100 g/min, SD +/- 12). Nine of 14 grafts to the left anterior descending coronary artery showed flow rates significantly greater than those in the corresponding LCA. Two of the 3 circumflex grafts showed flow rates significantly lower than those in the LCA. Four of 8 right grafts showed significantly higher flow rates than those in the corresponding RCA. These findings correlated well with the angiographic appearances. We conclude that saphenous vein grafting increases total myocardial blood flow. The data suggest that the coronary arteries and the grafts are supplying different regions of the myocardium, and that the graft regions were previously underperfused. There would appear to be little mixing of blood between artery and graft regions.

The nuclear probe was used for measuring left ventricular function in 11 normal subjects and the results compared with those using a digital gammacamera. The probe was then used to measure left ventricular function in patients with coronary artery disease during dynamic exercise and stress atrial pacing. The ability of the probe to detect changes induced by glyceryl trinitrate was also evaluated in separate parallel studies. In the 11 normal subjects there was a good correlation between the left ventricular ejection fraction measured by the gammacamera and the nuclear probe both at rest and during exercise. Exercise increased this value by at least 5% in all normal subjects during measurements with both the gammacamera and the nuclear probe. The mean (SD) difference was -0.3% (2.60) at rest and 2.3% (5.02) at peak exercise. Both exercise and pacing produced angina in the patient group and the mean (SEM) value fell from 52% (3.5) to 28% (2.6) and from 46% (5.1) to 34% (3.2) respectively. Glyceryl trinitrate prolonged the exercise and pacing times, and the corresponding falls in ejection fraction were significantly reduced. The non-imaging nuclear probe is a cheap and portable instrument capable of assessing left ventricular function in patients with cardiac disease. It is designed for high count rate acquisition over a short period of time and can thus provide both beat to beat and summated left ventricular time activity curves suitable for quantitative analysis. It therefore has important advantages in the clinical setting and during controlled interventions compared with the gammacameras.

The previously established direct relationship between long half-life of uncharged small unilamellar liposomes in the circulation of injected animals and reduced permeability to entrapped solutes in the presence of blood plasma was investigated further. It was found that vesicle size and surface charge override state of membrane permeability in determining rates of vesicle clearance. Thus, half-lives of liposomes that were practically impermeable in plasma were much shorter for larger vesicles or vesicles with a negative charge on their surface. 111In-labelled bleomycin-containing small unilamellar liposomes with long half-lives accumulated in the liver after injection to a much lesser extent (e.g., 26%) than similar liposomes (55% of the dose) exhibiting a shorter half-life. Much of the injected long-lived liposomes (about 35%) were recovered in the carcass of the animals. Scanning of the carcasses revealed quantitative accumulation of radioactivity in the bones, presumably the phagocytic cells of the bone marrow. Long-lived liposomes appear suitable for drug delivery to, or imaging of the bone marrow.

Two indices of alveolar epithelial permeability were derived in man by a non-invasive method. The rate of transfer of 99mTc DTPA (diethylenetriamine penta-acetate) from the lung into the blood was measured and a significantly greater (P less than 0.001) transfer rate was found in symptomless cigarette smokers compared with non-smokers.

1. A new method has been used to measure mean gastric transit time. 2. This method, based on the absorption of 24Na from the proximal small bowel, is simple, non-invasive and can be used at the bedside. 3. The mean transit time was increased by adding guar gum to a test meal. 4. There was a significant correlation between mean gastric emptying time and a subjective measure of satiety.

The variable clinical course of Graves' disease has been followed in 27 patients each studied for 2 years from the time of diagnosis. Thyroid hormone synthesis was blocked with large doses of antithyroid drugs for the first 12 months while euthyroidism was maintained with triiodothyronine. The latter was given alone from 12 to 18 months, and for the last 6 months the patients received no treatment. The activity of the disease was determined by repeated measurements of thyroid uptake of pertechnetate and by assay of thyrotrophin receptor antibodies (TSH binding inhibitory immunoglobulins). Retrospectively there were no features on presentation which singly or in combination indicated the clinical outcome: 16 patients remained in remission (Group 1) whilst in 11 hyperthyroidism had recurred before the end of the study (Group 2). Both measures of disease activity (thyroid uptake and antibody levels) fell during the first 12 months in patients of both groups. Recurrence of Graves' disease could be predicted in some but not all patients of Group 2 at 12 months by higher thyroid uptakes and levels of thyrotrophin receptor antibodies. There was, however, evidence of abnormal thyroid function, from which we infer continuing activity of the disease, 12 to 18 months after diagnosis in all patients of Group 1, even though these patients had normal TRH tests during the last phase of the study. The difference in the course of Graves' disease 12 to 24 months after diagnosis between those patients who remained in remission and those who did not was relative: in no patient was completely normal physiological control of thyroid function re-established. Clinical remission from hyperthyroidism at this time is a level of disease activity at which the normal physiological output of thyroid hormones is not exceeded.

A transportable apparatus for isotope renography, which allowed deconvolution analysis, was used to study the prevalence and prognosis of abnormalities associated with urinary schistosomiasis. Before carrying out studies in a heavily infected community, observations were made in a non-endemic area to allow derivation of criteria for abnormality. Comparison of the findings in the two areas showed that changes suggesting urinary tract obstruction were more common in the endemic area in subjects between nine and 45 years but not in older subjects. Measurements of effective renal plasma flow showed renal function was impaired in the endemic area in subjects older than 17 years but not in younger subjects. In the endemic area the results of renography were unrelated to the urinary egg count of the subjects examined, but there was an improvement in the abnormal renograms in a group of subjects aged between nine and 20 years who were re-examined a year after treatment with metrifonate. Follow-up data about 316 subjects was obtained two years after renography. Nine subjects had died, including four of the five subjects with abnormalities suggesting both obstruction and over-all loss of renal function. These findings, which are comparable to the results of similar studies using radiological techniques, suggest urinary schistosomiasis may be a significant cause of mortality in adults in intensely infected communities.

A miniature solid-state mercuric iodide (HgI2) nuclear probe detector has been developed in conjunction with a computerized nuclear probe (Nuclear Stethoscope) to enable continuous non-invasive monitoring of left ventricular function using 99Tc-labelled equilibrium blood pool techniques. Left ventricular ejection fraction was measured in 54 patients undergoing radionuclide angiography with a gamma-camera and with the Nuclear Stethoscope and a good correlation was obtained between both techniques (r = 0.94, n = 54, P less than 0.001). The prototype mercuric iodide detector was compared with the sodium iodide detector of the Nuclear Stethoscope and a study in 41 consecutive patients demonstrated a good correlation for the measurement of ejection fraction, ejection rate, peak filling rate and time to peak filling rate (r = 0.94, 0.89, 0.90 and 0.78 respectively). It may be possible to adapt the mercuric iodide detector for continuous non-invasive monitoring of left ventricular performance in critically ill patients and during physiological or pharmacological interventions.

Scalp blood flow and transcutaneous (tc) PO2 were measured in four fetal lambs at 130-135 days of gestation. Scalp blood flow was measured by the xenon clearance technique using a technetium source to correct for changes in distance from the detector. The effect of circular pressure, the so-called "tonsure effect" on scalp flow and tcPO2, was evaluated by pressing a ring on the scalp. A circular pressure between 20-30 mmHg markedly reduced local scalp blood flow and was sufficient to reduce tcPO2 to zero. We found evidence of significant recirculation of xenon in the fetal circulation indicating right-left shunting. This study showed that the tonsure effect seriously affected scalp blood flow and tcPO2 in the fetus.

The presence of a Baker's cyst may diminish the therapeutic effect of intra-articular 90Y treatment to the knee joint. SPECT (single photon emission computed tomography) was used in 10 patients with Baker's cysts, treated with intra-articular 90Y for persistent synovitis of the knee, to measure the amount of radioisotope within the cyst. Comparison was made with the arthrographic appearances. The likelihood or extent of uptake into Baker's cysts of 90Y injected into the synovial cavity of the knee was not predictable from arthrograms. Deposition of 90Y in cysts was variable, ranging from little or no measurable uptake to a substantial proportion of the administered activity (40% in one case out of 10). It did not appear to relate to clinical response. The low mean uptake (6.3%) in cysts of nine out of 10 patients was probably insignificant in view of the large uncertainty in the prediction of synovial radiation dose.

We report the development of a new method for obtaining right ventriculograms using the peripheral intravenous infusion of a new tracer, 127Xe dissolved in saline. This tracer has a half life of 36 days, emits 172 keV and 203 keV photons, and is completely cleared by the lungs during pulmonary transit. The right ventricle can therefore be imaged free from interfering activity in the systemic circulation. The technique was used in 11 normal subjects and the results compared with those obtained using first pass and gated equilibrium blood pool angiography with 99mTc. Excellent images of the right ventricle were obtained and the tricuspid and pulmonary valve planes could be easily identified. This imaging technique has significant advantages over existing methods for the noninvasive assessment of right ventricular function.

In a study comparing two regimens of treatment after intra-articular irradiation of the knee with yttrium-90 one group of patients was allocated to bed rest for 48 hours in hospital and the other to mobilisation at home. Initially a Robert-Jones orthopaedic bandage was applied to the knee in all patients, serving as a semi-rigid splint, but as loss of isotope from the knee was appreciable in the mobilised patients, subsequent patients were sent home with the knee in a plaster-of-Paris cylinder. No difference in extra-articular spread or chromosomal damage was found between the patients sent home with their knee in a rigid splint and those treated by bed rest. Clinical outcome at three months was satisfactory in all three groups. These results show that rigid splinting is essential in reducing extra-articular spread of the isotope but that bed rest is not necessary. Increases in intra-articular pressure associated with quadriceps muscle activity combined with flexion of the knee may be the most important factor affecting extra-articular spread of isotope.

Pulmonary uptake of thallium-201 during exercise was measured in 58 patients with coronary artery disease and compared with the results from 21 patients with normal coronary arteries and 5 normal volunteers. A quantitative method was used to assess the pulmonary thallium uptake relative to cardiac activity (heart/lung ratio). This ratio was calculated for exercise and for redistribution imaging. The mean exercise heart/lung ratio for the group with coronary artery disease was 1.43 +/- 0.36 SD (n = 58); and for the "normal" group was 2.76 +/- 0.41 (n = 26) (P less than 0.001). Increased pulmonary uptake after exercise in the coronary disease group was reversible (mean redistribution heart/lung = 1.96 +/- 0.37 SD; P less than 0.001). The exercise heart/lung ratio differed significantly between groups with single-, two- and three-vessel disease; patients with and without prior infarction; and patients with exercise-induced ST segment depression and elevation. Linear regression analysis between ejection fraction calculated from equilibrium radionuclide angiography at rest and the exercise heart/lung ratio in the coronary artery disease group gave the equation: exercise heart/lung = 0.857 +/- 0.014 ejection fraction for n = 58; r = 0.695; P less than 0.001. It would appear that the exercise heart/lung ratio is a simple and valuable non-invasive index which should be used as part of routine thallium scan interpretation to provide additional information on left ventricular function after exercise and as an indicator of the severity of obstructive coronary artery disease.

Twelve patients with a diagnosis of schizophrenia and thirteen control subjects were injected with 77Br-bromospiperone and scanned using single photon emission tomography after 16 h. Although a statistically significant increase in patients by comparison with controls could be demonstrated, wide variations in specific activity of the ligand preclude a firm conclusion. In two patients but no controls an asymmetry in striatal uptake was noted, the uptake on the left being less than that on the right.

A new 99mTc-phosphine-isocyanide complex with the general structure [99mTc (DEPE)2(CNR)2]+ has been synthesised and tested in animals and one human. In three animal species (rat, rabbit, dog), the complex is an efficient myocardial imaging agent, while in humans it remains in the blood pool. The complex is 100% protein bound in animals and humans, but whereas in humans it is attached to a 51.5 kdalton protein (probably prealbumin), in rabbits it appears to be bound to a larger macromolecule (M.W. greater than 100 kdalton). The efficiency of the complex for blood pool labelling was tested in a human volunteer and compared with the standard in vivo red cell labelling technique with stannous pyrophosphate. A satisfactory radionuclide angiogram could be performed with less than 370 MBq of the complex. The count rate for the complex (cps/MBq) was 15% higher than that obtained with the labelled red cells and the absence of splenic activity was notable. In humans this complex appears to be an efficient blood pool labelling agent which might be useful for radionuclide ventriculography.

Two regimens to immobilise the knee after injection were compared in patients receiving intra-articular yttrium-90 for persistent synovitis of the knee, the patients being randomly allocated to receive either complete bed rest or full mobilisation with the affected knee in a firm splint. There was no difference in the percentage of the radioisotope retained in the knee or in that taken up by other tissues between the two regimens. It is concluded that after intra-articular injections of yttrium-90 strict bed rest in hospital is unnecessary.

An adult with Gaucher's disease was injected with liposomes containing human glucocerebroside: beta-glucosidase. After 13 months of treatment the lower border of the right hepatic lobe and moved up 3 cm, and the left lobe had shrunk. Reduction in the size of the liver was associated with relief of pressure symptoms in the left lower abdomen. Scans obtained after the injection of radiolabelled liposomes suggested improvement in function of the reticuloendothelial system.

The characteristics of three colloidal preparations of 90-Y currently used for the irradiation of chronic synovitis of the knee have been studied. One, 99-Y silicate, showed less leakage away from the joint than the other two preparations, 90-Y ferric hydroxide and 90-Y citrate. Comparable amounts of 90-Y were taken up regional lymph nodes when the silicate and ferric hydroxide forms were used; the greatest irradiation of regional lymph-nodes occured using the citrate form. In this respect all three preparations are inferior to the previously used preparation 90-Y resin colloid which is no longer manufactured.

1. Renal function has been studied in 312 hypertensive patients by quantitative renography with sodium o-[131I]iodohippurate (131I-labelled Hippuran) and estimation of overall effective renal plasma flow. In 59% of the patients the results were normal. 2. Severe hypertension was associated not only with reduced effective renal plasma flow but also a characteristic abnormality of Hippuran transport in 10% of the patients in which there was a wider than normal variation in transit times of Hippuran through the kidney, which may reflect non-uniformity of reabsorption of filtrate by different groups of nephrons. 3. Plasma renin activity was higher in a group of 14 patients with multimodal transit time spectra than in a matched hypertensive control group, with very substantial overlap between the two groups. 4. The renographic abnormality was usually reversed by treatment.

The use of SPECT with Bremsstrahlung radiation has been investigated in studies on patients undergoing 90Y therapy for persistent synovitis of the knee. In particular, its value in the estimation of 90Y uptake into Baker's cysts was assessed and, to this end, realistic 'knee phantoms' were employed in order to calibrate for cysts of different size. Problems associated with the measurement of the extensive Bremsstrahlung spectrum and the estimation of cyst volume have been discussed. It is shown that, although the apparent volume of a cyst is markedly dependent on the chosen count rate threshold, volumes greater than about 30 ml can be estimated with reasonable accuracy using a threshold of 50%. The uptake of 90Y in cysts, measured on 3 occasions within the first 2 days in 10 patients, showed wide variation (0%-40%) between patients and was poorly related to the size of cysts on arthrograms and to the clinical response to therapy. In these studies, the ability to analyse SPECT slices provided a distinct advantage over planar imaging for discriminating between 90Y uptake in cysts and adjacent sites. Retention of 90Y in the total knee was also widely variable, with losses of 2%-38% observed 2 days after injection which, in general, were not fully accounted for by uptake in liver or lymph nodes. The changing distribution of 90Y colloid in the knee during the first two days, as observed in some patients, might explain part of the discrepancy.

One hundred and three patients who underwent coronary arteriography were studied by thallium imaging and the results analysed by Bayesian principles to assess the usefulness of semiquantitative stress thallium imaging for predicting the presence or absence of multivessel coronary disease. Significant disease was found in 80 patients, of whom 77 had abnormal thallium scans (sensitivity 96%). Thallium images were normal in 15 of 23 patients with no significant disease (specificity 65%). Multiple thallium segmental defects were found to be 90% sensitive and 65% specific for multivessel coronary artery disease and were present in 80% of patients with left main stem disease and in 93% of patients with triple vessel disease. A single thallium defect or normal scan excluded multivessel, left main, and triple vessel disease with 81%, 94%, and 91% predictive accuracy respectively. By Bayesian analysis the predictive accuracy for excluding multivessel disease was greater than 90% in patients with a pretest probability of multivessel disease of less than or equal to 40%. Coronary arteriography to exclude multivessel disease is therefore unnecessary in a high proportion of patients with known or suspected coronary artery disease.

Vasodilators, such as nitroglycerin, have been widely used in the treatment of acute and chronic heart failure for therapeutic manipulation of the venous and arterial circulations to improve left ventricular function. We have tested the efficacy of a new formulation for sustained release buccal delivery of nitroglycerin (biological life 5-6 hr) in 21 patients with severe congestive heart failure due to ischaemic cardiomyopathy using maximal treadmill exercise testing and radionuclide angiography. A single-blind placebo-controlled acute and an open chronic phase (4 weeks) of treatment were employed. The mean dose was 23.4 mg daily, and clinical assessment suggested significant improvement in 15 patients. The mean ejection fraction (placebo) of 14.1% +/- 1.6 SEM increased to 19.1% +/- 1.7 (acute) and to 21.6% +/- 1.7 (chronic treatment) (P less than 0.001; n = 16). The mean exercise time increased from 3.02 +/- 0.4 min (basal) to 5.95 +/- 0.6 min (chronic) (P less than 0.001). Segmental wall motion abnormality was shown to improve after treatment for 4 weeks. There were no major side effects. Nine patients were reassessed after 24 weeks on the same regimen; exercise time and left ventricular ejection fraction were similar to the 4-week period, thus demonstrating a sustained improvement in cardiac function and functional capacity. A worthwhile functional and objective haemodynamic improvement was demonstrated in these patients with severe chronic congestive heart failure. This mode of treatment may have useful therapeutic value in the management of patients with a wide range of ischaemic heart failure.

Gametes and zygotes of Acetabularia have been studied with the electron microscope. The two flagella of the gamete enter the cell obliquely and the roots run near the surface of the organism. No connexion between the eyespot and the flagella was found nor was there regular relationship between the two eyespots of the zygote. When zygotes were fixed some hours after fusion of the gametes the eyespots appeared to be within the same chloroplast.Some zygotes had two nuclei or dumb-bell shaped nuclei suggesting stages of fusion. The initial contact between nuclei appeared to be through a narrow gap formed by fusion of the two nuclear membranes.