Structure determination of lipid bilayers. A method of determining the phases of X-ray reflections from oriented model membrane systems at low resolution is described. The method involves deconvolution and requires that d less than or equal to 2v where v is the width of the head group region within the bilayer and d is the thickness of the bilayer. The method can be used with a single set of X-ray data and applies to lipid bilayers which have a relatively constant density in the hydrocarbon region. Phases for the first five or six orders of phosphatidylethanolamine and lecithin are derived. A refined analysis based upon deconvolution but using information inherent in the Fourier profile is also described.


Water and hermal diffusivity in a lipid-water smectic phase. We report the first application of light scattering to measurement of the hydrodynamic relaxation of inhomogeneities in water concentration within a multilamellar, or smectic A, phospholipid water system (dipalmitoyl) phosphatidyl choline). Although the relaxation process in the multilamellar phase is different from the diffusion process in liquid phases, the relaxation rate can be described in terms of a diffusion coefficient. For diffusion parallel to the lamellae, diffusion coefficients ranging from 8 x 10(-7) to 2 x 10(-5) cm2/s were measured over a range of temperature and water concentrations. We describe a model that expresses the diffusion coefficient in terms of the chemical potential for water inside the multilamellar phase and the effective thickness of a "free water zone." The deduced thickness of this free water zone is in good agreement with estimates from X-ray diffraction results. The activation energy for the diffusion process is also deduced from the data, and is found to decrease monotonically with increasing water concentration. We also found the thermal diffusivity to be about 10(-3) cm2/s with only a weak temperature and water concentration dependence. The experimental technique is a new version of forced Rayleigh scattering. The method uses the phase information of the scattered light to improve the ability to detect weak signals. Experimental details are reported.


A molecular mechanism of the energetic coupling of a sequence of electron transfer reactions to endergonic reactions. A molecular mechanism of the energetic coupling of a sequence of electron transfer reactions to endergonic reactions is proposed and discussed from a physical point of view. The scheme represents a synthesis of concepts of electron transfer by tunneling and the conformational and chemiosmotic aspects of energy coupling processes. Its relation to existing experimental information and theoretical models is discussed, and further experimental tests are suggested.


Changes of intracellular Ca++ as measured by arsenazo III in relation to the K permeability of human erythrocyte ghosts. A Ca-sensitive dye, arsenazo III, has been incorporated into resealed human erythrocyte ghosts and calibrated to monitor continuously micromolar concentrations of intracellular ionized Ca ([Ca++]i). When the external concentration of Ca is much greater than [Ca++]i, [Ca++]i increases because of a net balance between Ca influx and efflux. Dynamic changes in [Ca++]i regulate K efflux, which in turn may influence the rate of Ca influx. A procedure for purifying arsenazo III is also described.


Internal cesium alters sodium inactivation in Myxicola. When Myxicola giant axons are internally dialyzed with Cs+ as the sole cation, the time-course of prepulse inactivation is selectively accelerated compared to its rate with K+ dialysis in the same axons. This decrease in tauph occurs without any change in the magnitude or time-course of INa during step depolarizations and results in tauph/taush ratios near unity over most of the potential range in Cs+ dialyzed axons.


Temperature effects on gating currents in the squid giant axon. The effects of temperature (3 degrees-26 degrees C) on the nonlinear components of the displacement current were measured in internally perfused, voltage clamped squid axons. Steps of potential were applied from a holding potential of -70mV (outside ground) to values from -130 to +70mV and either the current or its integral (charge) was recorded as a function of time. For that component of the charge movement not linearly related to voltage, the total charge moved in a few milliseconds (about 1,500 electronic charges/micron2) between saturation limits (e.g. -100mV to +50mV) showed an apparent increase of 13 +/- 5% for a 10 degrees C rise in temperature. Attempts to fit the falling phase of the gating current (or charge) with the sum of two exponentials showed temperature effects on both components but there was considerable scattering. At short times, records for current or charge made at 16 degrees C, expanded by a factor alpha, superimposed on those made at 6 degrees C for alpha about 1.6. For long times alpha was about 2.3.


[Optimal structure of the arterial network of skeletal muscles]. A criterion of the optimal structure of muscle arterial network consisting in the minimization of its hydraulic resistance is proposed. Application of this criterion allows one to determine the relationship between the mean values of diameters of vessels of different "orders of branching". Dependence of hydraulic resistance, volumes, blood-flow velocity and pressure in vessels of various calibres on the number of the "order of branching" was established. Rough quantitative estimates are given for the potential increase in the bloodflow of the working muscle as compared to the resting one.


[Effect of dehydration on the interstitial cells of the renal papilla]. There are two types of cells in the population of the interstitial cells of the albino rat renal papilla basement; these types differ by the development of endoplasmic reticulum. The cells with poorly developed reticulum prevail in the intact rats. The cells with highly developed reticulum characterise the renal tissue of dehydrated rats. It is suggested that the main function of the interstitial cells is connected with the activity of the granular endoplasmic reticulum.


[Deformation of the transpulmonary pressure plateau in experimental pulmonary emphysema]. Deformation of the transpulmonary pressure plateau occurring during the interruption of air flow for 0.5 s is described in 8 healthy rabbits and in 9 animals with experimental emphysema induced by the intravenous injection of licopodium spores. The greatest plateau deformity was seen in healthy animals during inspiration, averaging 20 cm H2O. In sick rabbits the degree of deformity was decreased by 13 cm H2O on the average. The plateau deformity was the same in expiration in healthy and sick animals, averaging 7 cm H2O. The direction of changes in the strain of respiratory muscles in response to inspiration or expiration during the air flow interruption was controlled by recording the pressure in the bronchus, whose amplitude of respiratory variations considerably exceeded such of transpulmonary pressure. Inspiratory plateau deformity is regarded to be the result of active sucking action of the lungs, and expiratory plateau deformity--as their active contraction under conditions of the air flow interruption.


[Electrical activity of motor unit action potentials following spinal cord injury]. The author studied the action potentials (AP) duration of the gastrocnemius and the tibial muscles motor units (MU) in patients with the spinal cord trauma by means of local electromyography. The AP duration of the gastrocnemius decreased by 27% on the average, and of the tibial muscle--by 38% in comparison with the normal age values. There was no direct dependence between the reduction of the AP duration of the gastrocnemius and the tibial muscle MU on the spinal cord affection level, the posttraumatic period duration, and the spastic syndrome expression. Changes in the AP duration of the MU were apparently due to different degree of the atrophic process resulting from prolonged adynamia.


[Monoamine content in the motor region of the cerebral cortex following damage to the symmetrical area of the opposite hemisphere]. On 8 cats chronic experiments were carried out to determine (spectrofluorometrically) the content of serotonin, dopamine, and noradrenaline in the sigmoid region of the left cerebral hemisphere on the second, third, forth, fifth, eighth days after the removal of the cortex of the symmetrical region of the right hemisphere. On the second day, at the time of maximum disorders of the locomotor function, dopamine content was found to decrease; there was also a tendency to reduction of noradrenaline and serotonin. On the third, and the fifth--eighth days, at the period of the locomotor activity restoration, there was a rise of serotonin content, whereas dopamine content remained low, and noradrenaline content rose considerably. The role of biochemical changes in the motor region in the mechanisms of locomotor function restoration following symmetrical damage of the large hemisphere cortex is discussed.


[Effect of prostaglandins E1 and E2 on the internal carotid artery]. Experiments were conducted on the dog internal carotid artery (with circulatory isolation); the following peculiarities of the effects of the prostaglandins (PG) under study were revealed: PG-E1 caused either a constrictory or a dilatory effect, and PG-E1--a constrictory effect only; in the former case the artery became accustomed with repetition of the action, and in the latter case it did not become accustomed. The duration of the PG-E2 effects, particularly of relaxation, was much greater than of the serotonin effects; residual contraction of the vascular smooth muscles was frequent; PG-E1 and PG-E2 intensified the effects of serotonin, and, partially, of noradrenaline.


[Effect of peridural blockade of the heart on the ventricular fibrillation threshold in dogs]. Experiments were conducted on dogs with determination of the ventricular fibrillation threshold in animals with intact heart and with myocardial infraction in case of trimecaine injection into the peridural space at the T1--T2 level. The fibrillation threshold was elevated both on account of resorptive trimecaine action and due to the block of the sympathetic heart innervation.


[Formation of hemodynamic pulmonary edema in irradiated bodies]. Experiments on albino rats demonstrated that high doses of ionising radiation producing pronounced leukopenia increased the animal resistance to pulmonary edema under the effect of adrenaline. This effect was especially manifest on the 4th day of irradiation. Relatively low doses (up to 100 r) as well as separate irradiation of the head, chest, or the abdomen induced pulmonary edema.


[Temperature reaction and survival of experimental animals exposed to microwaves of different intensity]. Changes of the rectal temperature during the day were determined in CBA mice and Wistar rats subjected to the total body irradiation with microwaves of different intensity. Dependence of these indices on keeping the animals in containers for irradiation and temperature reactions, and survival of the animals after exposure to UHF microwaves of various intensity were investigated. As shown, temperature rise and survival of the animals depended on the current intensity density and the action duration, the rectal temperature elevation during the irradiation; a pronounced reduction of this index following irradiation may be considered as a prognostic sign of affection with the UHF microwave field.


[Long-term exposure of rats to high concentrations of carbon dioxide]. The authors studied the isoenzymatic spectrum of lactic dehydrogenase of the myocardium, the frequency of cardiac contractions and ECG during the action of high carbon dioxide concentration, and also the survival of rats depending on the speed of carbon dioxide concentration increase in the atmosphere. Functional changes noted in the cardiac activity during the carbon dioxide action (concentration 30%, 7 1/2 hours) were not accompanied by any disturbances of carbohydrate metabolism in the myocardium. The most important condition for the survival of rats subjected to the action of high carbon dioxide concentration (up to 50% in the atmosphere) was the speed of elevation of this concentration.


[Mechanism of the decrease in basal metabolism during adaptation to hypoxia]. Oxygen uptake fell by 40% in rat adaptation to the periodic action of hypoxia under conditions of pressure chamber. This phenomenon did not disappear in animals in the state of profound anesthesia, and, consequently, was independent of adaptation changes of the cortical regulation of the animal motor activity. A cut of oxygen uptake by half persisted with the action of cold, noradrenaline, and 2,4-dinitrophenol, uncoupling oxidation and phosphorylation, on the organism. Thus, economic expenditure of oxygen in hypoxia adaptation could not be fully explained by increase of oxydation and phosphorylation conjugation.


[Role of intestinal hormones in the pathogenesis of experimental pancreatitis]. In acute experiments on dogs with preliminarily induced pancreatitis the authors traced disturbances of the secretory reactions of the pancreas in response to adequate stimulation with the intestinal hormones. There was a reduction in the activity of complex intestinal hormones preparations obtained from the duodenal mucosa at the acute period of the disease in these dogs. In chronic experiments there was found an increase of acid production debit in the stomach and a shift in the duodenal contents reaction in the acid direction in pancreatitis. A conclusion was drawn on an important pathogenetic role played by the intestinal hormones in the mechanism of disturbances of the pancreatic exocrine secretion in pancreatitis.


[Effect of Ca2+ and gamma-aminobutyric acid on glutamate and glutamine oxidation by rat brain synaptosomes]. It was shown in vitro that Ca2+ addition induced inhibition of the synaptosomal respiration with glutamate and glutamine. The presence of GABA in the medium increased the inhibitory effect of Ca2+ on glutamine oxidation, but not on glutamate. GABA, by itself, had no influence on both glutamate and glutamine oxidation.


[Effect of acute cardiac ischemia on the activity of the protein synthesizing system of the internal membranes of myocardial mitochondria]. The effect of acute experimental heart ischemia on protein synthesis and RNA of the internal membranes of myocardial mitochondria was studied; there was a sharp increase in the protein synthesizing system activity of the internal mitochondrial membranes. The most pronounced protein and PNA exchange was noted on the 7th day of the infarction; apparently it was the most critical time in the development of the given pathological process. A study of ultrastructure of mitochondrial membranes in the course of experimental infarction development demonstrated marked changes in their ultrastructure depending on the severity of the disease.


[Glucose-6-phosphate dehydrogenase of neurogenically damaged heart]. Neurogenic damage of the myocardium by electrostimulation of the aortic arch led to deficiency of tissue noradrenaline (the sympathetic nervous system mediator). Simultaneously there was a marked rise of the glucose-6-phosphate dehydrogenase activity. Preliminary administration of the RNA synthesis inhibitor--actinomycin D--fully prevented the increase of this enzyme activity in the myocardium produced by its neurogenic damage. The data obtained testified to the acceleration of induction of this enzyme in the myocardium in case of its neurogenic damage, this correlating with the change of tissue noradrenaline balance.


[Effect of imipramine-like antidepressants on head shaking induced by 5-hydroxytryptophan in mice]. In the reaction of head twitching (HT) in mice in response to 5-oxytryptophan administration in the capacity of a serotonergic model antidepressants chlorimipramine and imipramine and also chlorpheniramine (suprastin) expressed a serotonopositive action in doses of 1.0, 5,0, and 1.0 mg/kg, respectively. Quiprazine produced a serotonomimetic action. Desipramine exerted abmivalent activity in doses of 1.0--20.0 mg/kg, whereas iprindol and morphaphen were ineffective in doses up to 20.0 mg/kg. Amitriptyline, noveril, melitracene, trimipramine, and ludiomil inhibited HT in doses of from 0.5, 1.0, 20.0, 20.0, and 20.0 mg/kg, respectively. The results are discussed in the light of the concept on the complex "neurotransmitter activity" spectrum of imipramine-like antidepressants.


[Effect of pharmacologic substances on the dominance-submission relationship in a pair of rats]. The effect of neuroleptics (chlorpromazine, trifluoperazine, haloperidol), antidepressants (amitryptyline, imipramine), tranquilizers (diazepam, chlordiazepoxide, benactyzine) and stimulant d-amphetamine on the domination and subordination relations formed as a result of competitive behaviour in a pair of rats was studied. The drugs in question proved to violate the set relations of domination and subordination weakening the attacking ability of dominating rats and strengthening the defensability of the subordinate ones. With increase of antidepressants dosage received by a subordinate rat its competing ability becomes enhanced too; this may cause a change in domination.


[Effect of adrenergic blockade on autoregulation of cerebral blood flow during orthostatic tests]. The effect of phentolamine and anapriline on the cerebral blood flow autoregulation (CBFA) under the orthostatic test (OT) was studied in experiments on locally anesthetized rabbits. Cerebral blood flow (CBF) in the carotids, venous pressure in the cerebral vessels, perfusion pressure (PP) in the carotid arteries were measured, the resistance of cerebral vessels was calculated. OT was modeled by tilting a special table with the animal (with its head upwards or a special table with the animal (with its head upwards or downwards) by 40--80 degrees from the horizontal level. The results showed adrenergic block in most of OT cases to disturb CBFA; phentolamine promoted passive increase of CBF when PP was increased; on the contrary, anapriline promoted passive CBF reduction when PP was decreased.


[Selective inhibition of the tonic component of portal vein smooth muscle cell potassium contracture by verapamil]. The studies were performed on the rat portal vein smooth muscle cells, using double sucrose-gap method. 10(-9)--10(-7) M-verapamil was shown to selectively block the tonic component of potassium contracture. Since potassium depolarization of the membrane persists, it may evidence that verapramil had a specific effect on the excitation-contraction coupling by blocking the passive calcium entry into the muscle cells. At higher concentrations (10(-6)--10(-5) M) verapramil produced inhibition of the phasic component of potassium contracture by blocking the potential-dependent calcium canals of the portal vein smooth muscle cell membrane responsible for generation of the action potentials.


[Role of vascular thermoreceptors in the mechanism of cold tremor inhibition by oxotremorine, seduxen and phentolamine]. Intravenous infusion of oxotremorine, seduxene, and phentolamine to cats not only decreased the cold-induced tremor, but also reduced the subcutaneous vein receptor impulses. Diminished activity of the vascular thermoreceptors served as an additional component in the mechanisms of the inhibitory effect of oxotremorine and seduxene on cold tremor. Reduction of the thermoreceptors activity after phentolamine administration is primary, and may be considered as the leading factor in the cold tremor inhibition.


[Effect of Krebs cycle intermediates on the blood supply and energy metabolism of ischemic myocardium]. The influence of d-ketoglutarate and succinate in acute experiments on dogs was studied by the following parameters: collateral coronary circulation (CCC) of the ischemic myocardium, systemic arterial pressure, and the content of lactic, pyruvic acids, and glucose in the blood flowing from the ischemic zone. alpha-ketoglutarate (6 mg/kg intracoronary and 60 mg/kg intravenously) proved to produce a positive effect on CCC and the contractile activity of the myocardium. Intravenous injection of alpha-ketoglutarate (12 mg/kg) and succinate (100 mg/kg) decreased significantly the consumption of glucose by the ischemic myocardium which rose after the ligation. In comparison with alpha-ketoglutarate, all doses of succinate were more effective as a factor of preventing the increase of lactic acid in the blood flowing from the ischemic zone. Thus, definite doses of alpha-ketoglutarate and succinate could be used for pharmacological correction of CCC and energy supply of the ischemic myocardium.


[Glucose tolerance and insulin sensitivity of rats poisoned with amanita-phalloidines]. The effect Amanita phalloides on glucose tolerance and insuline sensitivity was studied. Amanita phalloides toxins were injected to albino male rats intraperitoneally in a dose of DL50. Amanita phalloides proved to cause disturbance of glucose tolerance, increased tissue glucose utilization, and enhanced the organism insuline sensitivity. The mentioned effects result from a decrease of insuline-inactivating capacity of the liver and from enhanced function of the insuline apparatus of the pancreas.


[Effect of normal microflora, age and sex of rats on serum IgG2 levels]. Germfree and conventional rats of Fisher inbred strain and mongrel animals were used in this study. IgG2 was separated from the pool serum of mongrel rats, and anti-IgG2 was obtained by hyperimmunization of rabbits. IgG2 content was determined by in the sera of different groups of rats radial immunodiffusion. There was 5.4 times less IgG2 in the sera of Fisher germfree rats than in conventional Fisher animals; its level in female animals was by 10--15% higher than in the male ones. The first hours after birth the IgG2 level was the same in the sera of all the newborn rats irrespective of its amount in the maternal sera.


[Protective effect of several diphosphonic compounds against damage to lymphocytes by antilymphocyte serum]. Rabbit antilymphocytic serum and complement were taken in quantities provoking the death of 50 per cent of human lymphocytes secreted in the phycol-verographin density gradient. Compounds (dinatrium salt of oxyethylendiphosphonate acid, alkylated oxyethylendiphosphonate acid, aminoethyloxyethylendiphosphonate acid, aminobenzyldiphosphonate, and aminoisopropyldiphosphonate acids) of 10 mM diphosphonic composition solutions in quantities of from 0.001 ml to 0.2 ml were added to experimental samples of 0.2 ml lymphocytes suspension containing 2.4 X 10(4)--6.0 X 10(4) cells. A decrease in the dead cell count in staining with a 0.1 per cent trypan blue solution was observed. Dinatrium salt of oxyethylendiphosphonate acid and alkylated oxyethylendiphosphonate acid proved to be most effective: it showed protective properties already in a dose of 0.01 ml. All the tested components had a pronounced protective action in a dose of 0.1 ml.


[Effect of DL-tryptophan on blastomogenesis induced by acrylic plastic]. Plastic plates implanted subcutaneously to rats induced sarcoma in 11 of 27 animals (40.7%) which survived up to the time of the first tumour appearance (12.3 months). No tumours were revealed at the sites of the plastic powder implantation. Following long-term administration of DL-tryptophan tumours developed around the plates in 6 to 19 rats (31.5%) in 13.8 months, and around the powder in 2 of 5 rats which survived for 18.7 months. Some animals of this group displayed preneoplastic changes around the powder clumps.


[Effect of marrow cavity curettage on bone marrow stromal cell precursors]. Changes in the number of bone marrow stromal precursor cells of guinea pigs after the bone marrow curettage was studied by cloning in monolayer cultures in vitro. About half of the colony-forming units (CEU-F) is extracted during curettage. Later the number of CFU-F in the curetted bone marrow continues to fall, reaching its minimum in 12 hours. Regeneration begins after 24 hours, and on the 7th--12th day the CFU-F content in the curetted bone marrow reacts the normal level; by the 20th day the number of CFU-F exceeded the normal 2.5 times. The CFU-F content in the contralateral bones of donors exceeded their normal content (at periods from 6 hours to 20 days) 2--2 1/2-fold.


[Formation of DNA--protein crosslinks and their possible elimination in cultures of normal human fibroblasts after exposure to embichin]. New methods of radiometry and fractionation of cell lysates on hydroxyapatite were applied to determine the crosslinkage between DNA and protein induced by embiquin in cell culture of normal human skin fibroblasts. Such crosslinks were found to be formed; they were eliminated in long-term cultivation of the cells after mutagen treatment.


[Limits of several cell nucleus reactions in old age and in the presence of a pathological process]. The number of nucleoli and the structure of nucleolus-associated chromatin (determined by the number of perinucleolar chromocentres) was investigated in two groups of mice. The first group was control, and the second one--experimental, given CCl4 injections once a week, for one year. A gradual increase of the number of nucleoli and chromocentres bound with nucleoli was revealed with ageing in control mice. In the experimental group both indices quickly reached the maximum which was equal or even higher than in old control mice. The subsequent development of the pathological process failed to alter these indices. Possible mechanisms limiting the range of the mentioned changes of the nuclei are discussed.


[Morphologic analysis of the specialized cardiomyocytes of the heart conduction system of vagotomized rats]. The specialized conduction system of the rat heart was studied by light and electron microscopy at various periods following vagotomy. The dynamics of tissue and cellular alterations is described. Variegation of the cellular reactions at all the postdenervation periods for all the conduction system parts and for all types o specialized cardiomyocytes was revealed.


Atypical lymphoid leukemia in ataxia telangiectasia. We observed two sisters with ataxia telangiectasia, one of whom developed an atypical subacute lymphocytic leukemia characterized by atypical lymphocytes and absence of palpable lymphadenopathy or hepatosplenomegaly. The lack of organomegaly in this patient may have been due to the underlying ataxia telangiectasia, which was associated with lymphoid hypoplasia. Cytogenetic studies showed a marker chromosome 14 [t(14q11:14q34)] in both patients. The sister with leukemia had other complex chromosomal aberrations in addition to the marker chromosome 14 that were stable for more than 14 mo before the patient's death from complicating infection. The development of atypical T cell leukemia has not been previously described in ataxia telangiectasia. This case further illustrates the interesting interrelationships amoung immunosuppressed states, development of lymphoid malignancy, and an emerging pattern of a propensity to chromosome 14 abnormalities in various lymphoid malignancies.


Postmitotic marrow neutrophils and neutrophil mobilization in man: role of the spleen. The relationship between postmitotic marrow neutrophils (PMMN) and neutrophil increment in blood after an intravenous dose of 3 mg hydrocortisone/kg was studied in patients with normal-sized spleens and compared with splenectomized and splenomegalic patients. PMMN were quantified from the ferrokinetic measurement of the normoblast number and the PMMN/normoblast ratio in bone marrow biopsy sections. In 12 control patients with normal PMMN the increment was 3.50 +/- 1.13 X 10(9) neutrophils/liter. An excellent correlation was found between the number of PMMN and the maximal neutrophil increment (y = 826x - 1021, r = 0.93, p less than 0.001) among 24 patients with normal spleen size and a wide range of marrow cellularity. Significantly higher responses were observed in 10 splenectomized patients (y = 872x + 1429, r = 0.92, p less than 0.001). The two regression lines were shown to be parallel, indicating a diminution of the response by 2.5 X 10(9) neutrophils/liter in the presence of a normal spleen. In 11 hypersplenic patients the responses were further reduced and more variable. Peak neutrophilia occurred after median values of 2, 3, and 4 hr in the hypersplenic, the control, and the splenectomized group, respectively. These studies indicate that allowing for the different response curves neutrophil increments may be used as an index of PMMN in patients with normal spleen size and in splenectomized patients. They further suggest sequestration of the prematurely released cells by the spleen.


Monoclonal IgG anticoagulants delaying fibrin aggregation in two patients with systemic lupus erythematosus (SLE). There is paucity of information regarding the prolonged plasma thrombin time known to occur in some patients with systemic lupus erythematosus. Detailed investigations of plasma from two such patients disclosed that IgG accounted for this defect in each case. IgG isolated from plasma of either patient possessed the property of delaying fibrin aggregation and prolonging the clotting times of fibrinogen. Preincubation of IgG from either patient with anti-IgG or anti-Fab (rabbit) serum abolished this anticoagulant property. Moreover, the anticoagulant IgG from the first patient was neutralized with anit-k chain and anti-IgG3, that from the second patient with anti-lambda chain and anti-IgG1 serum. These anticoagulants were also dissimilar with respect to their interactions with fibrin(ogen). IgG from the first patient had no anticoagulant activity against fibrin(ogen) species lacking intact Aalpha chains. IgG from the second patient displayed undiminished anticoagulant effect on such fibrin(ogen) species. We conclude that each anticoagulant interacted with a distinct region(s) on the fibrinogen molecule and that these interactions affect or involve sites that participate in the fibrin self-assembly process.


Simple electrophoretic system for presumptive identification of abnormal hemoglobins. By the International Committee for Standardization in Hematology. In order to determine if mutant hemoglobins can be identified by relatively simple methods, a Working Group of the ICSH Expert Panel on Abnormal Hemoglobins and Thalassemia analyzed 17 hemolysates containing 14 different mutant hemoglobins by four electrophoretic methods: (1) cellulose acetate in alkaline buffers, (2) citrate agar pH 6.0, (3) urea 2-mercaptoethanol buffer pH 8.9, and (4) urea 2-mercaptoethanol buffer pH 6.0. The examined mutants included several of great numerical and clinical importance as well as some rare ones, namely, HbS, C, D Los Angeles (Punjab), E, G Philadelphia, N Baltimore, and O Arab; also Hb Ft. Worth, Montgomery, Winnepeg, Rush, Q India, Bethesda, and Lepore. Comparative mobilities of these hemoglobins in all of the methods are presented here. The combined data permit their presumptive identification, often with a high degree of specificity. The system has been applied in Iran, where the four prevalent mutants can be differentiated by these methods, at considerable saving of time and resources previously expended on structural analyses. It is proposed as a basis for an ICSH Tentative Standard. There is little doubt that this presumptive identification of hemoglobin variants by simple electrophoresis will be improved or complemented by the introduction of newer techniques, such as immunologic analysis. However, for the present and for some time to come, the system outlined here should be found valuable. The present report does not concern itself with the numerous auxiliary techniques involved in the identification of abnormal hemoglobins-sickle-cell test, solubility tests, lability test--and no claim is made that the simple system described here eliminates these other techniques from the diagnostic armamentarium of the laboratory.


Sex differences in the antithrombotic effects of aspirin. Aspirin inhibits platelet function by acetylating platelet cyclooxygenase. Recent clinical trials indicate that aspirin is a promising antithrombotic agent against both venous and arterial thrombosis, but somewhat surprisingly this protective effect appears to be limited to males. To examine the potential sex-related differences in response to aspirin, we developed an animal model for quantitating fibrin accretion into an injury-induced thrombus and used it to study the effects of aspirin on thrombus size in male and female rabbits. Platelet prostaglandin synthesis was estimated by assay of platelet malondialdehyde and was significantly decreased in both male and female rabbits following treatment with 10 mg/kg aspirin (p less than 0.001). This inhibitory effect was not different for platelets from male and female rabbits. Thrombus size was significantly decreased in aspirin-treated male rabbits when compared to controls (p less than 0.05), but this aspirin effect was not apparent in female rabbits or rabbits of either sex treated with 10 mg/kg sodium salicylate. These findings support the results of clinical trials that were obtained by retrospective subgroup analysis. The reason for the sex difference is not known, but the findings raise an important issue in relationship to this mechanism of the antithrombotic effect of aspirin.


Deletion of the long arm of chromosome 20 [del(20)(q11)] in myeloid disorders. Detailed clinical and cytogenetic studies were performed in five patients who had abnormal hematopoiesis and an acquired deletion of an F-group chromosome. Cytogenetic analyses, with banding techniques, of cells from bone marrow, spleen, or unstimulated peripheral blood showed a partial deletion of the long arm of one chromosome 20 [del(20)(q11)] in all five patients. Three patients had myeloproliferative disorders of uncertain classification, the fourth had possible preleukemia, and the fifth had acute myelomonocytic leukemia. Although the five cases showed certain similarities, the clinical and hematologic findings seen with the 20q- abnormality were not specific. None of the patients showed evidence of polycythemia vera or idiopathic acquired refractory sideroblastic anemia, two diseases previously associated with the 20q-. Our studies indicate that the 20q- abnormality is not limited to diseases primarily affecting erythropoiesis but that it can be found in the broader spectrum of myeloid disorders. In polycythemia vera, the 20q- has sometimes been regarded as a possible result of previous therapy with cytotoxic agents; however, four of our patients were untreated when the deletion was first noted.


Adriamycin and daunomycin generate reactive oxygen compounds in erythrocytes. Adriamycin and daunomycin produce dose-related cardiac toxicity that may be related to oxygen radicals. Addition of these compounds to human erythrocyte suspensions resulted in stimulation of hexose monophosphate shunt activity that was markedly impaired in the absence of oxyhemoglobin. Evidence for generation of hydrogen peroxide by these compounds was provided by oxidation of reduced glutathione, by 14C-formate oxidation, and by the catalase-aminotriazole trapping technique. These experiments indicate that Adriamycin and daunomycin interact with oxyhemoglobin to generate reactive oxygen metabolites. A similar interaction with oxymyoglobin may occur in the heart and produce oxygen radicals that injure cardiac myocytes.


Effect of C3b inactivator on monocyte-bound C3-coated human erythrocytes. As a model of IgM-induced hemolytic anemia in man, human erythrocytes were sensitized with IgM antibody and coated with complement components, including C3 and C4, using human serum as a source of complement. These coated red cells were then interacted with monolayers of human mononuclear phagocytic cells (monocytes). Complement-coated red cells so bound could be displaced from their monocyte attachment site in a dose- and time-dependent manner by serum factors, including C3b inactivator (C3bINA). These factors were more efficient in inactivating red cell-bound complement components prior to interaction of the coated cells with monocytes. With large amounts of complement per erythrocyte, measured as membrane-bound C3, the ability of the serum inactivating factor(s) to remove the complement-coated red cells from the monocyte surface was compromised and persistently bound red cells were progressively phagocytosed. These studies implicate C3bINA in the displacement of complement-coated erythrocytes, formed from the interaction of IgM antibody and serum complement, from the hepatic macrophage in IgM-induced immune hemolysis. They suggest that both the concentration of complement components, especially on the erythrocyte surface, and the level of C3bINA and perhaps other inactivators may be important features regulating hemolysis in this disorder.


Correlation of serum IgD level with clinical and histologic parameters in Hodgkin disease. The concentration of serum IgD was measured in 100 patients with Hodgkin disease; 65 had 3--50-fold increases in IgD levels. Several parameters were found to influence serum IgD concentration: IgD level in older patients (greater than 50 yr) was significantly lower than in the younger patients (P less than 18 yr). IgD concentration was significantly higher in splenectomized than in nonsplenectomized patients (p less than 0.005). Therapy was found to depress IgD concentration, which fell to a value significantly lower than in untreated patients (p less than 0.05). An interesting correlation was found between IgD levels and histologic type of the disease, lower levels being preferentially associated with the lymphocyte predominance type and higher with the lymphocyte dipletion type. The logarithms of the means of these two groups were significantly different from the overall mean of the disease (p less than 0.05 and p less than 0.0005, respectively). Mixed cellularity and nodular sclerosing showed intermediate values.


Expression and specificity of FcIgG receptor sites on neoplastic lymphocytes. We investigated the ability of an FcIgG receptor marker to discriminate between subtypes of malignant lymphoproliferative diseases that differed in their clinical presentations. A quantitative radioimmuno assay was established that enabled us to evaluate average receptor densities on a population basis. Surface receptors were first saturated with IgG complexes. The number of membrane associated IgG molecules was subsequently determined with 125I-staphylococcal protein A. Results obtained with this assay on a battery of malignant lymphocytes suggested that the range of receptor densities of malignant B and T cells might overlap each other but would correlate with the degree of tumor cell differentiation and the clinical stage of the underlying disease. This behavior limits the use of this marker in the characterization of the derivation of malignant lymphocytes; these findings, however, may be useful in the prognostic classification of lymphomas of known origin.


Activation of factor X by factors IXa and VIII; a specific assay for factor IXa in the presence of thrombin-activated factor VIII. We studied the activation of factor X by the intrinsic pathway of blood coagulation using a new assay of factor X activation. When factor X tritiated in its sialic acid residues is activated, activation can be measured by the release of tritiated activation peptide, and the initial rate of activation can be determined under varying conditions. In the presence of phospholipid and calcium ions, factor IXa activated factor X slowly without factor VIII, and this activation was blocked by a specific factor IX inhibitor. These data provide strong evidence that factor IXa is the enzyme responsible for factor X activation by the intrinsic pathway. The role of factor VIII was also investigated. Factor VIII could be reproducibly thrombin activated and then stabilized by the addition of 2 mM benzamidine hydrochloride; this suggests that inactivation is due to proteolysis. Neither unactivated nor thrombin-activated factor VIII produced factor X activation without factor IXa. With a constant level of factor IXa, factor X activation was directly proportional to the level of activated factor VIII. With a constant level of activated factor VIII, factor X activation was proportional to the factor IXa concentration. This observation was exploited to develop a specific, sensitive assay for factor IXa.


Autoimmune cytotoxic granulocyte antibodies in normal persons and various diseases. Of 400 female and 58 normal nonommunized male sera approximately 10% were cytotoxic for a panel of allogeneic granulocytes. Sera with strong alloreactivity were also autoreactive, which emphasized the large autoimmune component of most alloantisera against granulocytes. The cytotoxic granulocyte autoantibodies were complement dependent, of the IgM class, and exhibited optimum cytotoxic activity in vitro at 5 degrees C precomplement incubation temperatures with papain-treated cells. The sera were unreactive with autologous or allogeneic B and T lymphocytes, monocytes, and red blood cells but were cytotoxic for adult and cord granulocytes, eosinophils, and chronic myeloid leukemia cells. Granulocyte autoantibodies were present in 53% of sera from 57 patients with systemic lupus erythematosus (p less than 0.00002) but were not found in increased frequency in the sera of patients with 28 other diseases. We conclude that a single tissue-specific antigenic determinant(s) called "G" may be present on granulocytes and is the target of naturally occurring autoantibodies.


Release of arachidonic acid from human platelets. A key role for the potentiation of platelet aggregability in normal subjects as well as in those with nephrotic syndrome. Low (nonaggregating) concentrations of collagen that potentiate platelet aggregation did not induce the formation of measurable amount of malondialdehyde (MDA) but released small but significant amounts of radioactivity from 14C-arachidonic acid-labeled platelets. A major portion of the radioactive compounds released by nonaggregating concentrations of collagen existed as arachidonic acid and a minor part as thromboxane B2. The nephrotic syndrome enhances platelet aggregability, and this effect is abolished by correcting hypoalbuminemia in vitro and in vivo by the addition of albumin, which is the main carrier for free fatty acids, including arachidonic acid. Human albumin (fatty acid free) inhibited collagen-induced aggregation, MDA formation, and release of the radioactivity from 14C-arachidonic acid-labeled platelets in normals as well as in those with nephrotic syndrome. These data support our hypothesis that the main mechanism responsible for the potentiation of platelet aggregation is the release of arachidonic acid from platelet membrane phospholipids via the activation of phospholipase A2. Furthermore, enhanced platelet aggregation in the nephrotic syndrome was at least partly attributable to an increased availability of arachidonic acid released secondary to hypoalbuminemia. Albumin inhibits aggregation probably by binding to released arachidonic acid preventing arachidonic acid from being metabolized to potent aggregating substances, endoperoxides and thromboxane A2. The mechanism of release of arachidonic acid may play a key role in the potentiation of platelet aggregability in normals as well as in pathologic conditions such as the nephrotic syndrome.


Coupled amidolytic assay for factor VII: its use with a clotting assay to determine the activity state of factor VII. A coupled amidolytic assay for factor VII (VII) has been developed that when used with a clotting assay for VII enables detection of activated VII. In the assay, VII in a test material determines generation of factor Xa in a mixture of purified factor X, tissue factor, and calcium; factor Xa is measured with a chromogenic substrate. Factor VII activity in the coupled amidolytic assay (VIIam) correlated well with VII activity in a one-stage clotting assay (VIIc) in 57 healthy subjects, 5 patients with hereditary VII deficiency, and 11 patients with liver disease. Activation of plasma VII by kaolin, clotting, or cold strikingly increased VIIc but not VIIam levels. Thus the ratio VIIc/VIIam (VII activity ratio) is a measure of VII activation. In 27 warfarin-treated patients the mean VII activity ratio was significantly decreased, reflecting a greater decline in VIIc than in VIIam. This probably stems from partially carboxylated VII being able to act during the 3-min incubation of the amidolytic assay but unable to act rapidly enough to affect the clotting assay. Measurement of VIIc/VIIam should enable evaluation of the activity state of VII in thrombotic disorders and in components for transfusion therapy.


Studies on the target cell for the Friend virus (FV-P strain) using the CFU-E technique. In order to characterize the target cell for the polycythemia inducing Friend virus (FV-P) in vivo, mice were treated by induction of plethorism, bleeding, Actinomycin D, and Busulfan before virus infection. The development of the Friend leukemia was then studied mainly using the CFUE technique for erythroid colony growth in vitro. This technique allows the quantification of a new cell type, an erythropoietin (Ep) independent colony forming cell. These Ep independent colonies were taken as marker for the disease. Their number with time after infection was correlated with the compartment size of pluripotent, granuloid committed and erythroid stem cells at the time of infection. The results indicate that the development of the Friend leukemia does not require the actual presence of CFUE, as seen using Actinomycin D, and is not correlated with the number of pluripotent or granuloid stem cells, as seen after Busulfan. It is, however, dependent on the erythropoietic state of the animal, as seen in plethoric mice and mice after bleeding. It is, therefore, concluded that the target cell for FV-P is located within the Ep-responsive cell compartment, between early (BFUE) and late (CFUE) erythroid precursor cells.


Rabbit anti-mouse brain serum (RAMBS): lack of specific inhibition of late committed erythroid stem cells in culture (CFU-E). Heterologous antisera to mouse brain tissue have activity against mouse pluripotent hemopoietic stem cells (CFU-S), but not against granuloid/macrophage committed precursor cells (CFU-C). In these studies we show that anti-mouse brain serum raised in a rabbit does not possess specific activity in vitro against late committed erythroid stem cells (CFU-E).


Influence of acetaldehyde, dietary protein, carbon tetrachloride and butylatedhydroxytoluene on the toxicity of methylmercury in rats. The influence of environmental or dietary factors on the toxicity of methylmercury (MeHg) was investigated due to possibilities that humans exposed to methylmercury may have been sensitized. Groups of 8 rats were exposed to 0, 20 or 40 ppm MeHg in a semisynthetic diet and fed 0.5% BHT, 5% protein (instead of 15%), or injected with 250 mg/kg CC14 or acetaldehyde. In control rats neurotoxicity occurred at 4 weeks and 9 weeks with 40 and 20 ppm MeHg, respectively. Mortality was observed at 6 weeks with 40 ppm and 1 rat died in week 9 with 20 ppm MeHg. Acetaldehyde injected rats died at week 4 and 6 when fed 40 or 20 ppm MeHg. Neurotoxicity was observed in week 3 and 5 in these groups, respectively. Treating rats with the low protein or BHT accelerated neurotoxicity and mortality by 1 week with 40 ppm MeHg. These agents had killed all test animals within 7 weeks at 20 ppm MeHg. Neither acetaldehyde nor BHT influenced 0 ppm MeHg controls while 5% protein induced precipitous weight loss. In the case of CC14, the rats lived longer in combination experiments than one would have expected from the individual treatments.


Potentiation of methylmercury toxicity by piperonyl butoxide. Methylmercury (MeHg) is an extremely potent neurotoxin about 25% of which is degraded in vivo to inorganic mercury. Piperonyl butoxide (PB) is a widely used pesticidal synergist which inhibits many mammalian detoxification reactions. In a preliminary experiment with the high doses of PB and MeHg, PB induced a 12% decrease in mean survival time and a 20% decrease in mean latency time to neurotoxicity. The weight loss in PB-MeHg group was far greater than the control MeHg group. In a dose response experiment, mean survival times in rats fed 40 ppm MeHg-C1 were 5.75, 5.3, and 5.0 weeks at 0, 0.5, and 1% PB, respectively. By the ninth week 25% of rats fed 20 ppm MeHg-C1 showed neurotoxicity and 63% of the 0.5% PB fed showed neurotoxicity with some mortality. In experiments at 20 ppm MeHg-C1 both  PB fed groups weighted considerably less than corresponding controls.


Residues of Dacthal herbicide in carrots. Residues of Dacthal and its monoacid and diacid hydrolytic ester cleavage metabolites were determined in carrots to which the herbicide was applied on seven plot locations throughout the United States. Residue levels of Dacthal appeared more closely related to the rate of application than to other field parameters. Traces of the monoacid metabolite were found in a few samples. The diacid metabolite was not detected in any of the samples.


The toxicity of manganese ethylenebisdithiocarbamate to the adult newt, Triturus cristatus. The toxicity of ethylenebisdithiocarbamate (maneb), a widely used agricultural fungicide, to the adult newt (Triturus cristatus carnifex) was evaluated after percutaneous exposure. Maneb was lethal to all the animals at the 50 ppm level within fifteen days. Male newts seem to be less resistant to the toxicant than females. At concentrations as low as 25 ppm all males died within 25 days, whereas some of the females were still alive after 5 months. Microscopic examination showed that the skin and the kidney were the most severely affected organs. It has been hypothesized that an osmoregulatory breakdown and an impairment of cutaneous respiratory exchanges play a role in the death of the animals. Renal failure must also be taken into account. However, additional mechanisms can not be ruled out at present.


Localisation of speech through similar and dissimilar binaural hearing aid listening modes. This  paper compared the localisation abilities in the horizontal plane of 12 adults with bilateral asymmetrical sensorineural hearing impairment whilst listening to speech using each one of the following three binaural hearing aid listening modes: (a) binaural listening with two similar ear-level hearing aids, (b) binaural listening with two similar bodyworm hearing aids and, (c) binaural listening with two dissimilar hearing aids (one ear-level, one bodyworn). It was found that the differences in localisation ability between the three binaural hearing aid listening modes were small and none of them proved to be statistically significant. It was concluded that where possible binaural hearing aids should be of similar type and model, although in situations where this could not be achieved or was not indicated, the issuing of dissimilar binaural hearing aids should not be discouraged.


Differences in brainstem response latency with age and sex. Brainstem evoked potentials in response to clicks at 60dB, 70dB and 80dB were recorded from a group of 70 normally hearing subjects. There were 10 subjects (5 male, 5 female) for each of the decades from the second to the eighth. The youngest subject was 14 years, the oldest 79 years. The possibility of there being increased latencies as a function of age was examined. The results indicated that there was, for practical purposes, no such increase. On the other hand there was very strong evidence that in females latenceis are shorter than in males. In addition, amplitudes were reduced in the case of older subjects. Condifidence limits for latency were calculated. These may be helpful in deciding whether or not a particular latency is outside the normal range.


Some observations on the contralateral stapedial reflex artefact. An artefact was observed whilst testing profoundly deaf children with a peters AP61c acoustic impedance meter, using the contralateral stapedial reflex technique at high stimulus levels. A study was carried out on cadavers which confirmed the earlier observation, and this pseudo-reflex was found to be caused by the transmission across the head of the stapedial reflex stimulus tone during contralateral testing. An electronic filter was designed and built which suppressed this artefact. It is suggested that this artefact could be mistaken for a stapedial reflex response.


Speech recognition with dynamic range reduction: (1) deaf and normal subjects in laboratory conditions. Processing to reduce the dynamic range of speech should increase intelligibility and protect the impaired ear from overloading. There are theoretical and practical objections to using AGC devices to reduce dynamic range. These are overcome by using recently available signal processing employing high frequency carrier clipping. An increase in intelligibility of speech with this HFCC has been demonstrated, for normal subjects with simulated deafness, and for most partially hearing patients. Intelligibility is not improved for some patients; possibly due to their having learned to extract features which are lost. These patients may also benefit after training.


Evaluation of a breast-feeding campaign in Trinidad. There has been a marked decline in breast-feeding throughout the developing world. It is generally agreed that this trend should be reversed, and that in achieving this objective mass communication media could play an important role. The present article analyzes the results of a campaign to promote breast-feeding in which the press, television, and radio were used. It is hoped that this analysis will prove useful for other individulas and groups that may wish to plan similar campaigns.


Environmental health and technical cooperation among developing countries. The subject of technical cooperation between developing countries has attracted growing attention in recent years. The account presented here summarizes PAHO's efforts to promote such cooperation in the field of environmental health.


Immunization against leptospirosis: continued vaccine trials in hamsters using strains isolated from Barbados. Heated whole-cell suspensions of L. interrogans serotype copenhageni strains isolated from the field in Barbados have proved to be protective immunogens against experimental leptospirosis.


Serologic survey of dengue and other arboviruses in Curaçao and Aruba, 1973. Sera obtained principally from children on the Caribbean islands of Aruba and Curaçao were tested for antibodies to various arboviruses. The test indicated that dengue 2 was endemic on Curaçao but not on Aruba, perhaps because of more effective vector control measures on Aruba. Neutralization tests performed with a samll number of sera suggest that dengue infections may have afforded some level of protection against yellow fever to a portion of the Curacao population.


Fetal deaths in the district of São Paulo, Brazil. A study has been made of fetal deaths registered in São, Paulo, Brazil, for the period 1 June 1968 through 31 May 1970. This article reports some of the findings of that study. Among other things, the findings revealed a higher incidence of male deaths than female deaths, high rates of fetal death associated with multiple pregnancy, a relatively low risk of stillbirth in certain maternal age groups, and an association between congenital anomalies and increasing maternal age.


Facts and figures on health in the Americas: a review of major trends. It is highly desirable, from time to time, to review important long-term trends in the health conditions of our Region. The account that follows provides a brief general overview of such trends as they have evolved over the last 20 years.


Community participation in health activities in an Amazon community of Brazil. This article describes community participation in a comprehensive eight-year health program at Porto Nacional, a town in Brazils Amazon region. The authors discuss various techniques employed to encourage community participation, indicate methods used to resolve low-key conflicts in a positive manner, describe the major contributions made by community participation in this program, and present a number of conclusions considered applicable to other communities in this part of Brazil.


Clinical evaluation of a sensory feedback device: the limb load monitor. Based on records of 81 patients who used the LLM, and on questionnaire answers and comments from clinicians, the following can be concluded: 1. The LLM can be operated easily after a minimum of training. It does not break down with extended clinical use when handled properly. 2. The LLM manual provides sufficient information for proper operation and clinical use of the device. 3. The number of patients in a clinic who can benefit from LLM training can be predicted, if consideration is given to the type of facility and the size of the patient population and physical therapy staff. 4. The largest diagnostic group of patients who can benefit from LLM therapy are lower-limb amputees, followed by hemiplegic and orthopedic patients. 5. The general selection criteria outlined initially proved sufficient. A patient who is selected properly can be expected to respond to the feedback signal (i.e., make a weight-bearing adjustment) within the first or second session.


Imaging: radioisotope imaging of bone.

Imaging: radioisotope imaging of bone. Isotope bone scanning is here to stay: it is noninvasive, easy to perform, and economical (6 pounds per scan). The low radiation dose delivered to patients (0.03 rad/mCi to the skeleton) and the high sensitivity (less than 4 per cent of overall false positives) underline the value of this test as a screening procedure. When included in the patient's management protocol it reduces bed-occupancy time, changes the therapeutic approach to several illnesses, and substantiates general hopes that early diagnosis is the basis for progress in the treatment of benign or malignant disease.


Corticosteroid involvement in the changes in noradrenergic responsiveness of tissues from rats made hypertensive by short-term isolation. 1 The responses to noradrenaline and to noradrenergic nerve stimulation of spontaneously beating right atria, electrically driven left atria and vasa deferentia taken from rats made hypertensive by short-term isolation have been compared with the responses of tissues from normotensive, group-housed animals.2 Adrenocortical activity of isolated animals was assessed by plasma corticosterone determinations and measurement of adrenal weights.3 The hearts of the isolated animals were weighed and the myocardial contents of water, sodium, potassium and calcium were measured.4 Spontaneously beating right atria from isolated animals showed a lower resting rate, no difference in the response to nerve stimulation but a greater sensitivity to noradrenaline compared to atria from group-housed animals.5 Vasa deferentia from isolated animals showed a decreased maximal response to noradrenaline, but no change in noradrenaline sensitivity or in the response to transmural stimulation.6 There were indications of hyperactivity of the adrenals throughout a 5 week period of isolation, manifest as elevated plasma corticosteroid levels and increased adrenal weights.7 Myocardial levels of sodium and calcium were elevated at the same time as the tissue level of potassium was reduced, but heart weights did not significantly change.8 It is possible that adrenal steroid action caused the changes in tissue ionic balance. These ionic disturbances may have been responsible for some of the changes in tissue sensitivity found in the isolated hypertensive animals.


Evidence for purinergic innervation of the anococcygeus muscle. 1 Fluorescence histochemical localization of quinacrine (which binds to adenosine 5'-triphosphate (ATP)) revealed nerve fibres running singly and in bundles in both rat and rabbit anococcygeus muscle. Single neurone cell bodies and ganglia containing between 2 and 50 cells were also observed.2 Catecholamine fluorescence studies revealed a dense adrenergic ground plexus, but no adrenergic ganglion cells were detected. No acetylcholinesterase-positive nerve fibres or ganglion cells were seen in the rat.3 When the tone was raised with guanethidine, a relaxation in response to field stimulation was revealed, which was unaffected by atropine but blocked by tetrodotoxin.4 Release of ATP increased 3 to 6 times above background during stimulation of these non-adrenergic, non-cholinergic, inhibitory nerves.5 Neither quinacrine staining nor the release of ATP during inhibitory nerve stimulation was affected by 6-hydroxydopamine treatment, which abolished catecholamine fluorescence.6 Exogenous ATP produced relaxation in high tone preparations of the rabbit anococcygeus muscle. ATP produced either contraction or a small relaxation followed by a contraction of the rat anococcygeus muscle, but treatment with low concentrations of the prostaglandin synthesis inhibitor indomethacin, converted the contraction to a relaxation.7 These data are consistent with the view that the anococcygeus muscle is innervated by purinergic inhibitory nerves.


Selective effects of morphine on the nociceptive responses of thalamic neurones in the rat. 1. The effects of intravenous morphine on the firing of single sensory neurones in the thalamus of the anaesthetized rat are described. 2. Low doses (0.38 to 2.00 mg/kg) of morphine depressed the excitation of nucleus lateralis neurones produced by natural noxious stimuli but were without effect on spontaneous activity. The excitation of some of these neurones by iontophoretically applied acetylcholine or glutamate was also depressed by morphine. These effects were reversed by intravenous (0.25 to 1.17 mg/kg) but not iontophoretically applied (50 to 200 nA) naloxone. 3. Similar or higher doses of morphine (0.58 to 5.07 mg/kg) did not prevent the excitation of ventrobasal thalamic neurones by non-noxious stimuli. 4. The possibility of a direct action of intravenous morphine in the thalamus is discussed.


Pharmacology of the adrenoceptors and cholinoceptors of the BC3H1 nonfusing muscle cell line. 1. We have studied the action of different transmitters on the transmembrane 42K or 86Rb efflux from tissue cultures of the BC3H1 muscle cell line. 2. The effect of catecholamines and carbachol (CCh) on the isotope efflux rate was measured by addition of the drugs at different times during the washout. 3. Noradrenaline (NA), phenylephrine (Phe), isoprenaline (Iso) and CCh increased 42K and 86Rb efflux rate in a dose-dependent manner. 4. The action of NA seems to be due exclusively to the stimulation of alpha-receptors, since its effect was blocked by phentolamine but not by propranolol. The effects of Iso on the 86Rb efflux were inhibited by propranolol. The beta-receptors in the BC3H1 cells seem to be the beta2-type since they are stimulated by Iso and insensitive to NA. 5. The effect of CCh was blocked (+)-tubocurarine but not by atropine. This result confirms the presence of nicotinic receptors in BC3H1 cells.


Adrenal origin of plasma catecholamines after decapitation: a study in normal and diabetic rats. The concentrations of catecholamines and the activities of dopamine-beta-hydroxylase were measured in blood obtained from decapitated diabetic and aged-matched control rats. The activity of dopamine-beta-hydroxylase in blood from diabetic rats was much greater (5 fold) than that seen for control rats. For both diabetic and control rats, decapitation was accompanied by an increase in levels of adrenaline and noradrenaline with no change in the activity of plasma dopamine-beta-hydroxylase. The results are consistent with a predominantly adrenal origin of catecholamines and extra-adrenal origin of dopamine-beta-hydroxylase. The high activity of dopamine-beta-hydroxylase in diabetes indicates either an increased activity of the sympathetic nervous system or changes in dopamine-beta-hydroxylase turnover.


Prevention by guanethidine analogues of output of noradrenaline induced by sodium reduction in rabbit ventricular slices. 1 The prevention by guanethidine and related agents of the output of noradrenaline induced by low sodium was investigated in rabbit ventricular slices. When external NaCl was reduced, the output of noradrenaline into the medium collected at 30 min intervals, increased and the endogenous levels decreased. These changes induced by replacing sodium with sucrose or choline were not affected either by the omission of calcium and addition of 0.5 mM ethylene glycol-bis(aminoethylether)N,N,N',N' tetra-acetic acid (EGTA) or by an increase in the calcium concentration to 10 mM 30 min before sodium deprivation.2 Guanethidine 4 x 10(-6) and 4 x 10(-5) M and 4-7-exo-methylene-hexahydroisoindoline-ethyl guanidine (No. 865-123) 4 x 10(-5) to 8 x 10(-4) M inhibited, in a dose-dependent manner, increases in output of noradrenaline induced by reduction of sodium to 18 mM, while guanethidine 8 x 10(-5) M and high doses of bretylium produced no inhibition: the latter two released noradrenaline.3 The inhibitory actions of guanethidine 4 x 10(-5) M and No. 865-123 4 x 10(-4) M were prevented by tetracaine 3.3 x 10(-4) M, which per se did not modify the output of noradrenaline induced by 18 mM sodium.4 Accumulation of guanethidine and No. 865-123 in ventricular slices was greater than that noted in striated muscle slices and was dose-, time- and temperature-dependent. Tetracaine 3.3 x 10(-4) M did not prevent the accumulation of guanethidine 4 x 10(-5) M and No. 865-123 1.1 x 10(-6) to 4 x 10(-4) M.5 The guanidine derivatives appear to increase the permeability of adrenergic nerve endings to sodium ions.


The development of tolerance to ketamine in rats and the significance of hepatic metabolism. 1. A decrease in sleeping time in rats pretreated with ten daily doses of ketamine compared to controls is shown. 2. This decrease in sleeping time is associated with a more rapid decrease in circulating and brain levels of ketamine and its N-demethylated metabolite and higher levels of the subsequent oxidation metabolite in the pretreated animals. 3. Metabolism of ketamine to its N-demethylated metabolite by liver homogenates in vitro was more rapid when the livers were obtained from ketamine pretreated rats. 4. Microsomal preparations from rat liver were capable of metabolizing ketamine to its N-demethylated metabolite and this metabolite to the subsequent oxidation metabolite in vitro. The Vmax and Km for the first reaction calculated from loss of substrate were 433 mol mg-1 protein h-1 and 0.133 mM respectively and 199 nmol mg-1 protein h-1 and 0.121 mM for the second reaction. 5. The results indicate that tolerance to ketamine in rats is associated with increased hepatic metabolism which can also be demonstrated in vitro in liver homogenates.


A comparison of drug-induced responses on rat tracheal, bronchial and lung strip in vitro preparations. 1. A preparation of rat trachea and a new preparation of rat bronchi are described. Both preparations are fluid-filled and the intraluminal pressure is monitored. 2. A preparation of rat peripheral airways, the lung strip, is described. The preparation consists of a thin strip of lung parenchyma which is superfused, and contractions monitored isotonically. 3. The rat trachea and bronchi have no intrinsic tone but increases in pressure are elicited in response to methacholine. The preparations relax in response to isoprenaline and aminophylline in the presence of a methacholine-induced contraction. Both preparations respond weakly and show tachyphylaxis to 5-hydroxytryptamine (5HT). 4. The lung strip contracts with equal magnitude to methacholine and 5-HT. It exhibits intrinsic tone which is inhibited by indomethacin and relaxed by isoprenaline.


The postnatal development of adrenoceptor responses to agonists and electrical stimulation in rat isolated atria. 1. Isolated right and left atria from rats of ages ranging from newborn to adult were used to measure chronotropic and inotropic responses to noradrenaline, isoprenaline, tyramine, and electrical stimulation of intramural nerves. 2. Right atria from newborn animals showed increases in rate with noradrenaline, isoprenaline, and tyramine which did not differ significantly from those of atria from adults. The ED50 values for the chronotropic actions of noradrenaline and isoprenaline were not significantly different at any age from the values in adult preparations. 3. Paced left atria from newborn rats showed well developed positive inotropic responses to noradrenaline and isoprenaline. Newborn left atria (and those from 1 and 2 week old animals) were supersensitive to noradrenaline but not to isoprenaline. 4. Left atria from newborn animals showed very small inotropic responses to both tyramine and field stimulation of intramural nerves. These responses developed progressively with age over the first three weeks of life. The results are discussed with respect to the development of cardiac beta-adrenoceptors and of cardiac sympathetic innervation.


Anti-depressant action of caesium chloride and its modification of chlorpromazine toxicity in mice. 1. Adult male mice were treated with caesium chloride (1.0 mEq/kg, i.p.) once daily for 54 consecutive days before administration of a single dose or reserpine (2.0 mg/kg) or (+)-amphetamine (1.0 mg/kg). Pretreatment with caesium chloride resulted in potentiation of amphetamine-produced enhancement of motility and in antagonism of reserpine-induced behavioural depression in mice as measured by a locomotor activity test, compared to the respective controls. 2. Chronic administration of caesium chloride (1.0 mEq/kg daily) with gradual dose build-up of chlorpromazine (up to 50 mg kg-1 day-1) counteracted chlorpromazine-produced mortality in mice. 3. The results suggest an antidepressant property of Cs+ and the combined treatment of caesium chloride with chlorpromazine might have a clinical application, i.e. in the management of chlorpromazine-induced adverse reaction.


Enhancement of a nociceptive reaction by opioid antagonists in mice. 1. The opioid antagonists, naloxone, GPA 2163, levallorphan and Mr-2266 reduced the latency of the jumping reaction of mice in the hot plate test. The (+)-isomers of levallorphan and Mr-2266 which are devoid of antagonistic activity did not increase this latency. 2. In the same nociceptive reaction test, the enhancing effect of naloxone progressed in a dose-range similar to that required for the antagonism by naloxone of the depressive action of morphine. 3. The facilitatory effect of naloxone was not blocked by the previous administration of morphine or etorphine but it was prevented by pretreatment with a high dose of buprenorphine. 4. The antagonism by naloxone of morphine and of buprenorphine did not follow the same pattern. 5. The factors which are or may be involved in the efficacy of naloxone in enhancing nociceptive reactions are discussed. 6. The enhancing effect of naloxone may be due to an antagonism of endogenous ligands for the opiate receptor. If so, these ligands would be involved in reaction to but not in perception of nociceptive stimuli which need not be harmful ones.


A new bioassay for glucagon.

A new bioassay for glucagon. 1 The relaxant action of glucagon has been studied in strips of rabbit renal arteries partially contracted by a low concentration (1 ng/ml) of noradrenaline.2 The preparation was relaxed in a dose-dependent manner by concentrations of glucagon varying between 25 ng/ml and 420 ng/ml.3 The relaxant effect of glucagon (0.1 mug/ml approximately ED(60)) on this preparation was not affected by propranolol (5.0 mug/ml), cimetidine (10 mug/ml), diphenhydramine (10 mug/ml), indomethacin (5.0 mug/ml), phentolamine (1.2 mug/ml), atropine (10 mug/ml) and 8-Leu-AT(II) (1.0 mug/ml) but was slightly potentiated by Des-Arg(9) Leu-OMe(8)-Bk (25 mug/ml) and indomethacin (50 mug/ml).4 The dose-response curve to glucagon remained parallel in the presence of papaverine (2.5 mug/ml) but was shifted to the left by a factor of 2.5 to 2.8. Theophylline (250 mug/ml) also potentiated the vascular relaxation induced by glucagon.5 Insulin (10 mug/ml) did not influence the relaxant effect of glucagon.6 The removal of the N-terminal amino acid (His) of glucagon reduced by 89% the biological activity of this fragment on the vascular preparation. The removal of the C-terminal amino acids Met-27, Asn-28 and Thr-29 of glucagon resulted in a fragment which was inactive either as an agonist or as an antagonist when tested at concentrations as high as 925 ng/ml.7 It is concluded that the relaxation of partially contracted strips of rabbit renal arteries by glucagon constitutes a simple, sensitive, relatively specific and reliable bioassay which may be useful for the determination of glucagon in biological materials and for structure-activity relationship studies with this hormone.


A study of thyroid function in psychiatric in-patients. The prevalence of abnormal serum total thyroxine (T4) and triiodothyronine (T3) concentrations were determined in 1,206 in-patients in two associated psychiatric hospitals. The biochemical pattern of primary hypothyroidism occurred in five females and one male (prevalence 0.5 per cent), but in only one patient was the diagnosis clinically obvious. Eight patients (all female) were clinically hyperthyroid (prevalence 0.7 per cent), of whom six were previously undiagnosed. There was no evidence that phenothiazines or benzodiazepine therapy had any significant effect on thyroid hormone levels. The small differences in thyroid hormone levels between psychiatric diagnostic groups could be explained by differences in age distribution.


Thyrotoxicosis and the course of manic-depressive illness. The effect of thyrotoxicosis upon the recurrence of manic-depressive psychoses has been studied by the use of a routine follow-up system. In this system 267 patients had three or more affective illnesses. Five of these patients had eight well-documented episodes of thyrotoxicosis. Only three of these eight episodes coincided with an affective illness, and in each case an alternative explanation for the association was available. These findings suggest that thyrotoxicosis has little effect upon the occurrence of a manic-depressive episode.


Accidents in a psychiatric hospital.

Accidents in a psychiatric hospital. In a six-month study of psychiatric hospital in-patients, it was found that accidents more often occurred among females and among patients on psychogeriatric wards. Falls were the most common form of accident. Accidents resulting from the aggressive behaviour of other patients usually occurred on long-stay and rehabilitation wards, with middle-aged patients the victims.


Matiruku, a Fijian madness: an initial assessment. In Fijian, matiruku means literally 'low tide in the morning' and figuratively somebody periodically insane. In this study, the conceptual basis of matiruku was examined by means of a questionnaire completed by 24 Fijians which explored its occurrence, aetiology and precipitation, phenomenology, management and prognosis. It was concluded that matiruku corresponds to hypomania, which may have special features in Fiji: short duration, frequent recurrence and an intensification of symptoms in the morning.


Brain specific benzodiazepine receptors. Brain membranes from rat and human contain a single class of brain specific binding sites for pharmacologically and clinically active benzodiazepines. There is good correlation between the pharmacological effects of benzodiazepines and the affinity for the 3H-diazepam binding site. Benzodiazepine binding sites are not present on glial cells. Selective neuronal degeneration experiments in rats indicate a neuronal localization. 3H-Flunitrazepam is a very suitable ligand for affinity binding and it binds to the same class of binding sites as 3H-diazepam. Our results indicate that the in vitro 3H-diazepam and 3H-flunitrazepam binding sites are the receptors which in vivo mediate various pharmacological and clinical effects of benzodiazepines.


Delinquency and the development of moral reasoning. A sample of 34 incarcerated male delinquents aged 16-17 and a matched group of controls were compared on self-report measures of delinquency, on Rest's (1975) Defining Issues Test (DIT) of moral reasoning, and on measures of logical operational ability. The mean levels of self-reported delinquency of the incarcerated group were substantially higher than those of the controls. There was no significant difference between the groups in logical operational ability but the mean P score (index of mature moral reasoning) was significantly higher in the control group. However, no relationship was found between moral reasoning and levels of self-reported delinquency. It was concluded that degree and seriousness of involvement of delinquency is unrelated to immaturity of moral reasoning and that the utility of the cognitive developmental approach to moral socialization may therefore be more restricted than has previously been claimed.


Necker cube reversals, arousal and psychopathy. Necker cube reversals were studied in a group of 24 arrested men in three experimental sessions; two weeks, one week and immediately before trial. The first session was assumed to represent a moderate laboratory stress due to the novelty of the situation, and the last session a real-life stress associated with anticipation of appearing in court. Both were superimposed on the sustained real-life stress of being in jail. There were no stress-related changes between the three sessions in the rate of apparent change (RAC) of the Necker cube. The intra-individual stability of RAC was extremely high. There were significant positive correlations between RAC in all sessions, and a psychopathy-related inventory scale, the Gough delinquency scale.


The craving factor in the treatment of smoking. A review of previous studies suggests that many of the consistent results obtained may reflect individual differences in smoking behaviour. It was felt that Tomkins' (1966) distinction between craving and non-craving smokers would be particularly relevant to this. The present study investigates the effects of such individual differences in smoking behaviour within a self-control treatment programme. Thirty-four smokers were assigned to three groups: two self-control treatment groups and an attention-monitoring control group. The treatment groups differed in that group II concentrated on the positive aspects of not smoking, whereas group III used a wide range of techniques. Treatment effects were not significant but a critical factor in abstinence, drop-out and percentage reduction during the study was craving/non-craving status. The results indicate that two separate populations of smokers exist who seem to have different responses to treatment. This, it is argued, has blurred analysis of results in previous studies. The two types of smoker may require separate treatment considerations, both in therapy and in long-term management.


Spurious and actual improvement in the treatment of preoccupying thoughts by thought-stopping. Two clients troubled by preoccupying thoughts were treated by a version of thought-stopping described by Wolpe (1969) which has been infrequently reported so far. The frequency of spontaneous intrusive thoughts as they occurred within sessions was found to be a useful measure of clinical outcome, but it is suggested that careful control and definition of variations in procedure is necessary in order to eliminate spurious results. Treatment was found to produce an improvement which was maintained at follow-up.


The analysis of interactions in experiments on the specificity of schizophrenic thought disorder: a reply to Phillips. Phillips (1977) has criticized the investigation of statistical interactions in a series of related papers concerned with the specificity hypothesis of schizophrenic thought disorder. In a discussion of these criticisms, some are accepted and some rejected. However, when the relevant data are reanalysed by a correct method for the investigation of nominated interactions, the specificity hypothesis is broadly supported. A new finding to emerge from the reanalysis is that, in two experiments where level of 'difficulty' of constructs was controlled, the specificity effect appears much reduced or non-existent when intensity scores are employed while remaining intact for consistency scores.


Intrarenal reflux--papillary morphology and pressure relationships in children's necropsy kidneys. A radiological study of the necropsy kidneys of 100 children was made. Morphologically it was shown that compound or fixed papillae predominate in the upper group of calyces and to a lesser degree in the lower group, whilst simple papillae occurred in the middle group. Pressure studies showed that intrarenal reflux occurred in compound papillae at lower pressure than in simple papillae and that lower pressures were required to produce intrarenal reflux in the first year of life.


Radiographic findings of Ewing's sarcoma of the jaws. The radiographic findings in eight cases of Ewing's sarcoma of the jaws are analysed in detail. Similar findings to those in peripheral skeletal involvement were demonstrated including: (a) permeative bone destruction, (b) periosteal reaction, and (c) extraosseous soft tissue mass. Specific to the jaws is the occurrence of dental displacement without destruction. The differential diagnosis of Ewing's sarcoma of the jaws is discussed in detail and illustrated.


Post-thoracotomy lung herniation.

Post-thoracotomy lung herniation. Two cases of lung herniation complicating thoracotomy are presented. The classification and radiographic findings of lung hernia are reviewed.


Retained surgical swabs: possible causes for errors in x-ray detection and an atlas to assist recognition. A swab or pack left in a patient may not be recognised on a radiograph. This will usually be due to poor observation, but errors may result from unfamiliarity with the pattern of the markers. In addition, some markers may be difficult to detect, though this usually applies only to swabs which are very small or to those produced by some continental manufacturers. It should also be realised that, in a very few hospitals, swabs which do not have an opaque marker may occasionally be used in theatre. All the X-ray detectable swabs provided by the major suppliers in the U.K. are demonstrated.


A heavy particle comparative study. Part I: depth-dose distributions. The results of a comparative study of heavy particles of interest in radiotherapy, with peaks spread over a depth of 10 cm, are reported in four parts. The introduction to this study and the depth-dose distributions of the particles, (n, pi-, p, He, C, Ne, and Ar ions) are reported herein. The results indicate that protons give the best localization of dose. The degree of localization of dose with heavy ions is reduced with increasing charge on the ion. For ranges less than 15cm, heavier ions such as neon and argon still have favourable dose localization; however, for ranges in excess of 15 cm, heavy ions such as argon are unfavourable but superior to fast neutrons because penetration can be controlled by modulation of energy or range.


A heavy particle comparative study. Part II: cell survival versus depth. Cell-survival measurements with depth of penetration were made for a series of incident doses of proton, helium, carbon, neon, argon, negative pion, neutron, and 60Co photon beams. Cultured human cells (T1) suspended in a gel-containing medium were used, and the measurements were found to be very useful in facilitating the design of ridge filters to produce iso-effects in the region of interest. Heavy charged particle beams (proton, helium, carbon, neon, and negative pion) were found to produce similar cell killing with depth of penetration. Because of saturation effects at higher LET, argon ions were less effective in killing aerated cells at depth, compared with other heavy charged-particle beams. Cell killing at depth in the region of interest, compared with that at the entrance, was not significantly different for single-field exposures when the Bragg peaks were broadened to cover a width of 10 cm. However, when two opposed fields with overlapping peaks were used, a large enhancement in killing was obtained in the peak region.


A heavy particle comparative study. Part III: OER and RBE. The results of a comparative study of heavy particles of interest in radiotherapy are reported in four parts. In this Part III, cell-survival measurements under aerobic and hypoxic conditions were made for various heavy particle beams. For heavy charged-particle beams, the measurements were made at the beam entrance (plateau), peak centre (10 cm wide peaks), and distal peak (1 cm from dose fall-off). Chinese hamster cells (V79) were used. Metabolic depletion was used to obtain hypoxia. The results indicate that the differences in RBE between the entrance region and peak are not very large when the Bragg peaks are broadened to 10 cm. The RBE for argon ions remains the same at the entrance and peak centre, and the RBE at the distal side of the Bragg peak is significantly reduced compared to the peak centre and entrance region because of saturation effects at high LET. The OER for protons is not significantly different from that for X rays. The OER for helium ions, carbon ions, and negative pions is larger, for neon ions is similar, and for argon ions is smaller when compared with fast neutrons. The OER values for heavy ions are higher than expected and could be due to a large delta-ray penumbra associated with the energy deposited by energetic heavy ions. The oxygen effect may depend upon energy deposition over distances of the order of nanometers.


A heavy particle comparative study. Part IV: acute and late reactions. The results of a comparative study of heavy particles of interest in radiotherapy are reported in four parts. In this Part IV, early skin reactions and late reactions (foot deformity) in mice for various heavy particles are reported. For heavy charged particles, the exposures were made at the entrance region (plateau) and centre of the peak (10 cm wide peaks). For 60Co gamma rays and fast neutrons (50 MeV D leads to Be), the exposures were made at the peak of the depth-dose curve. The time-course of development of skin reaction and subsequent healing after exposure to heavy ions or 60Co gamma rays were remarkably similar, suggesting that skin damage and subsequent epithelial repopulation after exposure to heavy ions are not different from 60Co gamma rays. When the Bragg peaks were broadened to 10 cm, the RBE at the peak, compared with the entrance region, was significantly higher for carbon ions but nearly the same or even lower for neon and argon ions because of saturation effects at high LET. The RBE for fast neutrons was comparable to that at the peak for carbon ions. The correlation between early skin reaction and foot deformity remained the same for all particles.


The B-scan ultrasonic appearances of gas in the biliary tree. Gas in the biliary tree has a striking but not unique ultrasonic appearance consisting of acoustic shadows trailing behind well-defined discrete high amplitude echoes deep within the liver parenchyma, and may be mimicked by intrahepatic gall stones and calcified tumours and granulomas. It interferes with assessment of liver structure, and renders ultrasound B-scan unreliable for the detection of liver metastases. Computed tomography remains unaffected by biliary gas.


Topical noxythiolin in colonic healing.

Topical noxythiolin in colonic healing. Rats were subjected to division and anastomosis of the colon just proximal to the rectum to study the healing of colonic anastomoses. The effect of noxythiolin irrigation of the divided colon before and after anastomosis was investigated and compared with controls. Healing was assessed using five variables--macroscopic and microscopic inspection, bursting pressure and tensile strength estimations and angiography for new vessel formation. The study shows that noxythiolin irrigation of the colon in the rat significantly increases the chance of a sound anastomosis without interfering with healing. Furthermore, it inhibits the formation of adhesions.


Excluded loop syndrome: a complication of jejuno-ileal bypass for obesity. Excluded loop syndrome may develop in patients who undergo jejuno-ileal bypass surgery with the excluded small intestine drained via an ileosigmoidostomy. A unique case of a morbidly obese male who underwent the procedure while on methadone maintenance therapy is presented. The major factor in the development of this disorder appears to be the high intraluminal pressures within the sigmoid colon which prevent adequate egress from the excluded loop. Narcotic medications tend to induce or intensify the syndrome.


Early results with human umbilical cord vein allografts for haemodialysis. Six patients requiring intermittent haemodialysis for chronic renal failure underwent construction of an arteriovenous fistula using modified human umbilical cord vein allografts. Three grafts soon showed degenerative changes and were removed--2 thrombosed and 1 became infected. Satisfactory haemodialysis was achieved with the remaining 3 grafts. Two grafts are currently patent at 9.5 and 11 months respectively, while another graft became aneurysmal after 8 months, requiring its removal.


Post-amputation pneumatic walking aid.

Post-amputation pneumatic walking aid. A pneumatic walking training aid is described that has been developed by the Biomechanical Research and Development Unit, Roehampton, from the original design by Little. The new design has been used in the management of 87 amputations, including 44 patients over the age of 70. Ninety-four per cent of these patients were rehabilitated to walking independently on a pylon or prosthesis.


Popliteal artery entrapment syndrome: a case report. A rare case of bilateral popliteal artery entrapment syndrome is reported. Pathological changes of the occluded lesion in this anomaly were investigated in 8 other cases. Abnormal longitudinal muscle in the media was noted in all. Development of these muscle bundles was considered to be due to chronic trauma inflicted by pressure on the arterial wall. Its significance is emphasized to assist in differentiation from other chronic arterial occlusive disease.


The fibrinogen uptake test after hip surgery. The fibrinogen uptake test has been used to detect deep vein thrombosis after total hip replacement in 90 patients. The upper third of the thigh in each leg was ignored and peripheral leg counting carried out distal to this. The results were directly compared with the findings of venography in the 170 legs of the 90 patients. There was a high false positive rate (30 per cent) with the fibrinogen uptake test which was associated with the presence of the knee joint effusion or varicose veins, but not with the site of operation. There was a low false negative rate (less than 5 per cent), and the fibrinogen uptake test, used in this way, may fail to detect a percentage of small thrombi in the wound area that are probably produced by the local trauma of operation. It is considered that the fibrinogen uptake test has a clinical use as a screening test for deep vein thrombosis after hip replacement, but venography is required in the interests of accuracy.


Acute abdominal complications of systemic lupus erythematosus. Four patients with acute abdominal complications of systemic lupus erythematosus requiring laparotomy are presented. The complications consisted of intestinal ischaemia, without perforation, in 3 patients and omental infarction in the fourth. In 2 patients the abdominal emergency was the first manifestation of the collagen disease. Tissue removed from 3 patients showed a marked vasculitis on histological examination. The pathogenesis and management of acute abdominal complications of systemic lupus erythematosus are discussed and the literature reviewed.


Spontaneous rupture of the oesophagus and massive pneumoperitoneum. A case of spontaneous rupture of the abdominal oesophagus is described. The presentation, after an interval of 4 weeks from the onset of symptons, was unusual with massive pneumoperitoneum without peritonitis.


The relationship between the rate of gastric emptying and the dumping syndrome. Following an oral hypertonic glucose challenge, gastric emptying and changes in plasma volume were measured in 15 subjects before and in 36 subjects after a truncal or selective vagotomy with a drainage procedure. The symptoms experienced during the test were noted, and the postoperative patients divided into two groups, (a) 20 patients who experienced dumping symptoms during the test and (b) 16 patients who did not. Gastric emptying was significantly faster and the fall in plasma volume significantly greater in those patients who experienced symptoms after the ingestion of hypertonic glucose than in those who did not, clearly demonstrating that the dumping syndrome is associated with an increased rate of gastric emptying. In addition, there was a significant positive correlation between the rate of gastric emptying and the fall in plasma volume.


Diets and stoma function.

Diets and stoma function. Fifty ileostomy and 50 colostomy patients were questioned as to which foods upset their stoma function. Most patients had no problem in finding a suitable diet and 70 per cent would eat any food on occasions, although half the patients found that side effects with particular foods were a nuisance. Only a small range of foodstuffs seemed to produce symptoms in a significant proportion of patients. We feel that no particular foodstuff should be eliminated from a diet without an adequate trial as most patients are able to eat entirely normally.


The prognostic and therapeutic implications of the positive radionuclide bone scan in clinically early breast cancer. Seventy-five women with clinical stage I or stage II carcinoma of the breast have had radionuclide bone scans at the time of presentation and at 6-monthly intervals during a mean follow-up period of 39 months. Patients with evidence of metastases on bone scan, either at the time of presentation or during follow-up, had significantly higher mortality and morbidity rates than those with persistently negative scans. Whatever the clinical stage, breast cancer patients with a positive bone scan have a very poor short term prognosis and local therapy to the breast is inadequate. A plan is outlined which incorporates the patient's bone scan status into the decision to introduce endocrine therapy or chemotherapy.


The plasma clearance of fructose and glucose during and after surgical operation. Fasting blood glucose is elevated and the rate of disappearance of a glucose load is reduced after major surgery. Resistance to insulin is considered to play a part in post-traumatic glucose intolerance. Fructose metabolism is partly independent of insulin. Glucose and fructose clearance were compared in two groups of 6 matched male patients with normal glucose tolerance who were studied before and after major vascular surgical operations of the same severity. Fructose or glucose (25 g) was given intravenously over a 2-min period before, during and at intervals for 8 days after surgery. The rate of clearance of fructose increased significantly during operation (P less than 0.01), but returned to the preoperative level by the first postoperative day. Glucose clearance, in contrast, was reduced during and throughout the 8 days of the study. The fructose load produced a brisk insulin response before operation which was diminished and delayed during surgery. These findings suggest that administered fructose may be removed more rapidly than glucose during and immediately after surgical operation.


Liver function and lactate metabolism in the ill surgical patient. Liver function and lactate metabolism were investigated in non-shocked, severely ill surgical patients. Fasting venous blood lactate concentration was increased and plasma liver function tests were abnormal in ill patients compared with controls. Ill patients were glucose-intolerant and blood lactate changes following intravenous glucose infusion were similar in both ill and control patients. Blood lactate half-life was increased in ill patients following a sodium L-lactate infusion, suggesting that the increased fasting lactate concentration may have been due to decreased hepatic removal rather than to increased peripheral production of lactate.


The effect of elective surgery on 3-methylhistidine excretion. Elective surgical operation in normally nourished patients is associated with an increase of up to 40 per cent in the urinary excretion of 3-methylhistidine during the first three postoperative days. This increase was statistically significant (P less than 0.01) on the second and third postoperative days. This probably represents a minor degree of increased muscle proteolysis, principally due to the operative trauma. The possible effect of postoperative starvation requires further elucidation.


Treatment of Raynaud's phenomenon by fibrinolytic enhancement. Twenty patients with advanced Raynaud's phenomenon, in 14 of whom it was secondary to scleroderma, were treated with stanozolol, an anabolic steroid that enhances natural fibrinolysis. All showed an increase in hand blood flow and a reduction in symptoms during treatment. This response may have been caused by the lysis of fibrin deposited in the digital arteries and the reduction of plasma viscosity. Stanozolol is a useful addition to the treatment of patients with advanced Raynaud's phenomenon who have trophic changes.


Indian childhood cirrhosis: an inherited disorder of tryptophan metabolism? Urine samples from members of 29 families of patients with Indian childhood cirrhosis (ICC) and nine families with related disorders gave positive reactions when tested with ferric chloride. Column chromatography showed that this was due to the presence of abnormally large amounts of tryptophan metabolites, notably 3-hydroxyanthranilic acid. Affected pedigrees had a significantly greater prevalence of peptic ulcer, adult cirrhosis, diabetes mellitus, migraine, and Parkinsonism than a control population. ICC may result from an inborn error of tryptophan metabolism in susceptible ethnic groups.