Thyroid scintigraphy with time-coded aperture. Coded aperture imaging (CAI) and multiple-view pinhole imaging (MVPI) of the thyroid were compared in 19 patients to determine whether CAI's theoretical advantages of high resolution, high efficiency, freedom from distortion, accurate size representation, and tomographic presentation could be realized in the clinical setting, and to determine whether CAI offers any advantage over conventional MVPI. The coded aperture images were judged better than the pinhole images in five cases, equal in 13 cases, and worse in one case. The major problem with CAI was the long reconstruction time. Further development and an extended clinical trial appear warranted.


Thallium-201 myocardial imaging: a comparison of the redistribution and rest images. Forty-one patients with chest pain and suspected coronary artery disease underwent thallium-201 myocardial imaging, performed immediately following maximal treadmill exercise, also at "redistribution" 4--5 hr after exercise, and at rest 1 wk later. All had coronary angiography. All images in seven patients without coronary artery disease were normal. Twenty-seven of the 34 (79%) patients with coronary artery disease had new, exercise-induced image defects. The redistribution and rest images were identical in 15/27 (56%) patients (complete redistribution). In 10/27 (37%) patients with exercise-induced defects, some redistribution occurred but defect size on the redistribution image was larger than that on the rest images (incomplete redistribution). In 2/27 (7%) of patients with exercise-induced defects, redistribution was absent. The presence of prior myocardial infarction, regional abnormalities of left-ventricular contraction or the severity of coronary stenoses did not correlate with the presence or absence of redistribution. Overall image quality between the two studies was similar, although image collection times for the redistribution study were prolonged. We conclude that some redistribution (complete or incomplete) occurs in most patients with exercise-induced image defects. When both fixed and reversible perfusion defects are present, defect size was often larger in the redistribution image and may thus overestimate the extent of prior myocardial infarction.


Validity of left-ventricular ejection fractions measured at rest and peak exercise by equilibrium radionuclide angiography using short acquisition times. To validate ejection fraction (EF) calculations from 5 and 2 minutes of multiple-gated equilibrium radionuclide angiographic data and to establish its utility during alterations in cardiac performance, we studied 38 patients with chest pain suggestive of coronary artery disease. Twenty-four patients underwent contrast ventriculography (CV) as well as first-pass (FP) and equilibrium (EQ) radionuclide angiography at rest, and 14 additional patients had both radionuclide tests performed at rest as well as during peak supine bicycle exercise. The resting 5-min acquisition ejection fractions were compared between each method and the following correlations were generated: r = .92, n = 24 (CV-EQ), r = .92, n = 24 (CV-FP), and r = .95, n = 38 (FP-EQ). The variability of EQ-EF calculations between two independent observers was less than 2%; the mean absolute difference between two sequential 2-min acquisitions and the 5-min recordings was -.1 +/- 1.6%, and the reproducibility of sequential 2-min ejection fractions was excellent (r = .98). EQ and FP ejection fractions at symptom-limited exercise correlated well (r = .96, n = 14). We conclude that equilibrium radionuclide angiography is a valid method to measure EF both at rest as well as during peak exercise even when 2-min acquisition periods are used.


Reproducibility of ejection-fraction determinations by equilibrium radionuclide angiography in response to supine bicycle exercise: concise communication. Sixteen patients with stable, chronic coronary artery disease were studied twice within and average of 15 days to evaluate the reproducibility of ejection fraction (EF) determined by equilibrium radionuclide angiography (EQ) at rest, during supine bicycle exercise (ex), and in the recovery period (rec). Following injection of 20--25 mCi of Tc-99m-tagged human serum albumin, data were analyzed for 2-min periods at rest, during several stages of exercise (submax, max), and during recovery (rec1 = minutes 2 + 3, rec2 = minutes 9 + 10). Each patient reached similar (heart rate) X (blood pressure) products in the two studies: 21280 +/- 5200 compared with 20390 +/- 4140 mmHg/min. Mean EFs for the first and second studies were: at rest (53.0 +/- 10.8)%, 52.5 +/- 10.4)% (r = 0.95; submax ex (51.4 +/- 12.0)%, (52.1 +/- 12.8)%, (r = 0.91); max ex (50.6 +/- 12.6)%, (51.6 +/- 12.9)% (r = 0.97); rec1 (62.7 +/- 11.6)%, (62.4 +/- 12.2)% (r = 0.95); rec2 (55.5 %/- 10.8)%, (57.2 +/- 11.7)% (r = 0.91). In stable patients, the reproducibility of EF determined by EQ is excellent during rest, supine bicycle exercise, and recovery from exercise.


Deconvolution analysis in radionuclide quantitation of left-to-right cardiac shunts. A poor bolus injection results in an unsatisfactory quantitative radionuclide angiocardiogram in as many as 20% of children with possible, left-to-right (L-R) cardiac shunts. Deconvolution analysis was applied to similar studies in experimental animals to determine whether dependence on the input bolus could be minimized. Repeated good-bolus, prolonged (greater than 2.5 sec), or multiple-peak injections were made in four normal dogs and seven dogs with surgically created atrial septal defects (ASD). QP/QS was determined using the gamma function. The mean QP/QS from ten good-bolus studies in each animal was used as the standard for comparison. In five trials in normal animals, where a prolonged or double-peak bolus led to a shunt calculation (QP/QS greater than 1.2 : 1), deconvolution resulted in QP/QS = 1.0. Deconvolution improved shunt quantitation in eight of ten trials in animals that received a prolonged bolus. The correlation between the reference QP/QS and the QP/QS calculated from uncorrected bad bolus studies was only 0.39 (p greater than 0.20). After deconvolution using a low pass filter, the correlation improved significantly (r = 0.77, p less than 0.01). The technique gave inconsistent results with multiple-peak bolus injections. Deconvolution analysis in these studies is useful in preventing normals from being classified as shunts, and in improving shunt quantitation after a prolonged bolus. Clinical testing of this technique in children with suspected L-R shunts seems warranted.


Adrenal hemorrhage in the newborn: scintigraphic diagnosis. Four neonates with abdominal masses following adrenal hemorrhages were investigated by renal scintigraphy. Characteristic photon-deficient lesions were noted in the suprarenal areas during the phase of whole-body radionuclide distribution.


Scintigraphic imaging with tantalum-178 and the Anger scintillation camera: concise communication. Tantalum-178 is a short-liver radionuclide (T 1/2 = 9.3 min.) and emits primarily 56- to 64-keV characteristic x-rays. We have determined the imaging characteristics with this radionuclide and a large-field-of-view Anger camera. With a pinhole collimator, good spatial resolution is possible with Ta-178, although the image quality is superior with Tc-99m under comparable conditions. Spatial resolution with parallel-hole or converging collimators was much less satisfactory with Ta-178 because of septal penetration by high-energy photons. Pulmonary perfusion and liver-spleen images of excellent quality were obtained in the rabbit using the pinhole collimator and Ta-178-labeled agents.


Growth-hormone and somatostatin effects on [75Se]selenomethionine uptake by the pancreas. The imaging of the pancreas with [75Se]selenomethionine has a low rate of reliability. This study was carried out in order to elucidate some factors that may be important in affecting the degree of uptake of the tracer by the pancreas. Studies were carried out in animals to observe the effects of growth-hormone (GH), somotostatin (SRIF), L-DOPA, and apomorphine administration on the distribution of [75Se]selenomethionine. Intravenously administered GH significantly depressed pancreatic uptake of Se-75 in mice and dogs and depressed the pancreas-to-liver concentration ratio (P/L). The effect of i.p. GH in mice was to decrease the P/L ratio, but the decrease in pancreatic uptake was not statistically significant. There was also a greater effect of GH in dogs than in mice, with pancreatic uptake decreasing from 5.60 +/- 2.17% to 1.24 +/- 0.96% and the P/L from 4.78 +/- 1.85 to 0.97 +/- 0.73. L-DOPA and apomorphine produced effects similar to GH in mice. SRIF in small doses had little effect, but in larger doses it enhanced pancreatic uptake, although not affecting P/L. The results indicate that hypothalamic factors may be important in affecting the function of the exocrine pancreas. Both L-DOPA and apomorphine are known to stimulate GH production through hypothalamic-pituitary pathways. In addition to suppressing GH release, SRIF may have direct effects on the exocrine pancreas.


A dynamic phantom for radionuclide cardiology. A flow-based phantom has been developed to verify analysis routines most frequently employed in clinical radionuclide cardiology. Ejection-fraction studies by first-pass or equilibrium techniques are simulated, as well as assessment of shunts and cardiac output. This hydraulic phantom, with its valve-selectable dysfunctions, offers a greater role in training than in quality control, as originally intended.


Comparison of Xe-133 washout and single-breath imaging for the detection of ventilation abnormalities. The Xe-133 ventilation studies of 115 patients were analyzed to determine the relative abilities of the single-breath and washout phases to detect regional ventilation abnormalities. All Xe-133 images were obtained in the posterior projection before 6-view perfusion studies with Tc-99m human albumin microspheres. There were 275 regions with matching V-P abnormalities in the patients. The washout portion of the study detected 258 of these regions (94%) and the single breath detected 175 (64%) (p less than 0.01). The discrepancies were confined to regions with nonsegmental perfusion defects, where the single breath detected 139 matches and the washout 216. The discrimination ratio between normal areas and areas of obstructive lung disease improved from 2 to 1 after 1 min washout to 30 to 1 after 5 min. The late phases of Xe-133 washout are useful in detecting ventilation abnormalities, especially those associated with nonsegmental perfusion defects.


Noninvasive estimation of pulmonary arterial pressure by analysis of pulmonary blood-flow distribution. To determine whether a correlation exists between pulmonary arterial (PA) pressure (Pa) and the distribution of pulmonary blood flow, this distribution was measured in four upright dogs in the control state and during intravenous infusions of epinephrine or prostaglandin F2 alpha. During suspension of respiration, 15 mCi of Xe-133 were injected intravenously, and perfusion and equilibration lung images were recorded with a scintillation camera. The procedure was performed several times on each dog, with and without pharmacological elevation of PA pressure by 5 to 50 cm H2O. For each scintigram, the relative blood flow per unit ventilated lung volume (F) was plotted against centimeters above the hilum (h). Pulmonary arterial pressure was derived from each curve, assuming the relation F = B(Pa - hD)2, where B = constant and D = specific gravity of blood. Calculated PA pressure correlated strongly (r = 0.83) with measured PA pressure, suggesting a possible means of noninvasive estimation of PA pressure.


Serial TSH determination after T3 withdrawal or thyroidectomy in the therapy of thyroid carcinoma. Exogenous triiodothyronine (T3) was substituted for levothyroxin or desiccated thyroid in 13 athyrotic patients previously treated for papillary, follicular, or mixed papillary-follicular carcinoma of the thyroid. After 4 weeks T3 therapy was discontinued and serial determinations of plasma thyroid stimulating hormone (TSH) concentrations were made. A roughly exponential rise in TSH values, corresponding to a doubling time of 2 days, was observed until a level of 40 microIU/ml was reached, after which the curve passed through a maximum at 20 days. The mean time required for a level of 50 microIU/ml was 11 days, and this time is suggested for TSH determination before I-131 imaging of patients with thyroid cancer. Plasma TSH values in eight patients following "total" thyroidectomy showed a much slower and more variable rise, with a mean doubling time of 7.6 days. Weekly TSH levels beginning at 15 days will provide a rational basis for I-131 imaging in this group, in whom a longer period of hypothyroidism will be required before imaging and therapy. Adherence to these protocols should minimize the duration of hypothyroidism in patients undergoing I-131 treatment of thyroid carcinoma.


A comparison of two technetium-99m-labeled radiopharmaceuticals for lymphoscintigraphy: concise communication. A comparison of stannous phytate and antimony sulfide colloid, both labeled with Tc-99m, was conducted during the performance of internal mammary lymphoscintigraphy in 46 patients. Thirteen of these patients were randomized to receive both radiotracers in two consecutive studies. The results indicated a statistical difference between agents; Tc-99m antimony sulfide allowed visualization of a greater number of more intense nodes, better delineation of the total length of the internal mammary lymph-node chain, and a more consistent visualization of supraclavicular nodes. Although previously published animal data suggest utility of Tc-99m stannous phytate for lymph-node imaging, Tc-99m antimony sulfide was shown in this clinical comparison to provide a more reliable representation of lymph-node anatomy.


Effect of food intake on the tissue distribution of gallium-67: concise communication. Fasting affects the body retention and tissue distribution of Ga-67 in experimental animals. In Ga-67 experiments, therefore, a difference in food intake between treated and control animals might result in confusing side effects. We have observed this in irradiation studies. It is suggested that a fasting regimen should be imposed in any Ga-67 animal study where an alteration in food intake might be experienced in the treated group.


Kinetics of the human thyroid trap: effects of iodide, thyrotropin, and propylthiouracil. Effects on the thyroidal pertechnetate trap of iodide, thyrotropin (TSH), and propylthiouracil (PTU), compared with duplicated control studies, were assessed in normal subjects using i.v. [Tc99m] pertechnetate, a multicrystal scintillation camera, and a compartmental model. Sodium iodide (1 g), administered orally on two occasions, 2 wk apart, caused an early drop in plasma clearance into the follicular cell (p less than 0.05), with later return to normal clearance 1 wk after the second NaI dose. In this later study, exit from the colloid was elevated (p less than 0.01). Plasma equivalent volume of the "colloid" compartment was reduced in both postiodine studies (p less than 0.05). Thyrotropin, 10 units intramuscularly, was followed by no significant changes in trap parameters at 2 hr. At 24 hr, plasma clearance had doubled (p less than 0.05), and the plasma equivalent "colloid" volume had tripled (p less than 0.01). Propylthiouracil was given as a single 1 g dose 1 hr before a trapping study followed by 200 mg PTU every 8 hr for 1 wk. The first dose resulted in apparent reduction in all of the rate constants for transport across the basal and apical thyroid follicular cell membranes; these rates returned toward control levels after 1 wk. The plasma equivalent "follicular cell" volume was reduced to 66% of controls levels (p less than 0.025) after 1 wk PTU. These effects must be taken into account in the interpretation of studies of the trap based on PTU pretreatment to inhibit organification.


Effects of isoproterenol on distribution of perfusion in embolized dog lungs. In 19 mechanically venilated, anesthetized dogs, autologous venous thrombi were formed in the inferior vena cava and subsequently released. Serial perfusion lung scintigrams revealed the postembolic distribution of pulmonary blood flow before, during, and after the infusion of isoproterenol at 2.2 micrograms/min. Isoproterenol failed to restore perfusion to embolically occluded regions. When reperfusion occurred it was attributable to clot resolution. Gas exchange and hemodynamic measurements obtained in seven thromboembolized animals showed no scan evidence of reperfusion during the isoproterenol infusion. After embolization, cardiac output increased from 1.7 to 2.6 liter/min (p less than 0.05), and PvO2 from 38.0 to 45.3 mm Hg (p less than 0.05). Shunt fraction remained unchanged. The postembolic infusion of isoproterenol was associated with a further increase in cardiac output to 3.6 liter/min (p less than 0.01), an elevation in PvO2 to 50.7 mm Hg, along with a decrease in pulmonary vascular resistance from the postembolic mean of 448 to 246 dynes.sec.cm-5 (p less than 0.05). Perfusion defects following acute pulmonary thromboembolization are not altered by the infusion of the potent pulmonary vasodilator, isoproterenol. Infusion of this drug following thromboembolization may have potential therapeutic benefit by reducing pulmonary vascular resistance, increasing cardiac output, and elevating the mixed-venous oxygen tension.


Radioimmunoassay of free thyroxine with prebound anti-T4 microcapsules. Free thyroxine (FT4) may be one of the active throid hormones in contact with target end organs. It is unaffected by alterations in serum protein levels. In most cases, measurement of FT4 reflects an individual's true thyroid function or dysfunction. Previous FT4 assay techniques have been difficult, tedious, indirect, and inaccurate. A rapid, simple, and accurate radioimmunoassay for FT4 has been developed using microencapsulated rabbit anti-T4 antiserum to which I-125 T4 tracer of high specific activity has been complexed. Addition of FT4 standards or unknown samples displaces a proportional amount of I-125 T4 from antibody. Protein-bound T4 is excluded from the reaction by short incubation time and spatial configurations. Specimens representing known thyroid dysfunction were tested using the above procedure. The normal range of FT4 was 0.8-2.4 ng/dl. The mean FT4 for the hyperthyroid group was 6.92 +/- 1.38 (range 4.4-9.6) ng/dl. The mean FT4 for the hypothyroid group was 0.43 +/- 0.37 (range 0.1-1.3) ng/dl, and in pregnancy the mean FT4 was 1.64 +/- 0.44 (range of 1.0-2.2) ng/dl (1).


Evaluation and application of alumina-based Rb-82 generators charged with high levels of Sr-82/85. Generator-produced Rb-82, a 75-sec positron emitter with potential for myocardial blood-flow imaging, was studied with various ion-exchange columns to evaluate the characteristics of alumina as an adsorber for the 25-day Sr-82 parent. Test columns of alumina, Bio Rex 70, and Chelex 100 were loaded with multimillicurie amounts of no-carrier-added Sr-82/Sr-85 (Sr-85 is a production contaminant). The breakthrough of Sr-82/Sr-85, and the yield of Rb-82, were determined for long-term elutions from each column with up to 4 liter of 2% NaCl solution at pH 8 to 9. The breakthrough of Sr-82/85 was 10(-6)-10(-5) from aluminal 10(-6)-10(-4) from Chelex 100 and Bio Rex 70. The effects of eluent flow rate and concentration, and of alumina volume, on the breakthrough and yield were also studied. An improved and automated Rb-82 generator was used for myocardial and brain blood-flow studies in experimental animals and in man; it was equipped with solenoid flow-control valves and five in. of lead shielding for the alumina columns, which were charged with 25-50 mCi Sr-82 (100-150 mCi Sr-85). The Rb-82 generator with alumina column provided up to 20-40 mCi of Rb-82 as often as every 5-10 min with less than 10(-5) breakthrough of Sr-82/85 over the 2- to 3-mo, useful life of the generator.


Accumulation of radioiodinated L-alpha-methyltyrosine in pancreas of mice: concise communication. L-3-iodo-alpha-methyltyrosine, labeled with either I-131 or I-123, has a high pancreatic specificity in mice. A pancreas-to-liver ratio of 8.6 +/- 2.7 is observed during the first hour after i.v. injection. Accumulation is also prominent in the kidneys, but excretion of the radioagent is rapid, 50% of the activity being eliminated during 90 min. Compared with L-[75Se]selenomethionine, the compound currently used for pancreatic imaging, L-3-[123I]or[131I]iodo-alpha-methyltyrosine has a higher pancreas-to-liver ratio, a shorter physical half-life and biological half-time, and better decay characteristics.


Effects of a reduction in crystal thickness on Anger-camera performance. The performances of two commerical gamma cameras, with crystals 1.3 and 0.6 cm thick, are compared. Phantom studies simulating clinical conditions showed no significant difference in performance at 140 keV. At 68 keV, the thinner crystal gave marginal improvements in camera performance with phantoms simulating clinical conditions. Frequent use with very low-energy emitters, such as Tl-201, would be needed to justify the expense required to refit the 1.3 cm camera with a 0.6 cm crystal.


A technique for measurement of xenon-133 air contamination. A sensitive, inexpensive technique is described for measuring xenon-133 air contamination to levels below nonoccupational exposure limits. The method uses a column containing a measured amount of activated charcoal through which an air sample is passed. The relative effects of air flow rate, xenon concentration, air temperature, relative humidity, and characoal weight on the amount of trapped xenon are described.


Hepatitis B: an occupational hazard of health care facilities. Hepatitis B is recognized as a major health hazard to hospital personnel. During a four-year period, 30 cases of hepatitis B were attributed to work at an urban medical center. Only four of these 30 individuals described a relevant accident in advance of their hepatitis and five others retrospectively suggested a specific episode that might have accounted for their illness. Early symptoms of the illness were nonspecific and routine monitoring and clinical awareness are necessary for early diagnosis. All employees recuperated from their acute hepatitis, but one developed chronic active hepatitis. The incidence and morbidity of the disease emphasize the need for more effective control measures. The inconspicuous exposures responsible for the illnesses observed render it unlikely that any postexposure immune globulin prophylaxis will suffice in further reducing the incidence of hepatitis B.


Cancer mortality among beekeepers.

Cancer mortality among beekeepers. Carcinogenic effects of bee venom were evaluated in a mortality study of 580 occupationally exposed beekeepers. The subjects were identified through obituary notices published between 1949 and 1978 in three journals of the U.S. beekeeping industry. Death certificates of beekeepers were examined for causes of mortality, and proportionate mortality ratios were compared with those for the general U.S. population. Beekeepers had a slightly lower than expected fraction of deaths from cancer. The deficit of lung cancers in male beekeepers was significant (p less than 0.05) and may indicate that fewer beekeepers were cigarette smokers. The frequencies of other cancers did not differ significantly from expectation. Non-Hodgkin lymphoma developed in four persons, and was expected in two. Mortality from diseases other than cancer showed no unusual patterns. At least two persons died from accidents directly related to the care of beehives. Analysis of a subgroup of 377 males with major roles in the beekeeping industry showed no substantial differences in distribution of causes of death. This study of beekeepers reveals neither adverse nor beneficial effects of intense exposure to bee stings.


Detecting non-valid hearing tests in industry. As greater numbers of workers come under industrial hearing conservation programs, the problem of nonorganic hearing loss is become critical. The potential malingerer can be identified by behavioral observations both before and during the testing of hearing and by an analysis of test results. Manual, self-recording, and microprocessor audiometry all incorporate validity and reliability checks which assist in detecting the malingerer. Methods of documenting inaccurate hearing tests are detailed, along with ways of obtaining accurate follow-up tests. The key to alleviating the problem of malingering is early detection and immediate resolution of the problem.


Airway responsiveness in workers processing polyester resins. In 22 employees of a button-manufacturing plant, exposure to polyester resins over an eight-hour work shift resulted in an acute reduction of flow rates on maximum expiratory flow volume (MEFV) curves at MEF50% and MEF25%. In the workers studied, preshift administration of 80 mg of propranolol potentiated, while 1 mg of subcutaneously injected atropine significantly inhibited, the bronchoconstricting effect of the resins, indicating that the autonomic nervous system plays an important role in determining airway smooth muscle response to polyester resins. Although a high prevalence of acute symptoms (cough, shortness of breath, throat and eye irritation) over the work shift was recorded in exposed workers, no high prevalence of chronic respiratory symptoms was found. No definite evidence of chronic airway obstruction was recorded in exposed workers.


Predictions of an inhomogeneous model: detection of local and extended spatial stimuli. A two-dimensional spatially inhomogeneous model of the visual system is developed. It is based on the properties of cone spacing in the retina and on the hypothesis of uniform neural interactions (lateral inhibitions). Its quantitative predictions of the detection and discrimination (acuity) of various types of stimuli are studied. The model works well with local stimuli positioned at varied eccentricities as well as with extended stimuli (vertical cosine gratings windowed by two-dimensional windows), but a simple threshold detector was found to be insufficient to describe the increase of contrast sensitivity with the number of cycles of the cosine gratings at high frequencies. It is concluded that, even for one-dimensional stimuli, a two-dimensional approach is necessary and that other parameters such as imprecision of fixation, eye movements, and two-dimensional probability summation must be taken into account before resorting to more complex models.


Bezold-brücke phenomenon of the extrafoveal retina. With the use of an asymmetric matching technique, the Bezold-Brück phenomenon of the extrafoveal retina was measured at different eccentricities during the cone-plateau period of the long-term dark-adaptation curve and after 30 min dark adaptation. The results indicate that both the rod and the cone mechanisms contribute to the luminance-dependent hue shift of the extrafoveal retina.


Rod-cone interrelationships at light onset and offset. The spatial constraints needed to obtain rod-cone interaction under steady adaptation levels apply to transient conditions of adaptation. The influence of cones upon rod threshold, however, is qualitatively different at light onset as opposed to light offset.


Electron microscopic changes in human oesophageal epithelium in oesophagitis. At the ultrastructural level the inflamed oesophageal epithelium shows a variety of lesions. These include mitochondrial damage, intracellular oedema, membrane whorls and dilation of the endoplasmic reticulum and the appearance of keratohyaline and parakeratosis granules. The basement membrane shows changes ranging from thickening to areas of loss of continuity. There is an increase in the anchoring fibrils. The spaces between the cells are enlarged and contain varying amounts of debris rich in neutral mucosubstances. There are less membrane-coated granules in the inflamed epithelium than in the normal. The intra-epithelial intrusive cells demonstrated were lymphocytes and neutrophil polymorphs.


Experimental granulomatous inflammation: the ultrastructure of the granuloma induced by injection of tubercle bacilli into Freund adjuvant-sensitised guinea-pigs. Injection of killed tubercle bacilli into a sensitised guinea pig produces a characteristic biphasic response with the development of an organised epithelioid cell granuloma in the second phase. Previous sensitisation to tubercle bacilli is a requirement for development of the organised granulomatous response. The main components of the granuloma are epithelioid cells, although multinucleate cells of both Langhans and foreign-body type are present. Epithelioid cells appear to evolve from monocytes, probably in the sequence: (a) monocyte, (b) monocytic transition form, (c) immature epithelioid cell, (d) mature epithelioid cell, although some may possibly develop through a macrophage stage. Differentiation of monocytes into epithelioid cells is a continual process in the experimental tuberculous granuloma with monocytes migrating into the lesion at all stages examined. Epithelioid cells are not obviously phagocytic. Their differ4ntiation has a phase suggestive of biosynthesis during which RER is the predominant cytoplasmic component. This is followed by a storage/secretory phase in which the cytoplasm contains membrane-lined vesicles and prominent Golgi apparatus. The vesicles and, where distended, the RER laminae contain a lightly staining, finely granular material the biological activity of which is unknown.


The resting membrane potential of frog sartorius muscle. 1. The absolute resting membrane potential of the frog sartorius muscle was determined in Ringer solution at 20 degrees C. 2. Membrane potentials were measured with 0.03, 0.1, 0.3, 1.0 and 3.0 M-KCl electrodes; potentials, including the micro-electrode-tip potentials, were -62.4, -75.7, -83.0, -87.7 and -90.7 mV respectively. 3. Membrane potentials were corrected for the liquid junction potentials between the Ringer and KCl solutions, and the myoplasm and the KCl solutions of the micro-electrodes, using the Henderson's liquid junction equation. 4. The cation (U) and anion (V) conductances of the myoplasm were adjusted to give a constant membrane potential after correction for liquid junction potentials. The final values for U and V were 5.6 and 1.3 mmho/cm respectively, resulting in a membrane potential of -93.0 mV. 5. The correction for the liquid junction potential was -2.6 mV when a 3 M-KCl micro-electrode was used.


The choice of models relating tritiated water absorption to subepithelial blood flow in the rumen of sheep. 1. The blood flow to the ruminoreticulum of anaesthetized sheep was varied by changing the proportion of CO2 in the gas stirring solutions confined to this organ. 2. Clearance of tritiated water was thereby varied fourfold, from 10 to 44ml./min.100 g epithelium, with negligible net water movement. 4. Subepithelial blood flow, observed with radioactive microspheres using the reference organ technique, varied tenfold, from 20 to 200 ml./min.100 g epithelium. 4. The relation between tritiated water absorption and blood water flow was approximated by a hyperbolic model, but was appreciably better described using a higher order term in blood flow consistent with a countercurrent exchange of tritiated water between arterioles and venules. 5. The distribution of blood flow between different regions of the organ and between epithelium and muscle is described.


Studies on the excitability of sinus nerve afferent terminals. 1. The excitability of sinus nerve afferent terminals within the nucleus of the tractus solitarius has been studied in cats and rabbits using the technique of antidromic activation. 2. Conditioning stimuli to the hypothalamic defence area increased the excitability of some glossopharyngeal nerve afferents, though no such effects were observed on sinus nerve terminals. 3. Although the excitability of superior laryngeal nerve afferent terminals was observed to fluctuate in phase with the central respiratory cycle, no equivalent variation in sinus nerve terminal excitability were observed. 4. It is concluded that sinus nerve afferent terminals are not influenced by presynaptic mechanisms. Possible sites for the observed modulations of baroreceptor and chemoreceptor reflexes are discussed in the light of these results.


Measurement and significance of the reversal potential for the pace-maker current (iK2) in sheep Purkinje fibres. 1. The apparent reversal potential (Erev) of the pace-maker current (iK2) is found to depend on the experimental protocol used for its measurement. Evidence is presented showing that depolarizing (hyperpolarizing) pulses given before a test hyperpolarization used to determine Erev, shift Erev to more negative (positive) values. These shifts are opposite to those expected if the only effect of pre-pulses were to change the concentration of potassium in extracellular clefts ([K]c) via accumulation and depletion processes. 2. This effect is shown to be due to the fact that Erev is dependent on s0, the degree of activation of iK2 at the start of the test hyperpolarization. 3. When a suitable protocol is used, depletion of cleft K can be demonstrated to take place during a large hyperpolarization. Changes in the level of [K]c induced by pre-pulses must therefore also affect the Erev determination. 4. A simplified three-compartment model has been used to investigate how K accumulation and depletion can affect the time course of iK2, with particular reference to the problem of Erev determination. Computed examples show that the model is able to reproduce the main features of the time course of iK2 recorded near its reversal potential and the changes induced by pre-pulses on Erev measuremnet. By contrast, simulation on a linear cable model rules out the possibility that such results are due to voltage non-uniformity. 5. The three-compartment model predicts that the measured value of Erev differs from EK2 for two reasons: (1) when the recorded current trace is flat iK2 is still outward and decaying, and (2) the K equilibrium potential shifts to more negative values while the test hyperpolarization is applied. 6. The finding that Erev is directly affected by changes in s at the beginning of the test pulse is discussed in relation to the action of agents (such as Ca2+, H+, salicylate, adrenaline and ouabain) which are found to shift both the s00 curve and Erev.


Action of salicylate ions on the electrical properties of sheep cardiac Purkinje fibres. 1. In sheep Purkinje fibre preparations, salicylate ions produce reversible changes in resting potential and in action potential duration. In most preparations these effects resemble those produced by -ow extracellular K concentration: the resting potential first increases and then decreases, the action potential is prolonged and eventually, low potential oscillations occur in the plateau range. In a few preparations, action potential shortening occurs. 2. The threshold current for initiating action potentials by an intracellular electrode is reversibly increased by salicylate. 3. The activation curve, soo(Em), for the pace-maker K current, iK2, shifted in a hyperpolarizing direction. The magnitude of the shift is about -5 mV in 5 mM-salicylate and -30 mV in 50 mM-salicylate. 4. The apparent reversal potential for iK2 is shifted in a negative direction. The magnitude of this shift at a given salicylate concent;ation varies with the K concentration. In an extracellular K concentration of 2.7 mM an average shift of -18 mV occurs in 10 mM-salicylate; in 8 mM, the average shift is only -1 mV. 5. It is proposed that most of these effects may be produced by an increase in surface negative potential produced by the binding of salicylate to the cell membrane. This would produce the hyperpolarizing shift of activation curves for ionic current and, by increasing surface K activity, may lead to stimulation of the Na-K pump to produce an increase in the K gradient across the cell membrane.


The interaction of ouabain and salicylate on sheep cardiac muscle. 1. The action potential duration in sheep ventricular fibres is rapidly diminished on exposure to 10(-6) M-ouabain. However, if 10--20 mM-sodium salicylate is added to the ouabain solution, glycoside-induced shortening is prevented, and a substantial increase in duration then occurs. Sodium salicylate also reverses the shortening effect of ouabain if applied after the glycoside has been allowed to act alone. 2. Sodium salicylate alone produces a much smaller prolongation than in the presence of ouabain. Alone and in the presence of ouabain it eventually increases the threshold and produces inexcitability. 3. Three other surface charge agents have been compared with salicylate: aminonaphthalene sulphonate, sodium dodecylsulphate and salicylamide, were unable to counter the actions of ouabain at the concentrations used. Since they also produced no changes in excitability it is likely that they did not bind significantly to the cell membrane. 4. In Purkinje fibres the reversal potential for the pacemaker current, iK2, is initially shifted in a negative direction in the presence of 10(-6) M-ouabain and 10 mM-salicylate instead of the positive shift expected with ouabain alone at this concentration. 5. In guinea-pig ventricle, salicylate alone reduces the duration of the action potential. This effect is rapidly reversible. Toxic levels of ouabain also reduce the action potential duration but this effect takes several hours to reverse. By contrast, the effects of salicylate and ouabain applied together are readily reversible. 6. It is suggested that the mechanism of these effects may depend on the ability of a surface negative charge agent like salicylate to increase the surface K+ concentration at the membrane and so protect the sodium-potassium pump from inhibition by large doses of ouabain.


The spread of sensitization of polymodal nociceptors in the rabbit from nearby injury and by antidromic nerve stimulation. 1. Ninety-three polymodal nociceptor units with unmyelinated axons were isolated from rabbit sural nerves. Twenty-three were used for control data. These showed normal sensitization on repeated heating of their receptive fields, measured here as a drop in mean heat threshold. 2. Small injuries were made 5 (n = 15) or 10 (n = 12) mm outside the receptive fields of some polymodal nociceptors. This resulted in the development of spontaneous firing and lowered thresholds to heating of the receptive field. 3. Local anaesthetic previously injected into the site of injury blocked this spread of heat sensitization. Previous injection of saline had no effect. 4. Antidromic stimulation of the sural nerve, proximal to the recording site, also resulted in heat sensitization of polymodal nociceptors (n = 10). 5. Possible mechanisms for the spread of sensitization of polymodal nociceptors from nearby injury are discussed. Analogies are drawn between these results and those of Lewis (1935--36) on the spread of cutaneous ;yperalgesia around a skin injury in man.


Changes in recurrent inhibition during voluntary soleus contractions in man studied by an H-reflex technique. 1. The recurrent inhibition, brought about by a conditioning H-reflex discharge, was estimated in human subjects by the amplitude of a test H-reflex involving only the soleus motoneurones which fired in response to the conditioning volley. The modifications of the recurrent inhibition during contraction were evaluated by comparing the amplitude of the test H-reflex to a reference H-reflex. Both reflexes experienced the excitation underlying the voluntary contraction, but only the test H-reflex was subjected to the recurrent inhibition evoked by the conditioning H-reflex discharge. 2. Distinct differences were observed between the modifications of the test reflex and those of the reference H-reflex during both tonic and phasic voluntary contractions. Evidence is presented that these differences were due to changes in the amount of recurrent inhibition elicited by the conditioning discharge. 3. The changes in recurrent inhibition were studied while the subjects performed voluntary tonic contractions of various forces. The weakest contractions were accompanied by a decrease in the size of the test reflex. With greater contraction forces, there was no longer an inhibition of the test reflex, but instead a facilitation which grew continuously with increased contraction forces. The test reflex could eventually exceed the reference H-reflex amplitude at the strongest contractions. This is taken to indicate that the recurrent inhibition following the conditioning discharge was progressively decreasing, as the contraction force increased. 4. During ramp contractions, whatever the contraction velocity, the time courses of the variations of the test and reference H reflexes were almost inverse. Evidence is presented that these differential time courses were due to changes in the amount of recurrent inhibition elicited by the conditioning discharge. 5. The possibility of occlusion in the recurrent pathway ;as considered and it was concluded that the decrease in the recurrent inhibition elicited by the conditioning discharge was essentially due to an inhibitory control (spinal and/or suprasegmental) acting on Renshaw cells. This inhibition of Renshaw cells eventually counteracts the increasing excitatory inputs (resulting from the voluntary motor discharge) which they receive via motor axon collaterals during increasing tonic contractions and throughout ramp contractions. 6. The functional significance of the Renshaw cell inhibition during voluntary contraction is discussed in relation to the inhibition exerted through the recurrent pathway on both motoneurones and Ia inhibitory interneurones. It is suggested that the depression of Renshaw cell activity could play an important role during voluntary movements by favouring reciprocal Ia inhibition.


Recurrent inhibition and afterhyperpolarization following motoneuronal discharge in the cat. 1. The relation between the size of a monosynaptic reflex (varying from the smallest values to the maximal motor response) and the output from Renshaw cells was investigated. This relation was extremely variable from one Renshaw cell to another. However, a linear relation between the reflex size and the early discharge emerged when the responses of all the Renshaw cells were averaged or when the summed activity of a pool of Renshaw cells was estimated by recording the recurrent inhibition in their target motoneurones. It was concluded that the lowest threshold motoneurones were efficient in producing recurrent inhibition. 2. In motoneurones, recorded intracellularly, the size of the depression caused by the afterhyperpolarization was compared to the maximum autogenetic recurrent inhibition. Under the particular experimental conditions used to mimic human experiments (Hultborn & Pierrot-Deseilligny, 1979a), it was found that recurrent inhibition had the same order of magnitude as the depression caused by afterhyperpolarization. 3. The additional depression caused by the summation of afterhyperpolarizations of two consecutive spikes was measured. It was shown that a summation of importance equal to the maximum autogenic recurrent inhibition required a mean interspike interval of 25 msec.


A method for investigating the role of calcium in the shape change, aggregation and serotonin release of rat platelets. 1. Effects of the platelet secretagogues thrombin and Concanavalin A (Con A) on shape change and release have been studied under conditions where external Ca2+ and ADP have been controlled. 2. In the absence of detectable aggregation both Con A- and thrombin-induced release of serotonin are markedly dependent upon extracellular calcium. 3. Con A, unlike thrombin, does not produce aggregation in calcium-supplemented medium. 4. The above property of Con A suggests that, in combination with added creatine phosphate and creatine phosphokinase, this ligand will be of value in the analysis of calcium-dependent release in platelets.


Estimates of cable parameters in lamprey spinal cord neurones. 1. Two micro-electrodes were used to penetrate giant interneurones in the isolated lamprey spinal cord. A brief (50--100 microsec) current pulse was applied to one electrode while the other recorded the voltage transient response. 2. A formal analysis of the voltage transient was achieved by the simplifying reduction of each neurone. Somas were treated as a parallel combination of resistance and capacitance. Dendrite trees were reduced to an equivalent cylinder (Rall, 1959). 3. The voltage transients were analysed according to the procedure suggested by Jack & Redman (1971b) to estimate the cable parameters governing the passive propagation of transmembrane potentials. Membrane time constant (tau m), dendritic to soma conductance ratio (rho 00), and electrotonic length (L) of the equivalent cylinder were estimated from these data. 4. In thirty-two interneurones it was possible to determine the membrane time constant, but rho 00 and L were determined in only twenty-two. 5. For the twenty-two neurones in which all cable parameters were estimated, the electrotonic length of the equivalent cylinder was similar to that found for cat spinal motoneurones (1--2 space constants). 6. Simulations of the voltage transient using the Rall model of the motoneurone as developed by Jack & Redman (1971b) resulted in a voltage response which closely ditted the experimental data. 7. These results suggest that the Rall model of the motoneurone accurately describes the propagation of passive transmembrane potentials in lamprey spinal cord neurones. It is further concluded that the time constant for soma and dendritic membrane is similar in these neurones.


Localization of synaptic input on dendrites of a lamprey spinal cord neurone from physiological measurements of membrane properties. 1. Composite excitatory post-synaptic potentials (e.p.s.p.s) resulting from electrotonic and chemical synaptic junctions were recorded from eighteen interneurones following stimulation of the I2 burster axon in the isolated lamprey spinal cord. 2. In each cell, the half-width of the electrotonic e.p.s.p. was measured and used, together with the cable parameters estimated for the same neurone, to locate the position of synaptic contact made by the I2 axon on the dendrites of the interneurone. The synaptic location ranged from 0.05 to 1.35 space constants with a mean of 0.46. 3. The synaptic potential was simulated using the Rall model of the neurone. When compared with the experimentally recorded e.p.s.p. with the same half-width, the rise-time of the simulated synaptic potential was found to be faster. By changing the value of synaptic distance and/or synaptic current duration the half-width, rise-time, and decay of the simulated synaptic potential fit closely the experimental e.p.s.p. The range of synaptic distance estimated from the simulation decreased considerably (0.2--0.7 space constants; mean 0.52). 4. Direct comparison of synaptic location estimated from histological tracings of dendritic trees from these same cells injected with horseradish peroxidase compared favourably with synaptic location estimated from the simulations. 5. These results support the hypothesis that functionally similar presynaptic axons make synaptic connexions at the same electrotonic distance from the soma on functionally similar post-synaptic cells. This occurs in the face of large variations in physical distance for these same synaptic contacts.


Anion exchange and volume regulation during metabolic blockade of renal cortical slices. 1. The development of swelling of rat and guinea-pig renal cortical slices was studied after metabolic blockade (hypoxia plus glycolytic blockade with iodo-acetic acid) and/or exposure to 'isotonic' high potassium, no sodium solution. 2. Swelling was greater after exposure to oxygenated high potassium solution than after metabolic blockade in physiologic Krebs-Henseleit solution. Swelling was reduced after metabolic blockade in high potassium solution compared to incubation in oxygenated high potassium solution. Increasing periods of transient metabolic blockade in Krebs-Henseleit solution progressively blunted swelling when slices were subsequently incubated in oxygenated high potassium solution. 3. Metabolic blockade in Krebs-Henseleit solution resulted in marked reductions in potassium and increases in sodium. Incubation in high potassium solution resulted in marked increases in potassium and similar low levels of sodium regardless of associated interventions. Metabolic blockade in both media resulted in significantly greater increases in renal cortical chloride than in monovalent cations (potassium plus sodium). Incubation in oxygenated high potassium solution was associated with similar increases in renal cortical chloride and total monovalent cations. 4. Renal cortical losses of solids and protein and increases in renal cortical inulin space were greater after metabolic blockade than after incubation under oxygenated conditions regardless of the incubation media. 5. These data support the conclusion that during metabolic blockade there is a significant replacement of larger intracellular anions by extracellular chloride. The loss of osmotically active intracellular anions limits the increase in renal cortical volume during metabolic inhibition and exposure to high potassium solution.


Detection of tactile stimuli. Thresholds of afferent units related to psychophysical thresholds in the human hand. 1. Psychophysical thresholds were determined at 162 points in the glabrous skin area of the human hand when slowly rising, triangular indentations of controlled amplitudes were delivered with a small probe. The method of constant stimuli was used with either the two alternative forced choice or the yes-no procedure. It was found that the distribution of the psychophysical thresholds varied with the skin region. Thresholds from the volar aspect of the fingers and the peripheral parts of the palm were low and their distribution was unimodal with a median of 11.2 micrometers. In contrast, there was an over-representation of high thresholds when observations from the centre of the palm, the lateral aspects of the fingers and the regions of the creases were pooled, and the distribution was slightly bimodal with a median of 36.0 micrometers. 2. Nerve impulses were recorded from single fibres in the median nerve of human subjects with percutaneously inserted tungsten needle electrodes. The thresholds of 128 mechanosensitive afferent units in the glabrous skin area of the hand were determined when stimuli were delivered to partly the same points as stimulated for the assessment of the psychophysical thresholds. Of the four types of units present in this area the Pacinian corpuscle (PC) and rapidly adapting (RA) units had the lowest thresholds with medians of 9.2 and 13.8 micrometers, followed by the slowly adapting type I and slowly adapting type II units with medians of 56.5 and 33.1 micrometers. There was no indication of a difference between thresholds of units located in different skin areas. 3. In the region of low psychophysical thresholds there was good agreement between the thresholds of the rapidly adapting and Pacinian corpuscle units and the psychophysical thresholds, particularly at the lower ends of the samples. In the skin regions of high thresholds, on the other hand, practically all psychophysical thresholds were higher than the thresholds of the most sensitive afferent units. Moreover, simultaneous recording of nerve impulses during a detection task indicated that subjects did not detect stimuli strong enough to elicit several impulses in afferent units in this region. 4. Circumstantial evidence led to the conclusion that detection was dependent on one impulse in one or a few rapidly adapting units under optimal conditons in the region of low psychophysical thresholds, whereas it seemed unlikely that activity in Pacinian corpuscle units was crucial. 5. The findings are consistent with the interpretation that human subjects are able to detect an input consisting of a single impulse in a single rapidly adapting unit.


Ionic mechanisms of repolarization in the guinea-pig taenia coli as revealed by the actions of strontium. 1. The actions of Sr2+ on the smooth muscle of the guinea-pig taenia coli have been studied under constant-current and voltage-clamp conditions. 2. In replacing Ca2+, Sr2+ (2.5 mM) prolongs the duration of the action potential by slowing the rate of repolarization, but increases the steady-state membrane conductance. These changes occur in preparations in Krebs solution as well as in preparations in a Na+-free tetraethylammonium medium. 3. When [Sr2+]o is increased to 20 mM, the amplitude of the spike is increased, and the duration shortened. 4. Under voltage-clamp conditions, Sr2+ carries the early inward current (Ia). Increasing [Sr2+]o increases the maximum Ia and shifts its reversal potential (Ea) towards more positive voltages, without affecting the conductance, ga. 5. Sr2+ does not affect the steady-state inactivation of Ia, but markedly slows the rate of inactivation. 6. In all concentrations, Sr2+ enhances the late outward current (Ib, chiefly Ik), by increasing the conductance, gb. The degree of increase is greater in higher [Sr2+]o. 7. Ca2+ at concentrations of 1 or 2.5 mM added to Sr2+ solutions partially reverses the above effects, suggesting the presence of some competition for the same channel or binding sites or both. 8. The results indicate that in the taenia coli, there is a component of the K+-conductance system which is sensitive to [Sr2+]o and to [Ca2+]o. 9. They also suggest that the inactivation of the early inward current is an important mechanism underlying the repolarization of the action potential, and that IK probably has a delayed and gradual onset.


The size of motor units during post-natal development of rat lumbrical muscle. 1. The number of muscle fibres innervated by individual motor neurones (motor unit size) was measured in lumbrical muscles of rats aged 0--28 days, during the period of elimination of polyneuronal innervation. Motor unit sizes were determined from twitch tension measurements combined with muscle fibre counts made from histological sections of the muscles. 2. The relative tensions contributed by individual motor units declined from about 25% of the total tension at birth, to about 9% at 28 days of age. Intracellular recordings showed that part of this decrease reflected the elimination of synapses from polyneuronally innervated muscle fibres. 3. During the same period, however, new muscle fibres were produced. The total number of muscle fibres present increased from about 500 at birth to about 950 fibres in mature muscles. 4. These two processes were offsetting: some synapses were eliminated (from polyneuronally innervated fibres) while simultaneously others were formed de novo (on newly produced muscle fibres). Quantitative measurements showed that for the first 10 days after birth, there was little change in motor unit size. Thereafter production of new muscle fibres ceased, and motor unit size decreased to the adult level. 5. It is concluded that during early post-natal development, a lumbrical motor neurone maintains a nearly constant number of synapses, but extensively reorganizes its synaptic field, retracting synapses from some muscle fibres, while forming new synapses with other fibres.


Thyroid hormones and the energetics of active sodium-potassium transport in mammalian skeletal muscles. 1. The steady-state heat production rate (E) of soleus muscles obtained from adult mice in various thyroid states was measured in a perfused microcalorimeter. The ouabain-suppressible fractions of E and 42K influx were compared and the energetic efficiency of active Na-K transport assessed. 2. Hypothyroidism with plasma thyroxine concentrations below 1 microgram/100 ml. was induced by pretreatment with 131I or perchlorate. In soleus muscles isolated from treated animals, mean E values were 25.1 +/- 0.7 and 24.2 +/- 0.5 mcal.g wet wt.-1.min-1 for the 131I and the perchlorate series respectively, i.e. about 30% lower than the control level (36.3 +/- 1.5 mcal.g wet wt.-1.min-1). Following triiodothyronine treatment, E was increased by about 45%. 3. In muscles from hypothyroid (131I and perchlorate series), euthyroid and hyperthyroid mice ouabain (10(-3) M) induced a rapid decrease in E of 1.6 +/- 0.1 and 1.4 +/- 0.1, 2.5 +/- 0.2, and 4.3 +/- 0.6 mcal.g wet wt.-1.min-1 respectively, i.e. between 6 and 8% of E. 4. In muscles obtained from hypothyroid, euthyroid and hyperthyroid mice, the ouabain-suppressible component of 42K influx was 0.17 +/- 0.04, 0.31 +/- 0.02 and 0.45 +/- 0.02 micromole. g wet wt.-1.min-1 respectively. Whereas the total number of ouabain binding sites varied appreciably with the thyroid status, the Na-K contents of soleus or diaphragm muscles showed no significant changes. 5. Notwithstanding the parallelism between the changes in basal E and ouabain-sensitive components of E and K influx with the thyroid status, it is concluded that active NA-K transport cannot be considered a primary effector of thyroid thermogenesis in intact mammalian skeletal muscle. The direct contribution of active NA-K transport to this thermogenesis was indeed small compared with the over-all cellular energy dissipation. 6. The minimum over-all energetic efficiency of the transport process in the intact muscles (30--35%) was not dependent on the thyroid status.


The effects of renal denervation and meclofenamate on renal blood flow regulation in conscious rabbits. 1. The effect on renal blood flow regulation of unilateral renal denervation followed by administration of a prostaglandin synthesis inhibitor has been studied in nine conscious rabbits.2. Renal blood flow distribution was estimated using radioactive microspheres injected via a pre-implanted left ventricular cannula. Cardiac output was estimated by thermodilution. Measurements were made before and after intravenous injection of Meclofenamate, Parke Davis Ltd (4 mg/kg).3. Renal denervation caused a fall in renal cortical catecholamine concentration of approximately 50% by 48 hr.4. Resting renal blood flow did not differ significantly between denervated and innervated kidneys.5. Meclofenamate caused a significant rise in arterial pressure from a mean of 59 to 70 mmHg. In innervated kidneys, Meclofenamate caused a fall in renal blood flow from 8.1 +/- 0.6 (mean +/- S.E. of mean) to 6.5 +/- 0.4 ml./min.g kidney weight while in denervated kidneys it caused a fall from 8.9 +/- 0.7 to 6.25 +/- 0.3 ml./min.g. After Meclofenamate flow was redistributed away from the inner cortex in the innervated kidney and paradoxically towards the inner cortex in the denervated one.6. It was concluded that in conscious animals, resting sympathetic tone has little effect on renal blood flow. The exaggerated reduction in flow in the outer cortex of the denervated kidney following Meclofenamate may indicate denervation hypersensitivity to circulating catecholamines unmasked by reduced synthesis of vasodilator prostaglandins. Alternatively, renal sympathetic nerves may normally prime prostaglandin synthesis in the outer cortex.


Voltage clamp analysis of acetylcholine receptor desensitization in isolated mollusc neurones. 1. Desensitization produced by acetylcholine (ACh) in completely isolated Limnaea stagnalis neurones with chloride-selective membrane channels was studied using a voltage-clamp technique. 2. A difference in the time course of the neurone responses to ACh, depending on whether the measured parameter was voltage or current, was observed and explained on the basis of an equivalent electric scheme of the neurone soma membrane. 3. Desensitization onset was shown not to depend on membrane potential in the range of -30 to -120 mV. 4. Variation of external Ca2+, Na+ and Cl- concentrations over a wide range had little influence on the onset of desensitization and recovery from it. 5. An obvious difference is shown to exist between features of desensitization in mollusc neurone and frog muscle end-plate ACh receptors.


Arterial pressure and pulse interval responses to repetitive carotid baroreceptor stimuli in man. 1. Carotid baroreceptors of eight healthy young men were stimulated with brief (0.6 sec), moderate (30 mmHg), single or repetitive (2, 3 or 5), R wave coupled neck suction during held expiration, and brachial arterial pressure and pulse interval changes were measured for 10 sec. 2. Mean systolic arterial pressure declined significantly from control levels after single or multiple baroreceptor stimuli. The reduction of systolic pressure was significant within the first sec after the onset of trains of baroreceptor stimuli; its duration was proportional to the number of stimuli. 3. The sinus node response to a single baroreceptor stimulus was biphasic: inhibition was followed by less intense, but more prolonged facilitation (cardio-acceleration). A single baroreflex stimulus modulated sinus node function for about 7 sec. The integral of sinus node inhibition was linearly related to the number of baroreceptor stimuli. Inhibition with five repetitive stimuli peaked at about 1.5 sec after the onset of stimulation and delcined to a new steady-state level during the period of baroreceptor stimulation. 4. Human baroreflex adjustments of arterial pressure and sinus node function occur very early after a step increase of phasic baroreceptor afferent activity. The perturbation of sinus node function is complex and probably reflects changing temporal relationships between the arterial pulse and sinus node activity, and interactions between oscillating levels of acetylcholine and sinus node responsiveness to acetylcholine.


Selective antagonism of amino acid-induced and synaptic excitation in the cat spinal cord. 1. The effects of D-alpha-aminoadipate (DalphaAA), D-alpha-aminosuberate (DalphaAS) and other excitatory amino acid antagonists have been compared on the excitatory responses of neurones of the cat spinal cord to acetylcholine, a range of glutamate-related amino acids and stimulation of appropriate excitatory synaptic pathways. The ionophoretic technique was used for administration of excitants and antagonists. 2. DalphaAA and DalphaAS had little or no effect on acetylcholine-induced excitation of Renshaw cells. Responses of either Renshaw cells or dorsal horn neurones in the spinal cord to excitatory amino acids were depressed in the order: N-methyl-D-aspartate (NMDA), L-homocysteate, D-glutamate, ibotenate greater than D-homocysteate, L-aspartate, D-aspartate greater than L-glutamate, kainate and quisqualate. 3. These effects are consistent with the existence of different excitatory amino acid receptors, one type being sensitive to the actions of the antagonists, and activated predominantly by the NMDA group of excitants, with other receptors being relatively insensitive to DalphaAA and DalphaAS and activated predominantly by quisqualate and kainate. On this hypothesis, many amino acids are assumed to have mixed actions on DalphaAA-sensitive and -insensitive receptors. 4. 2-Amino-4-phosphonobutyrate (2APB) and L-glutamic acid diethyl ester (GDEE) produced different patterns of antagonism of excitatory amino acid-induced responses from those observed with DalphaAA and DalphaAS. Neither substance was as potent as DalphaAA or DalphaAS as an excitatory amino acid antagonist. 5. Both DalphaAA and DalphaAS selectively antagonized synaptic excitation of Renshaw cells evoked by dorsal root stimulation without affecting cholinergic excitation of these cells evoked by ventral root stimulation. These latter responses were selectively antagonized by dihydro-beta-erythroidine (DHbetaE). DalphaAA also antagonized synaptic excitation of unidentified dorsal horn neurones of the spinal cord evoked by dorsal root stimulation. Neither GDEE (particularly) nor 2APB were as effective as DalphaAA or DalphaAS as depressants of synaptic excitation. 6. Taken in conjunction with the results of in vitro studies on the specificity of action of Dalpha¿ and related substances, these observations suggest that certain synaptic excitations in the spinal cord are mediated by an excitatory amino acid transmitter, and that this transmitter interacts with receptors which are activated selectively by NMDA, less selectively by other amino acids, including L-aspartate, and probably only slightly by quisqualate, kainate and (exogenous) L-glutamate.


Sodium-sodium exchange through the sodium pump: the roles of ATP and ADP. 1. We have developed a procedure for preparing resealed red cell ghosts that contain ADP but very little ATP. 2. The procedure involves (i) lysis of the cells in a very large volume of lysing solution, (ii) resuspension of the ghosts in a small volume, (iii) the incorporation into the ghosts, before they are resealed, of the adenylate kinase inhibitor P1,P5-di(adenosine-5'-)pentaphosphate (AP5A) and of hexokinase, and (iv) the removal of traces of ATP, formed by residual adenylate kinase activity, by the addition of glucose. 3. Measurements of sodium efflux from ghosts prepared in this way show that sodium-sodium exchange through the sodium pump does not occur in the absence of ATP even if ADP is present. 4. The beta:gamma imido analogue of ATP (AMP.PNP), which is incapable of phosphorylating sodium, potassium-ATPase, cannot replace ATP in supporting sodium-sodium exchange. 5. These findings support the hypothesis that the outward movement of sodium ions through the sodium pump is associated with the transfer of a phosphoryl group from ATP to the enzyme, and that the inward movement of sodium ions through the pump is associated with the return of a phosphoryl group from the phosphoenzyme to ADP.


Interaction of permeant ions with channels activated by acetylcholine in Aplysia neurones. 1. Aplysia neurones with an excitatory response to acetylcholine (ACh) were voltage-clamped, and the ACh-induced currents were studied using noise and relaxation techniques. The mean channel open time, tau, and the amplitude of the elementary current, iel, were determined from these experiments, and the variation of these parameters with the ionic content of the extracellular solution was analysed. The goal of this work was to test whether permeant ions may bind in a voltage-dependent manner to channel sites and thereby hinder channel closing, as has been proposed before (Ascher, Marty & Neild, 1978a). 2. The relation between tau and the membrane potential V has a similar shape in normal sea water and after total replacement of Na ions with Li or Cs. In contrast, the shape of the tau(V) relation is modified if Na is replaced by Mg, Sr, or Ba. 3. Replacing the divalent cations (Mg and Ca) present in normal sea water with Na results in a decrease of tau and an increase of iel. Both effects are enhanced by cell hyperpolarization. 4. Similarly partial replacement of Na by Sr causes a voltage-dependent decrease of iel. 5. Experiments were performed in solutions containing Na and sucrose, or Mg and mannitol. In both cases tau was smaller than in an isotonic Na or Mg solution. 6. None of the above observations can be accounted for on the sole basis of outer surface potential changes. 7. A quantitative model of the interaction between permeant ions and ACh-sensitive channels is proposed. The possible relevance of this model for the interpretation of tau(V) curves in other systems is discussed.


The effects of post-ganglionic axotomy on selective synaptic connexions in the superior cervical ganglion of the guinea-pig. Stimulation of preganglionic axons arising from different levels of the thoracic spinal cord causes different effects on end-organs supplied by the superior cervical ganglion (Langley, 1892; Nja & Purves, 1977a; Lichtman, Purves & Yip, 1979). For example, stimulation of the first thoracic ventral root (T1) causes pupillary dilatation and widening of the palpebral fissure; stimulation of T4, on the other hand, has little effect on the eye, even though axons arising from this level innervate about as many superior cervical ganglion cells as those from T1. Thus ganglion cell innervation is selective. (1) Three months after crushing the major post-ganglionic branches of the superior cervical ganglion this differential effectiveness is lost: T1 and T4 stimulation have approximately equal effects on the end-organs of the eye. (2) In normal animals, the cellular counterpart of selective end-organ effects is the innervation of each ganglion cell by a contiguous subset of the spinal segments that innervate the ganglion as a whole. One of these segments is usually dominant, the strength of innervation from adjacent segments falling off as a function of distance from the dominant one (Nja & Purves, 1977a). Intracellular recordings from ganglion cells 3 months after post-ganglionic axotomy showed that this selective pattern is re-established. (3) Since the innervation of ganglion cells appears normal, the abnormal end-organ responses after post-ganglionic axotomy suggest that ganglion cell axons are not limited to their original targets during peripheral re-innervation. This suggestion is supported by the finding that ganglion cells sending axons to different peripheral destinations via the second and third cervical spinal nerves were no longer distinguishable on the basis of their segmented inputs 3 months after post-ganglionic axotomy. (4) Similar results were obtained when the preganglionic cervical trunk was cut at the same time as the post-ganglionic axons were crushed; the pattern of end-organ responses was abnormal, whereas individual ganglion cells were re-innervated according to the rules of contiguity and segmental dominance. (5) These results indicate that ganglion cells do not undergo a compensatory change in the segmental innervation they receive when their axons regenerate to targets different from, or in addition to those they originally innervated, even when an entirely new set of ganglionic connexions is formed. This suggests that ganglion cells, or some aspect of their immediate environment, possess a permanent label that determines the segmental innervation they receive.


Ultrastructural study of schizogony of Eimeria bovis in cell cultures. First-generation schizogony of Eimeria bovis in bovine cell culture was studied by electron microscopy. The intracellular sporozoite retained its structure for at least 6 days at which time it rounded up and lost its apical complex. Although the refractile body underwent certain morphologic changes, it was retained throughout the parasite's growth. The beginning of mitosis was marked by the formation of a cytoplasmic funnel which traversed the nucleus opening on each side toward a pair of centrioles. Subsequently, there developed an intranuclear spindle. Separation of the daughter nuclei was preceded by the formation of typical centrocones. Differentiation of merozoites was accomplished by exogenesis during the last mitotoc division. A dense fiber, interpreted as a link connecting the merozoite anlage with its nucleus, extended from the developing apical complex to the nearest division pole. In the anlage, the inner membrane complex was at first composed of patches associated with pairs of subpellicular microtubules. Rhoptries appeared early in merogenesis, whereas micronemes formed at the time the merozoites detached from the residuum. The level of amylopectin, low in schizonts, rose at the beginning of merozoite formation.


Cyclical transmission of Trypanosoma brucei rhodesiense and Trypanosoma congolense by tsetse flies infected with culture-form procyclic trypanosomes. Culture procyclic forms of Trypanosoma brucei rhodesiense and Trypanosoma congolense were fed to Glossina morsitans morsitans through artificial membranes. A very high percentage of the flies so fed produced established midgut infections, a proportion of which went on to develop into mature metacyclic trypanosomes capable of infecting mammalian hosts. The method offers a safe, clean way of infecting tsetse flies with African trypanosomes which reduces the need for trypanosome-infected animals in the laboratory.


Infectivity of Trypanosoma brucei cultivated at 28 C with tsetse fly salivary glands. When transformed procyclic noninfective trypanosomes of several unrelated stocks of Trypanosoma brucei were cultivated in T-30 Falcon flasks at 28 C in a liquid medium containing head-salivary gland explants of Glossina morsitans morsitans some of the organisms developed into forms infective for mice. Infective trypanosomes were detected 7 to 14 days after the cultures were prepared and they persisted for varying periods of up to 88 days when the cultures were terminated. A few of the salivary glands became invaded with parasites about the time infective organisms appeared in the cultures. Using T. brucei TREU 929, it was shown that trypanosomes grown with between 2m and 50 explants were capable of producing infections consistently for prolonged periods. On the other hand, trypanosomes cultivated with 25 or fewer explants rarely infected mice. Infectivity titrations on trypanosome suspensions from cultures of stocks TREU 1275 and TREU 929 revealed that the maximum number of infective organisms was present 26 to 50 days after initiation of the cultures. Control cultures of trypanosomes grown in medium alone were generally not infective but 2 of the 6 stocks gave rise to a few sporadic infections. A few epimastigote-like and metacyclic-like trypanosomes were seen in stained preparations of infective inocula.


Life cycle of Isospora rivolta (Grassi, 1879) in cats and mice. The endogenous development of Isospora rivolta (Grassi) was studied in cats fed oocysts, and was compared with the endogenous cycle after feeding them mice infected with I. rivolta. For the mouse-induced cycle, 14 newborn cats were killed 12 to 240 h after having been fed mesenteric lymph nodes and spleens ofmice. Asexual and sexual development occurred throughout the small intestine, in epithelial cells of the villi and glands of Lieberkühn. The number of asexual generations was not determined with certainty, but there were at least 3 structurally different meronts. Type I meronts appeared at 12-48 h postinoculation (HPT). They were 8.5(6-13) x 5.1(3-6) micrometer, contained 2-8 merozoites, and divide by binary division or endodyogeny. Type II meronts were multinucleate merozoite-shaped meronts within a single parasitophorous vacuole. They were found at 48-172 HPI and measured 12.6(9-18) x 9.8(9-13) micrometer. Individual multinucleate merozoite-shaped meronts were 7-13 x 3-5 micrometer in sections and contained 2-30 slender (5.5 x 1.0 micrometer) merozoites. Type III meronts occurred at 72-192 HPI and gamonts at 72-96 HPI. Mature microgamonts measured 11.3(9-15) x 8.0(6-9) micrometer in sections and up to 21.5 x 14 micrometer in smears, and contained up to 70 microgametes. Macrogamonts measured 13.3(11-18) x 9.0(5-13) micrometer in sections and 18 x 16 micrometer in smears, and contained up to 70 microgametes. Macrogamonts measured 13.3(11-18) x 9.0(5-13) micrometer. Sporulation was completed within 24 h at 22-26 C. For the study of the oocyst-induced cycle in cats, 18 newborn cats were killed between 6 and 192 HPI. The endogenous development was essentially similar to the mouse-induced cycle, but merogony and gametogony occurred 12-48 h later than in the latter cycle. Isospora rivolta was pathogenic for newborn but not for weaned cats. Newborn cats fed 10(6) sporocysts or infected mice usually developed diarrhea 3-4 days after inoculation. Microscopically, desquamation of the tips of the villi and cryptitis were seen in the ilium and cecum in association with meronts and gamonts. For the study of the development of I. rivolta in mice, mice were killed from day 1 to 23 months after having been fed 10(5)-10(6) sporocysts, and their tissues were examined for the parasites microscopically, and by feeding to cats. The following conclusions were drawn. (A) Isospora rivolta most freqeuntly invaded the mesenteric lymph nodes ofmice and remained there for 23 months at least. Ii also invaded the spleen, liver, and skeletal muscles of mice. This species could not be passed from mouse to mouse. Sporozoites increased in size from approximately 6.8 x 4.9 micrometer on day 1 to approximately 13.4 x 6.9 micrometer on day 31 postinoculation. Division was not seen. Prepatent period was 4-7 days and patent periods ranged from 2 to several weeks.


Development, ultrastructure, and mode of transmission of Amblyospora sp. (Microspora) in the mosquito. Amblyospora sp. in Culex salinarius (Coquillett) is transovarially transmitted and has 2 developmental sequences, one in each host sex. In females, the entire life cycle is restricted to oenocytes which become greatly hypertrophied due to the multiplication of diplokaryotic cells during merogony and come to lie next to ovaries. Sporulation occurs only after a blood meal is taken and is shortly followed by infection of the oocytes and subsequent transmission to the next host generation. In the male host, infections spread from oenocytes to adipose tissue where diplokaryotic cells undergo a 2nd merogony. During this merogonic cycle, the number of diplokaryotic cells greatly increases and the infection is spread throughout the body of the larval host. Sporulation is initiated with the physical separation of the 2 members of the diplokaryon and the simultaneous secretion of a pansporoblastic membrane. Subsequent meiotic division and morphogenesis result in the formation of 8 haploid spores enclosed with a pansporoblastic membrane. Buildup of spores and subsequent destruction of host adipose tissue prove fatal to the male host during the 4th larval stage.


Growth of Leishmania donovani amastigotes in a continuous macrophage-like cell culture. The feastibility of using a macrophage-like murine tumor cell as a host for Leishmania donovani was investigated. This cell line, designated P388D1, rapidly phagocytized amastigotes and supported their intracellular replication. It can serve as a model "host" without the inherent limitations of primary macrophage cultures.


Axenic Paramecium caudatum. I. Mass culture and structure. To establish and grow Paramecium caudatum in mass axenic culture the culture medium of Soldo, Godoy & van Wagtendonk was modified by substituting phosphatidylethanolamine (PE) for TEM-4T and by a 10-fold increase in folic acid. Population densities of 4000 to 6000 cells/ml and a generation time of 20-26 h are regularly obtained. Optimal growth is obtained with PE-stigmasterol ratios between 40:1 to 400:1. Cells from 1-day-old axenic cultures have many lipid bodies aggregated in clumps (which disappear in 2 to 3 days) as well as foci of rough endoplasmic reticulum bordered by dictyosomes. The latter suggests a very active metabolism. Crystalline sheets found in both food vacuoles and lysosomes presumably play a role in digestion. Axenically grown cells also have abundant Golgi bodies (dictyosomes) and by late log phase become filled with lysosomes.


Structure of the D-mannan and D-arabino-D-galactan in Crithidia fasciculata: changes in proportion with age of culture. Cells of the insect flagellate Crithidia fasciculata contained mannan and arabinogalactan components, whose porportion varied with culture age, the former predominating during early stages, and the latter during the later stages of exponential growth and the deceleration phase. The mannan was a beta-D-(1 leads to 2)-linked D-mannopyranan. The arabinogalactan had a complex structure containing, in part, a beta-D-(1 leads to 3)-linked galactopyranose main-chain substituted in the 2 positions by single-unit D-arabinopyranose side-chains and with some unsubstituted units.


Synthesis and content of polyamines in bloodstream Trypanosma brucei. The sensitive dansyl procedure was used to detect putrescine and spermidine, but not spermine and cadaverine, in pleomorphic Trypanosoma brucei. The polyamines were synthesized in vitro from [3H]ornithine, [14C]arginine and [14C]methionine. Proline, agmatine, and citrulline, but not glutamine, glutamic or pyroglutamic acids, stimulated spermidine formation from [4C]methionine. Putrescine and sperimidine synthesis occurred rapidly from ornithine: putrescine synthesis peaked in 0.5 h, spermidine in 1 h. Trypanosoma brucei assimilated exogenous 14C-labeled putrescine, spermidine, and spermine; spermidine and spermine were taken up 5 times as rapidly as putrescine. Polyamine syntheses may therefore be a practical target for novel trypanocies.


Plasmodium lophurae: membrane proteins of erythrocyte-free plasmodia and malaria-infected red cells. Plasma membranes of normal duckling erythrocytes were prepared by blender homogenization and nitro-en decompression. Surface membrane vesicles of red cells infected with the avian malaria Plasmodium lophurae were produced by nitrogen decompression. Membranes of erythrocyte-free malaria parasites were removed from cytoplasmic constituents by Dounce homogenization. These membranes were collected by centrifugation in a sucrose step gradient and purified on a linear sucrose gradient. Red cell membranes had a buoyant density of 1.159 g/cm3, whereas plasmodial membranes banded at 2 densities: 1.110 g/cm3 and 1.158 g/cm3. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the isolated red cell membranes revealed 7 major protein bands with molecular weights (MW) ranging from 230, 000 to 22,000, and 3 glycoprotein bands with MW of 160,000, 88,000 and 37,000. Parasite membranes also had 7 major bands with MW ranging from 100,000 to 22,000. No glycoproteins were identifiable in these membranes. The proteins of the surface membranes from infected red cells had MW similar to those from normal red cells; however, there was some evidence of a reduction in the amount of the high MW polypeptides. The red cell membrane contained 79 nmoles sialic acid/mg membrane protein, whereas plasmodial membranes had 8 nmoles sialic acid/mg membrane protein. The sialic acid content of the surface membranes of infected red cells was significantly smaller than that of normal cells. Lactoperoxidase-glucose oxidase-catalyzed iodination of intact normal and malaria-infected erythrocytes labeled 7 surface components. Although no observable differences in iodinatable proteins were seen in these preparations, there was a striking reduction in the iodinatability of erythrocytic membranes obtained from P. lophurae-infected cells. Erythrocyte-free plasmodia bound very little radioactive iodine; the small amount of radioactivity was distributed among 3 major bands with MW of 42,000, 32,000 and 28,000. It is suggested that the alterations of the surface of the P. lophurae-infected erythrocyte do not occur by a wholesale insertion of plasmodial membrane proteins into the red cell plasma membrane, but rather that there are parasite-mediated modifications of existing membrane polypeptides.


[Computed tomography of the mediastinum: normal anatomy and non pathologic variations in the adult (author's transl)]. This work is based on the separate study of a triple material: axial gross body sections from cadavers (4); normal and conventional radiographs with or without opacification; in vivo scans (210). Authors have selectionned thriteen scans patterns according to several regional levels: supra-aortic scans (n08 1, 2, 3); scan through the horizontal part of aortic arch (n0 4B); the scan of the aorto-pulmonary window (n0 4B); supra-cardiac scans through intra and extra-pericardic parts of great vessels: vena cava, aorta and pulmonary artery (n08 5, 6, 7); heart and cardiac cavities scans (n08 8, 9, 10, 11); scan through the retro-crural space (n0 12). Knowing these regional scan patterns, makes it possible to the radiologist to manage a topographic approach quite adapted to the technical mode of direct scannography through the area of interest, already tested by some constructors. The non pathologic variations are numerous. Mediastinal lipomatosis, dilated and tortuous great vessels in the older and atheromatic individual, constitutional variations of the vessels topography. Limits found out during this work concern heart examination and hilum study; great strides are to be achieved in these fields because of the unceasing technical improvments.


[Value of computer tomography during investigation of sub-diaphragmatic adenopathies occurring during the course of lymphomas and pelvic cancers (author's transl)]. A series of 60 patients were examined by abdominopelvic computer tomography 48 hours after foot lymphography. The diagnosis  was Hodgkins's disease in 10 patients, lymphomas other than Hodgkin's in 20 cases, and 30 patients with pelvic carcinomas. The value of lymphography in lymphomas other than Hodgkin's is re-emphasized, and a good correlation exists between the results obtained and those observed with computer tomography, which is particularly useful for studying the upper lumbo-aortic regions. The group of Hodgkin's disease patients particularly demonstrates the limits of pelvic lymph node investigations with computer tomography, but supplies confirmation of the quality of examination of the lumbo-aortic chains. The group of patients with pelvic carcinomas is more heterogenous, and computer tomography is if greater value, mainly in cases with blocked lymphatics. Computer tomography examinations do not replace lymphography in the study of sub-diaphragmatic lymph node chains but are a useful complement as they demonstrate excluded or poorly opacified adenopathies. When lymphography is contra-indicated, computer tomography can supply valuable information, but the differential diagnosis of inguino-iliac chain lesions is difficult. Computer tomography is a logical procedure during pretreatment investigations whenever there is a doubt concerning possible lesions in the lumbo-aortic chains. It is the most valid guide for establishing details of a course of radiotherapy.


[Warren's operation for distal splenorenal anastomosis. A pre- and postoperative radiological study (author's transl)]. The results of radiological examinations of 19 patients before and after Warren's operation for distal splenorenal anastomosis are reported, and compared to those of clinical and hemodynamic investigations. Good clinical results were obtained in this series in that there were no cases of relapse with hemorrhage, severe manifestations of encephalopathy, and/or hepatic insufficiency. Death occurred in 3 out of the 19 patients.  Hemodynamic studies demonstrated a reduction in hepatic blood flow, persistence of a superior hepatic gradient after operation reduction in blood flow in the anastomosis after clamping of the splenic artery during operation, which demonstrates the importance of splenic artery blood flow in maintaining the permeability of the anastomosis, and persistence of high portal vein pressure during operation and after anastomosis. Radiological examination showed that the anastomosis was permeable in all the cases in this series. The hepatic portal circulation, as measured by the diameter of the portal vein and the amount of intrahepatic protal vascularization, was reduced after the operation. This diminution increased with time, as shown by studies carried out 6 months and 1 year after the operation in 3 patients. Portogastric separation was effective in only 6 cases. In the other cases, the hepatic collateral venous circulation persisted, appeared, or increased. The gastric varices were seen to be draining into the splenorenal anastomosis in 2 cases followed-up after the operation. It appears, therefore, that distal splenorenal anastomosis produces a progressive portocaval by-pass. Comparing these results with those obtained in three other series reported in the published literature (WARREN [12], MOSIMANN [8], and VANG [17], showed that they were close to those obtained by VANG, as far as reduction in intrahepatic portal circulation is concerned, but rather different from those of WARREN in respect to the efficacy of portogastric separation.


[Lymph node involvement of squamous cell carcinoma of the oesophagus. Contribution of thoracic radiograph (author's transl)]. The authors studied standard thoracic radiographs (PA and lateral) and esophageal X ray examination with barium in 116 patients with a squamous cell carcinoma of the esophagus. Diagnosis of lymph node involvement was done in 21 cases. Is was only probable in 33 other cases. In 43 cases, lymph node are located near the primary tumor but in 11 cases, they are located at a certain distance from the primary lesion. These X ray, simple findings, seem to be very important for the radiotherapeutic treatment planning.


[Colonic changes in perinephritis. Value of double contrast examinations (author's transl)]. The differential diagnosis of cancer and abscesses of the kidneys with perinephritic inflammatory masses is sometimes difficult. In these cases, radiological examination of the colon can be of great value by demonstrating the presence of inflammatory colonic perivisceritis. Double contrast examination can reveal the presence, not only of an inflammatory type of narrowing, but characteristic changes in the mucous folds of the transverse "in palisade" type with thickening extending throughout the circumference of the colon. These appearances are totally different from those observed in malignant colonic perivisceritis. The use of double contrast examination of the colon, in cases of renal masses and associated fever, can enable the choice to be made of an adequate route of approach (lumbotomy), of it demonstrates the characteristic appearances of inflammatory perivisceritis.


[Neuroradiological investigations in the Arnold-Chiari syndrome. Value of computer tomography and myelography with amipaque (author's transl)]. The use of computer tomography and myelography with amipaque is of considerable value for establishing the diagnosis of the Arnold-Chiari syndrome. The cerebral lesion (hydrocephalus) can be clearly demonstrated, together with a hernia of the amygdalae, IVth ventricle abnormalities and the size and contents of any myelomeningocele present.


[Differential diagnosis of the tetralogy of Fallot (author's transl)]. The differential diagnosis of the tetralogy of Fallot includes three main types of condition: 1) Malformations which differ from Fallot in their extent, such as interventricular communications of type IV and pulmonary atresia with an open septum. 2) Malposition of the large vessels with pulmonary stenosis (double opening in the right ventricle, complete or corrected transposition). 3) Malformations associating an intraventricular shunt and another type of pulmonary stenosis (double chambered ventricle, interventricular membranous and muscular communication, common atrioventricular canal, single ventricle). An analysis of the findings in angiographic images can provide precise differential diagnosis of these pseudo-Fallots.


The management of hypertension--a survey of opinions among general practitioners. In order to clarify current opinion on aspects of the management of hypertension, a postal questionnaire was sent to all 420 general practitioners in the Lothian Health Board Area. Three hundred and nine doctors (74 per cent) replied.A high proportion were willing to undertake the investigation and follow-up of most hypertensive patients in general practice but there were conflicting opinions on the use of Phase 4 and Phase 5 in the measurement of blood pressure, the number and type of investigations which were appropriate, the level of diastolic blood pressure at which treatment should begin, and the level to which the diastolic blood pressure should be reduced with treatment.


The management of hypertension--a study of records in general practice. We investigated the management of a group of 322 hypertensive patients by 71 general practitioners in the Lothian Health Board Area by a survey of the general practitioners' records. Eighty-five per cent of patients were diagnosed by the general practitioner and 57 per cent were cared for entirely by him. Two thirds of the patients were women. Hospital referral was more common in men and in patients with high initial blood pressures. One third of patients had only one blood pressure recorded before treatment. The result of treatment as measured by the latest diastolic blood pressure was similar for patients treated by the general practitioner and those referred to hospital, being 100 mm Hg or less in 77 per cent of patients.


Screening for hypertension: some practical problems. In 1967/68, a screening examination was carried out on 18,277 male London civil servants, of whom 488 were referred to their general practitioners with high blood pressure. After this referral, 23 per cent did not attend their doctor and among those who did, a relatively high frequency of anxiety was noted. In one third of the patients, the general practitioners were already aware of the presence of hypertension, but were not treating it. This reluctance to treat asymptomatic people continued with the management of referred and confirmed newly diagnosed hypertensive patients. The problems associated with mass screening examinations can be overcome by careful, expensive and time-consuming preparations. Where the purpose is to find and treat newly diagnosed hypertensive patients then screening by general practitioners is likely to be a more cost-effective approach.


The treatment of hypertension with propranolol and bendrofluazide. In 101 hypertensive patients, the effects of a combination of propranolol and bendrofluazide were compared with those of each drug alone. After an introductory period with a placebo, the patients received, in a double-blind randomized trial, propranolol 80 mg twice a day, bendrofluazide 2.5 mg twice a day, or both drugs together twice daily. The combination produced significantly greater reductions in lying, standing, and post-exercise systolic and diastolic blood pressure than either drug separately. Side-effects were minimal and the combination was well accepted by patients.


[Premenstrual mastodynia: objective signs (author's transl)]. Mammary congestion is mainly a painful syndrome, principally related to diffuse edema of the gland, the radiological signs of which are described in this report. Excellent validity can be obtained by a trained observer of these signs. In contrast, however, thermographic signs are of less value, probably due to the presence of a more or less abundant superficial edema. This interferes with thermal propagation towards the skin covering, and could be the cause of the superficial hypothermia which is recorded in one third of patients with definite clinical congestion. Hormonal disturbances are observed frequently enough in this syndrome for them to be considered responsible for a large proportion of the congestive and edemaotus phenomena. Observation of these signs enables a choice of therapy to be made, but this is not discussed in this report.


Behavioural science in general practice. Dr Peter Sowerby has written an important criticism of Michael Balint's work based on his understanding of Karl Popper's writings. I dispute Sowerby's interpretation of Popper and disagree with his conclusions, which I suggest would lead general practice into a retreat. I believe Balint made a major contribution to general practice and has helped us towards practising whole-person medicine.


Primary care in Norway.

Primary care in Norway. The organization of primary care in Norway is described and the shortage of general practitioners, particularly in remote areas, discussed. Improvement in working conditions is one approach to solving this problem. However, enhanced status for the general practitioner, achieved by improvements in his vocational training, is acknowledged as an important prerequisite for better recruitment to general practice.


[A case of pulmonary distomiasis (author's transl)]. Pulmonary distomiasis due to Paragonimus westermani was discovered in a young 21-year-old patient from Thailand following several bouts of hemoptysis. The authors review the published literature and outline the principal characteristics of this affection, emphasizing the radiological appearances and the possible value of bronchial arteriography.


The hard way out.

The hard way out. Much recent discussion and publicity has been directed towards the problem of international self-poisoning as a cry for help, or as a manipulative procedure where patients have ensured that the suicide attempt is discovered in time for counter measures. I describe the successful and carefully planned suicide of a 72-year-old patient with a particular attitude to euthanasia and with no evidence of a depressive illness.


[Urethroperineal fistula in the left lateroposition (author's transl)]. The authors describe a case of urethroperineal fistula in the lateropostion. It is a rare malformation, with a varied symptomatology, which requires radiological investigations for its morphological and topographical study. Surgical treatment varies as a function of the site and size of the fistula. Basing their comments on the studies by STEPHENS [12], the authors try to give an embryological explanation of this affection.


Self-audit of prescribing habits and clinical care in general practice. General practitioners' prescribing habits were studied using encounter forms during a period of three years. Analysis of the first year's forms revealed examples of inappropriate prescribing, so an audit was undertaken on the treatment of fungal skin infections and coughs and colds in children. Data collection was continued for a further year to measure any changes in prescribing. Analysis after audit showed that more appropriate prescribing had reduced the number of drugs prescribed as well as the number of repeat consultations needed before resolution of the problem. These findings suggest that the continuous use of encounter forms can accurately reveal the prescribing habits of general practitioners. Self-audit can then be performed on a continuing basis with little disruption of the general practitioner's normal routine.


Medical audit--a preliminary report from general practice. As three single-handed practitioners who work in the same health centre, we decided to review our work in clinical management and preventive medicine. We used data contained in a simple medical information system but, where necessary, referred to the original problem-orientated medical records. The results showed that we did not always reach standards which we considered satisfactory but we feel this type of review is worthwhile and could be applied in many general practices.