A modified sternal retractor.

A modified sternal retractor. A modification of the Favaloro sternal retractor is described that allows a singel person to operate the apparatus when elevating the sternal plate. The new retractor is also easier on the sternum because of its blunter teeth.


Survival following free rupture of left ventricular aneurysm: report of a case. A 50-year-old man sustained free rupture of the left ventricle four weeks following a massive anterior myocardial infarction. The rupture occurred at the junction between a bulging left ventricular aneurysm that was not yet fibrotic and normal myocardium without evidence of fresh myocardial infarction. Accurate preoperative diagnosis aided by echocardiography and right heart catheterization made possible a planned surgical approach. Postoperative support with intraaortic balloon pumping appeared to be beneficial in maintaining statisfactory cardiac function until an adequate stroke volume could be reestablished, presumably by an increase in left ventricular volume.


Aneurysm of the main pulmonary artery: long-term survival after aneurysmorrhaphy and closure of a ventricular septal defect. Pulmonary artery aneurysm (PAA) usually carries an ominous prognosis due to the associated pulmonary hypertension. Six years ago a patient with a PAA secondary to cystic medial necrosis and pulmonary hypertension due to a ventricular septal defect (VSD) was treated by aneurysmorrhaphy and closure of the VSD. Although the patient had early postoperative cardiac failure, his cardiopulmonary status stabilized, and he has done well without recurrence of his aneurysm or cardiac failure. This report summarizes the patient's clinical course, operative treatment, and long-term follow-up.


Binocular fixation pattern.

Binocular fixation pattern. The binocular fixation pattern (BFP) is a convenient clinical test that may be used to diagnose strabismic amblyopia in children who are too young to cooperate with conventional testing of visual acuity. A retrospective analysis of amblyopic and nonamblyopic patients with esotropia and exotropia demonstrates the effectiveness of the BFP in detecting strabismic amblyopia in children under 4 years of age. Amblyopic patients with either esotropia or exotropia reliably demonstrate strong grades of preference. Nonamblyopic patients with esotropia or exotropia usually demonstrate weak grades of fixation preference, with the important exception that most patients with small angles of esotropia have strong fixation preference even in the absence of amblyopia.


Carcinoembryonic antigen. Its role in the evaluation of intraocular malignant tumors. Plasma carcinoembryonic antigen (CEA) was studied in 60 patients with histologically confirmed intraocular neoplasms including 56 malignant melanomas of the uvea and four metastatic tumors to the choroid. While 45% of the patients with primary uveal melanomas, as well as 75% of the patients with metastatic disease demonstrated elevated plasma CEA levels, both patients who exhibited metastatic lesions of entodermal origin demonstrated plasma CEA values that clearly fell into a separate, highly elevated category, consistent with metastatic disease or pancreatic or colorectal carcinoma. Thus, in the patient seen with a nonpigmented choroidal mass that may represent either a choroidal hemangioma, amelanotic melanoma, or metastatic tumor, plasma CEA levels may be useful in the differential diagnosis. If the clinician suspects a metastatic tumor from an occult primary site, highly elevated CEA levels may indicate that the lesion is of entodermal origin.


The iris-plane (Copeland) pseudophakos.

The iris-plane (Copeland) pseudophakos. The iris-plane (Copeland) pseudophakos was evaluated in two 81-case surgical series. An early series consisted of the first 81 operations performed in the Miami community before a temporary moratorium on Oct 1, 1969. This series was compared with the first 81 operations performed after the moratorium was lifted on Oct 1, 1971. The follow-up period of those available for study was 63 months in the early series and 19 months in the later series. Objectivity was assured since all surgery was performed by one author (N.S.J.) and all examinations performed by the other author (L.R.D.). Visual acuity of 6/12 or better was obtained in approximately 80% of patients. The most frequent problems encountered were recurrent iritis and cystoid macular edema. The optic benefit was apparent in this elderly group of patients who avoided the optical problems of aphakia.


Fluorophotometry and the rate of aqueous flow in man. II. Primary open angle glaucoma. By fluorophotometry, the aqueous outflow rates of 38 eyes of 22 patients with definite or suspected primary open angle glaucoma, who were not receiving therapy, were determined. Although the values obtained do not differ from normal, the factors that modify or control the flow rate are different in normal and glaucomatous eyes. The flow rate decreases as the pressure increases in the glaucomatous group but not in the normal group. The flow rate increases with anterior chamber depth and decreases with age in the normal group but not in the glaucomatous group. The fluorescein decay constant is a measure of the movement of fluorescein from the cornea to the aqueous. This constant increases as the pressure increases in the glaucomatous group but not in the normal group.


The effect of the honeycomb on glare function. Patients with certain forms of cataract or corneal disease have diminished visual acuity in a brightly lit environment. This is due to increased light scattering, which causes increased glare sensitivity. In a series of experiments, a sequence of bottles containing a suspension of latex particles was used to simulate the effect of different degrees of cataract and corneal edema on visual acuity. It was shown that anodized honeycombs could substantially improve visual acuity through the latex-containing bottles. The mechanism of visual improvement was shown to be by reduction of glare and increase in contrast.


Cyclic esotropia developing after sttstrabismus surgery. Cyclic or alternate-day esotropia developed in a patient following strabismus surgery for intermittent exotropia, which resulted in a small overresponse or overcorrection. Surgery, aimed at the deviation on the esotropic days, resulted in binocularity and loss of the cyclic pattern.


Reversible unilateral lens opacities in a diabetic patient. Following one month of poor diabetic control, a 54-year-old patient presented with a unilateral posterior subcapsular cataract, consisting of numerous fine, feathery, streak-like opacities radiating from a dense, round, central, posterior, subcapsular plaque. Except for extensive pseudoexfoliation, the fellow lens was clear. After a subsequent week of strict diabetic control, the feathery streak-like opacities had almost disappeared. The findings are discussed in relation to the experimentally induced sugar cataract in which sugar alcohol accumulation and subsequent lens swelling result in a potentially reversible lens opacification.


Funduscopic appearance of papilledema with optic tract atrophy. In a child with a hypothalamic glioma, elevated intracranial pressure and retrograde optic tract atrophy produced distinctive patterns of papilledema and disc pallor in each eye. On the side of the tract lesion, the disc was swollen nasally and was pale temporally. In the contralateral fundus, the swollen optic disc was bisected horizontally by a pale atrophic band. These funduscopic signs exemplify a rare instance in neuro-ophthalmologic diagnosis wherein specific lateralizing and localizing information can be deduced solely from the appearance of papilledema.


Protozoan feeding and bacterial wall growth. Monod's model is often assumed to describe the kinetics of feeding of a protozoan population on a bacterial population in a chemostat. An earlier study (J. L. Jost et al., J. Bacteriol., 113, 84 (1973)) of the feeding of Tetrahymena pyriformis on either Escherichia coli or Azotobacter vinelandii found that this model correctly predicted the occurrence of sustained oscillations of population densities but made predictions of minimum bacterial population densities that were much smaller than those observed. The earlier study removed the discrepancy between the model and data by replacing Monod's model with a different model. It is shown in the present study that the discrepancy can be explained equally as well if Monod's model for the feed relation is retained and if, in addition, growth of bacteria on the chemostat walls is allowed for in the model equations.


Cooling rate effects in thermoluminescence dosimetry grade lithium flouride. Implications for practical dosimetry. A systematic investigation of the effects of cooling rates in the range of 10(-1) to 2 X 10(5) degrees C min-1 applied to TLD-700, LiF thermoluminescence dosemeters has shown that the 'transfer sensitivity' effect observed by Booth, Johnson and Attix (1972) is only of importance for cooling rates greater than 10(3) degrees C min-1. Although it is concluded that for practical dosimetry purposes the effect may be ignored it is not clear why Booth et al. observed such large changes and until this discrepancy is explained it is recommended that a low temperature pre-irradiation anneal should be used.


Observations on the combined effect of ultrasound and x-rays on the growth of the roots of Zea mays. The roots of Zea mays seedlings were exposed to ultrasonic radiations (1 MHz) of intensities in the range of 0-1-0-8 W cm-2 (pulsed or continuous modes) for times between 2 and 60 min, together with an X-ray dose of 775 rad which was given before, after or simultaneously with the ultrasound. These experiments have shown that ultrasound and X-rays seem to act independently of each other, suggesting that the mechanism of damage due to X-rays is different from that due to ultrasound. An increase in the X-ray effectiveness under the action of ultrasound, as reported by various authors who worked with different tissues, has not been found.


The andrenocortical homolog in the lake sturgeon, acipenser fulvescens rafinesque. The adrenocortical homolog in the chondrostean fish, Acipenser fulvescens, is confined within yellow corpuscles located at the dorsal junction of the two kidneys near the cardinal veins. The concentration and distribution of this tissue in chondrosteans appear to be a condition intermediate between that of cyclostomes and teleosts. The homology of this tissue to adrenocortical tissue of higher vertebrates is demonstrated in its delta5-3beta-hydroxysteroid dehydrogenase activity and the ultrastructure of the cells. The cells contain large lipid droplets and an abundance of smooth endoplasmic reticulum and mitochondria. The abundance of smooth endoplasmic reticulum, a large Golgi apparatus and an extensive elaboration of the plasma membrane suggest the high degree of steroidogenic activity of these cells. Apposed plasma membranes make contacts through the unique cell contacts described in the adrenocortical cells of mammals (Friend and Gilula, '72). The Golgi apparatus is described as a most conspicuous component of the cytoplasm and is presented as further evidence for the important involvement of this organelle in corticosteroidogenesis in vertebrates. These morphological observations are discussed in relation to the known secretory products of this tissue in the sturgeon, and it is suggested that there is a need for further examination of the corticosteroids produced by lower vertebrates.


A portable beam for mounting intensive care devices. A portable beam for accommodating many devices necessary to intensive care is described. It can be clamped to bedheads, trolley tops, working surfaces, or between intravenous stands and thus neatly converts an ordinary bed-space into an intensive care area.


Local anesthesia for suspension microlaryngoscopy. Despite the strong trend toward use of general anesthesia for laryngoscopy, local anesthesia retains inherent advantages from the standpoint of patient safety and maintenance of physiologic function of the larynx during endoscopy. Topical anesthesia produces incomplete sensory blockade and is unsatisfactory for suspension laryngoscopy. A method of infiltration anesthesia is described whereby profound anesthesia of the base of the tongue, valleculae, and larynx can be achieved to allow suspension laryngoscopy.


[Systemic candidiasis with localization in the brain. Anatomo-clinical study of 5 cases]. Central nervous system involvement in Candida septicaemia is rare and not more than four cases have been published in Brazil. Five new cases of systemic candidiasis with cerebral lesions are reported. All patients (four adults and a child) had serious underlying diseases and were submitted to heavy long-term antibiotic therapy with multiple drugs. Seizures in one case and neck stiffness in another were the only neurologic signs that could be attributed to candidiasis. In no case were the lesions severe enough to be considered an immediate cause of death. In three patients, no macroscopic changes were evident in the brain, but microabscesses and granulomata were observed on microscopical examination; another patient had two gross areas with necrotic and haemorrhagic appearance in the cerebral hemispheres; the child had only two microscopic granulomata. The aetiological agent was demonstrated by Grocott's methenamine silver technique in all cases. Involvement of organs other than the central nervous system could be demonstrated in three autopsies. Discussion is confined mainly to such aspects as the contributory factors in the pathogenesis of systemic candidiasis as well as the marked rise in the incidence of this condition in the past few decades. It is suggested that the frequence of monilial septicaemia in Brazil may be far more serious than apparent from the scarcity of reported cases.


[Acute paraplegia due to embolism from nucleus pulposus tissue (author's transl)]. Typical anterior spinal artery syndrome with initially severe pain and paraplegia with sensory disturbances occurred after a fall in a 36-year-old man with a history of lumbago. Multiple emboli of fibrocartilaginous material with nucleus pulposus cells were found in the foci of myelomalacia. The embolism of nucleus pulposus tissue originating from Schmorl's nodules was probably carried via the blood vessels of the neighbouring vertebral bodies with retrograde flow through the perispinal venous plexus into spinal cord veins and hence into the arteries of the spinal cord via veno-arterial anastomoses. A transitory increase in intra-abdominal pressure was probably the cause of the inversion of venous flow.


[Surgical treatment of ventricular aneurysm: an analysis of post-resection haemodynamic changes (author's transl)]. Of 500 patients with angiographically proven myocardial infarction 75 had a left ventricular aneurysm. 25 of them subsequently had resection of the aneurysm. Postoperative studies revealed marked improvement of symptoms. Pulmonary arterial pressure was significantly decreased at rest (from 28 to 20 mm Hg) and on exercise (from 58 to 35 mm Hg). There was a reduction in left ventricular end-diastolic volume (from 247 to 1.54 ml/1.73 m2) and a raised ejection fraction (from 36 to 59%). Good results were obtained especially in those patients who had congestive heart failure due to paradoxical systolic expansion of the ventricular wall and (or) secondary reversible damage in the remaining viable myocardium. Left ventricular aneurysms should be suspected after myocardial infarction when there is left ventricular failure and an increase in heart size.


Ultrastructure and cytochemistry of bone marrow granulocytes in culture. Leukocytes from human bone marrow, grown in clonal cell culture with methylcellulose medium, were characterized ultrastructurally and cytochemically, utilizing techniques for demonstrating peroxidase, acid phosphatase, dialyzed iron reactive mucosubstance, antimonate reactive cation and Concanavalin A surface receptors. Neutrophils and eosinophils were identified in culture specimens and in many respects resembled those seen in direct marrow specimens. Cultured neutrophils, however, did not develop secondary (specific) granules and the crystalloids of eosinophil granules appeared abnormal. The strong reaction of neutrophil primary granules with antimonate and dialyzed iron afforded differentiation from unreactive monocyte-macrophage granules and thus distinguished these cell types in culture. Basophils were observed in morphologic preparations and their granules stained most intensely for acid mucosubstance with the dialyzed iron method.


Confirmation of the human thymidine kinase locus, 17q21 leads to 17qter, by means of a man-mouse somatic cell hybrid, D98/AH-2 X LMTK-Cl-lD. A large metacentric marker chromosome, m20, in a line of human D98/AH-2 cells was identified by Q bands as being a translocation (1;17)(p36;q21). This was confirmed by means of somatic cell hybridization between D98/AH-2 and thymidine kinase (TK) deficient mouse cells. The hybrid clones by HAT selective system retained m20, indicating the presence of TK locus on this chromosome. The results also provide evidence that TK gene is located on the distal region of the breakpoint in 17q21 but not on 17q21 leads to 17pter.


[Epithelial invasion of the anterior chamber. Apropos of eight cases operated on using Maumenee's technic]. Eight cases of epithelial downgrowth have been operated on by Maumenee's technique. Two cases were considered entirely successful, using the stringent criteria of Maumenee. Four other cases were partly successful maintaining a visual acuity of 20/300-20/400 without any recurrence, and normal ocular pressure or glaucoma controlled by topical medication. The value of Maumenee's surgical technique in these cases is obvious if one wishes to save these patients' eyes and keep useful vision. The only change suggested is not to treat the involved cornea by any specific procedure.


Utrastructure of the cement gland of Xenopus laevis. To establish a morphological baseline for experimental studies of differentiation using the cement gland as a model, the following observations are added to those on record. The elongated cells of Xenopus laevis cement glands have an internal organization displaying five distinct zones differing in structure and specialized function. The apical zone contains packed secretion vesicles apparently belonging to two different types. The transit zone appears to be devoid of major biosynthetic activity and contains secretion vesicles migrating toward the surface. The zone of biosynthesis is typically organized in concentric regions. The very elongated nucleus lies in the next zone. Finally, the storage zone is characterized by lipid droplets and yolk platelets. Only quantitative differences are observed between cells of young and mature cement glands. Though all cells have the same general organization they may probably be divided into two subtypes according to the structure of their cytoplasm. The epithelial cells surrounding the gland differ according to their position along lateral or basal borders.


Circadian influence on the frequency of labeled mitoses method in the stratified squamous epithelium of the mouse esophagus and tongue. The frequency of labeled mitoses method (FLM) was used to study the cell kinetics in the stratified squamous epithelium of the mouse esophagus and tongue. FLMs were generated by injecting tritiated thymidine (TdR) at two different phases of the mouse circadian system: TdR was injected into one group of mice at 0900 and into a different, second group of mice at 2100. Three variables were monitored for each group; (1) the FLM, (2) the mitotic index and (3) the grain count over the labeled mitotic figures. In both the esophagus and the tongue there was a circadian rhythm in the mitotic index with the peak occurring during the first half of the diurnal phase and the trough occurring during the first half of the nocturnal phase. The FLM curves from each group revealed the following data.


Ultrastructure of the indifferent gonad in male and female pig embryos. Pig embryos aged 24 days were obtained from artifically inseminated sows for ultrastructural study of the indifferent gonads. Sex was identified by chromosome analysis. The gonads are composed in both sexes of three different tissues: the surface epithelium, the gonadal blastema and the mesenchyme. The surface epithelial cells contained elongate mitochondria, granular endoplasmic reticulum, free polysomes, the Golgi complex, fine filaments and coated vesicles. The primitive cords were continuous with the surface epithelium and the interior of the gonad was occupied by blastema cells. They had prominent nucleoli, elongate mitochondria, granular endoplasmic reticulum, the Golgi complex, free polysomes, some lipid droplets and occasionally circular smooth membrane profiles resembling the agranular endoplasmic reticulum. Individual primordial germ cells were seen in all parts of the gonad. They were roundish with prominent nucleoli, globular mitochondria, granular endoplasmic reticulum, free polysomes, the Golgi complex, coated vesicles, lipid droplets and dense bodies. Degenerating cells and cells having pseudopods were also encountered. In comparison to the gonad at the age of 22 days, the primordium had grown into a longitudinal roundish protrusion and the number of primoridal germ cells had increased. Histological and ultrastructural observations showed that the pig gonads at the age of 24 days were similar in both sexes.


Morphological changes in the trophoblast, uterus and corpus luteum during delayed implantation and implantation in the western spotted skunk. Morphological interactions of tropholbast and uterus from stages of preimplantation and implantation were studied in 14 western spotted skunks. In addition, the granulosa lutein cells and plasma progesterone levels were studied. In animals several days from implantation the height of epithelial cells decreased, but began to increase in animals approaching implantation. During the preimplantation period a few leucocytes infiltrated the epithelium, but in animals just prior to implantation many leucocytes infiltrated the epithelium.


High-speed liquid chromatographic determination of canrenone in pharmaceutical dosage forms. Canrenone can be determined by high-speed liquid chromatography in pharmaceutical dosage forms without interference from common excipients or degradation products. This stability-indicating assay, using o-nitroaniline as the internal standard, is rapid and accurate.


Sequential chamber localization--logical approach to diagnosis in congenital heart disease. A nomenclature is described for congenital heart disease employing sequential chamber localization. It is an eclectic system based in part upon the previous classifications of Van Praagh and Kirklin. It links together the atrial, ventricular, and arterial segments of the heart and then permits tabulation of associated anomalies. The atrial segment of the heart can exist as situs solitus, situs inversus, or situs ambiguus. Atrioventricular connexions can be concordant or discordant. In certain circumstances the terms concordant and discordant cannot be used. These are in the presence of primitive ventricle and in the presence of situs ambiguus. Alternative terms are described for these contingencies. Ventriculo-arterial connexions can be (a) normal; (b) transposition; (c) double outlet ventricle; or (d) single arterial trunk. These are defined as connexions; relations are relegated to secondary position. Associated anomalies are categorized in terms of venous return, atria, atrioventricular junction, ventricles, and great arteries. Controversial topics are discussed with regard to previous definitions.


Rules for diagnosis of arterioventricular discordances and spatial identification of ventricles. Crossed great arteries and transposition of the great arteries. Rules are presented for the diagnosis of arterioventricular discordances and the spatial position of the ventricles in these cardiopathies by means of angiocardiography and the position of cardiac catheters. Because these rules are based on previous anatomo-embryological findings, the normal development of the conus and the truncus is briefly analysed. The probable morphogenesis of this group of truncoconal cardiopathies is discussed. The fundamental process required to establish the diagnosis of these cardiopathies is as follows: 1) The truncoconal morphology is identified in the lateral projection. a) The anterior position of the pulmonary artery and its infundibulum with respect to the aorta and its infundibulum is characteristic of crossed great arteries with arterioventricular concordance or discordance. b) The anterior position of the aorta and its infundibulum with respect to the pulmonary artery and its infundibulum is characteristic of transposition of the great arteries with arterioventricular concordance or discordance. 2) Once the truncoconal morphology is identified, the use of the anteroposterior projection allows the establishment of the differential diagnosis between arterioventricular concordances and discordances, and of the spatial location of the ventricles in these entities. a) An anterior pulmonary artery directed from right to left, emerging from an infundibulum placed on the left side (anatomically right ventricle on the left) or an anterior pulmonary artery directed from left to right, arising from an infundibulum located to the right (anatomically right ventricular placed on the right), is the specific image of discordant crossed great arteries. b) An anterior pulmonary artery directed from right to left emerging from an infundibulum placed on the right side (anatomically right ventricle on the right side) or the anterior pulmonary artery directed from left to right arising from a left-sided infundibulum (anatomically right ventricle placed on the left side) is characteristic of concordant crossed great arteries. c) An anterior aorta placed to the right of the pulmonary artery and emerging from a left-sided infundibulum (anatomically right ventricle placed on the left side) or an anterior aorta placed to the left of the pulmonary artery and arising from an infundibulum placed on the right side (anatomically right ventricle placed on the right) is characteristic of discordant transposition of the great arteries. d) An anterior aorta placed to the right of the pulmonary artery emerging from a right-sided infundibulum (anatomically right ventricle placed on the right) or an anterior aorta placed to the left of the pulmonary artery arising from an infundibulum placed on the left (anatomically right ventricle placed on the left) is the specific picture of concordant transposition of the great arteries...


Catheter mapping of retrograde atrial activation. Observations during ventricular pacing and AV nodal re-entrant paroxysmal tachycardia. A systematic study of retrograde atrial sequence at commonly used electrode catheter recording sites in 8 patients without, and in 4 patients with AV nodal re-entrant paroxysmal tachycardia was made. During right ventricular pacing, the retrograde atrial activation sequence was low septal right atrium--proximal coronary sinus--distal coronary sinus--high right atrium. During the episodes of paroxysmal tachycardia, a similar pattern was observed. This information should be helpful in the understanding of abnormal activation sequences in patients with paroxysmal supraventricular tachycardia in whom retrogradely conducting anomalous pathways are suspected.


Effects of pacing site on QRS morphology in Wolff-Parkinson-White syndrome, with special reference to 'pseudo-tachycardia-dependent block in accessory pathway and 'atrial gap'. In a patient with a Wolff-Parkinson-White (WPW) syndrome type A mid-right atrial stimulation at a rate of 73/min produced a lesser degree of ventricular pre-excitation than when a slower sinus rhythm was present. This paradoxical effect was not related to tachycardia-dependent block in the accessory pathway because pre-excitation again increased at faster pacing rates. It was partly the result of a (proportionally) greater prolongation of intra-atrial conduction time to the accessory pathway than to the atrioventricular node and partly of a faster atrioventricular nodal conduction time. The latter, in turn, could be attributed either to later-than-normal arrival of excitation at the atrioventricular node, at a time when this structure was more recovered, or to a change in the site or mode of entry into the atrioventricular node. A gap in the atria was present because at a St1-St2 interval shorter than that which A2 had been blocked in the accessory pathway conduction was again possible, but with longer A1-A2 intervals. Finally, at similar, short, coupling intervals the impulse penetrated the atrioventricular node from the mid-right atrium but not from the coronary sinus. The unusual findings in this case support a recent assumption that in patients with WPW type A atrial stimulation should be performed from the coronary sinus to minimize the potential sources of error which can be produced by intra-atrial delay.


Coarctation of the aorta in infancy and childhood. The management and results of treatment in 181 children with coarctation of the aorta are presented. In this series, 79% of the patients presented in the first year of life and 55% presented as neonates. One hundred and fifty patients were operated on, with a total surgical mortality of 21%. Only one surgical death occurred in those operated on after 3 months of age. The higher mortality in young infants is closely related to associated cardiac anomalies and to the frequency of aortic and isthmal hypoplasia. Our findings suggest that neonates presenting with heart failure and coarctation should be operated on early, as the surgical mortality under 6 weeks is 45%, whereas there is an 86% mortality in neonates who were not operated on. Analysis of follow-up indicates that when operation can be performed electively the optimal period for sugical treatment is between 6 months and 1 year of age. If operation is performed after this age, there may be persistent systemic hypertension despite relief of aortic obstruction.


Comparison of single and biplane ejection fractions in patients with Ischaemic heart disease. Simultaneous biplane left ventriculography was performed in 59 patients with ischaemic heart disease. A comparison was made of the frontal (EFF), lateral (EFL), and biplane (EFB) ejection fractions. Discrepancies between the three measurements in the same patient were frequent observed. The patients were then grouped according to the presence or absence of signs of transmural myocardial infarction in the electrocardiogram or wall motion abnormalities, and the single and biplane EF data were again compared. There were 31 patients with previous transmural myocardial infarction and 37 patients with wall motion abnormalities, usually involving the anterior or inferior walls. The EFL of patients with transmural myocardial infarction or wall motion abnormalities commonly exceeded the EEF, because of frequent preservation of dorsal wall contraction visualized only in the lateral plane. Consequently, there was a significant difference between EFF or EFL and EFB for these patients. In contrast, there was close agreement EEF and EFL for patients without transmural myocardial infarction or wall motion abnormalities. It is concluded that differences frequently occur between single and biplane EF in patients with ischaemic heart disease, especially if transmural myocardial infarction or wall motion abnormalities are present. Hence, accurate assessment of left ventricular performance is greatly facilitated by simultaneous or sequential biplane ventriculography.


Vigorous exercise in leisure time, coronary risk-factors, and resting electrocardiogram in middle-aged male civil servants. During 1968 to 1970, approximately 17 000 middle-aged male executive grade civil service officers, all of them engaged in sedentary or very light work, recorded on a Monday morning their leisure time activities over the previous Friday and Saturday. In 1971 a sample of 509 of these men completed further questionnaires for medical, social, and smoking history; these men had a resting electrocardiogram, and height, weight, skinfold thickness, blood pressure, and plasma total cholesterol were measured. Vigorous exercise in leisure time had previously been reported by 125 (25%) of the men, and these as a group had significantly fewer electrocardiographic abnormalities (changes compatible with myocardial ischaemia, ectopic beats, and sinus tachycardia) than the men not reporting vigorous exercise (P less than 0-02). This difference remained when all men with any history suggestive of cardiovascular disease were excluded from the analysis. Blood pressure, plasma total cholesterol, and smoking habits were examined with respect both to vigorous exercise and to the electrocardiogram, but the only relation found was that electrocardiographic abnormality increased with increasing blood pressure. Even among men with higher pressures, however, those reporting vigorous exercise had fewer electrographic abnormalities than the others. The results provide further support for the association of habitual physical activity with coronary health.


Sinoatrial disease in acute myocardial infarction. Long-term prognosis. Of 32 patients with acute myocardial infarction complicated by sinoatrial disease, 23 survived. All 23 had inferior infarction. During follow-up lasting 4 to 6 years only one patient developed severe chronic sinoatrial disease (sick sinus syndrome) necessitating permanent pacemaker treatment; twelve others died during this time. In 2 of them death was sudden 5 and 6 months after infarction. Atrial pacing studies in 7 of the 11 patients still alive showed no gross abnormalities. A review of 71 patients with chronic sinoatrial disease treated with a permanent pacemaker revealed only 5 with previous documented infarction. The present data suggest that sinus node dysfunction in patients surviving acute infarction is most often only temporary as is atrioventricular block. Occasionally, however, severe chronic sinoatrial disease requiring a permanent pacemaker may develop later, and this course of events is most likely to occur in those patients who had additional complications during the acute infarct.


Successful electrical pacing for complete heart block complicating diphtheritic myocarditis. A case of severe diphtheria complicated by myocarditis and neurorespiratory paralysis is reported. The myocarditis manifested with severe conduction disturbances including left bundle-branch block and high grade second degree atrioventricular block leading to Adams-Stokes attacks. Temporary transvenous electrical pacing for.3 days was successful in the management of this complication, but positive pressure ventilation was later required for respiratory paralysis. This case illustrates the potential value of electrical pacing in diphtheritic myocarditis. Sporadic cases of diphtheria still occur and the case fatality ratio remains at 10%, much of which is related to the occurrence of myocarditis.


Spontaneous variations in atrioventricular conduction in pre-excitation. Atrial pacing in a patient with a Wolff-Parkinson-White syndrome pattern showed unusual variability in AV nodal conduction time. Changes in the AV nodal conduction time occurred predominantly at paced rates in excess of 100/min and consisted of abrupt or gradual decreases in the AH interval. Such decreases resulted in unexpected normalization of the QRS pattern. In addition, pacing also revealed evidence of block in the accessory pathway. Such changes in atrioventricular conduction may account for the known variability of the QRS pattern in patients with the WPW syndrome. Further, they may also explain the benign clinical course in this patient.


Transcutaneous aortovelography. A quantitative evaluation. The haemotachograph is a non-invasive ultrasonic Doppler-shift instrument designed to measure the velocity of blood in the arch of the aorta by a technique referred to as transcutaneous aortovelography. Its accuracy has been assessed at cardiac catheterization in 20 patients. When transcutaneous aortovelographic values were compared with stroke volume determined by standard invasive techniques, a good proportional agreement was found. The accuracy of absolute flow values, as calculated from transcutaneous aortovelography and dimensional data, was, however, poor. Peak velocity determined from transcutaneous aortovelographic tracings agreed well with values obtained with a catheter tip electromagnetic velocity probe. Transcutaneous aortovelography is a useful non-invasive technique which can be used to determine phasic blood flow velocity in the aortic arch and to follow changes in cardiac output over a period of time.


Transcutaneous aortovelography. Potentially useful technique in management of critically ill patients. Pilot evaluation of the clinical use of transcutaneous aortovelography has been undertaken and suggests that this technique will be useful in the assessment of left ventricular function in the acutely ill patient. Changes in waveform as a result of therapy or alteration in clinical condition can frequently be noted by critical visual assessment. Increasing clinical experience suggests that quantification will permit interpretation of less obvious changes in the recorded waveform. Transcutaneous aortovelography has the simplicity, speed, and safety afforded by a non-invasive technique.


Incidence of arrhythmias induced by isometric and dynamic exercise. The incidence of arrhythmias during isometric sustained handgrip exercise and during dynamic graded bicycle exercise was compared in a group of 45 patients with various forms of heart disease on no antiarrhythmic therapy. Atrial arrhythmias were equally common during handgrip and bicycle exercise but ventricular arrhythmias were more frequent during handgrip exercise. Of the 45 patients, 38 per cent developed ventricular arrhythmias during isometric exercise, with ventricular tachycardia occurring in 15 per cent. During dynamic exercise 22 per cent of the 45 patients developed ventricular arrhythmias, with ventricular tachycardia occurring in 2 per cent. Patients with coronary artery disease and/or depressed left ventricular function developed twice the incidence of ventricular arrhythmias with isometric than with dynamic exercise. Thus, isometric exercise testing is of more value than dynamic exercise testing in unmasking latent ventricular arrhythmias in patients with heart disease.


Interaction between cardiovascular responses to sustained handgrip and Valsalva manoeuvre. Interactions between the cardiovascular responses to the Valsalva manoeuvre and sustained handgrip were analysed in 5 men with untreated mild hypertension and 4 young normal subjects. Though set at a higher level, there was a normal blood pressure response to the Valsalva manoeuvre during concurrent sustained handgrip in 4 of the 5 hypertensive subjects. At the end of the handgrip period in which the Valsalva manoeuvres were performed, the blood pressure was higher and the heart rate lower than in the control period of sustained handgrip. The fifth subject developed a 'square wave' Valsalva response, which returned to a normal response when sustained handgrip was discontinued. Analysis of RR interval changes in the normal subjects showed that both the tachycardia during, and the bradycardia after, the Valsalva strain period were significantly reduced during simultaneous sustained handgrip. These results show that the two reflexes interact, but only to a minor extent, and that the baroreflex response is modified by sustained handgrip, rather than overridden as had previously been suggested. In view of the effect on the blood pressure and heart rate, subjects should avoid performing a Valsalva manoeuvre during sustained handgrip testing.


Left ventricular function after aortic valve replacement. Changes in haemodynamics and in systolic time intervals, early after valve replacement, were studied in a group of 15 patients. Though all the haemodynamic measurements were within normal limits at 44 hours after operation, there was a persistent change in systolic time intervals (shortening of left ventricular ejection time and electromechanical systole, and prolongation of pre-ejection period and increase in the ratio PEP/LVET). The effect of periods of myocardial ischaemia during cardiopulmonary bypass on myocardial function is suggested as the explanation for the changes observed.


Anomalous iliac compliance in children with a single umbilical artery. Arterial compliance (C) has been measured in 18 children known to have had a single umbilical artery at birth. Non-invasive ultrasonic Doppler techniques were used to measure C for the aorta, iliac, and leg arteries. Anomalous compliance was found between the two iliac vessels, and it is suggested that this is the result of haemodynamic stress-induced changes during development. The demonstration that the form of large arteries may be changed by altered haemodynamic stress and that their physiological function is thus affected, may have important implications in the pathogenesis of degenerative disease.


Relationship between antigenicity and morphology of murine lung adenomata. Thirty-six lung adenomata induced in mice by urethane followed or not by cortisone, all had an adenomatous morphology at first s.c. transplant in syngeneic hosts. Seventeen of them acquired a sarcomatous structure within a few s.c. transplant generations whilst the other 19 remained adenomatous for as long as tested, i.e. at least 10 transplant generations. The change of  morphology was not dependent on s.c. growth, since tumours also transformed when allowed to grow in the lung, and was not correlated to the capacity of a tumour for growth or metastasis. The 2 types of tumours were antigenically different, since only tumours that after few transplants changed their morphology were found at the first s.c. transplant to possess tumour-associated membrane antigens as revealed by an in vitro test. In addition, only the tumours which acquired a sarcomatous morphology were found gs-positive. The majority of antigenic primary tumours arose in mice belonging to the groups of treatment which induced the strongest immunodepression. It is suggested that a predisposition to sarcoma progression is related to an immunological control, at the time of adenoma induction, of an oncornavirus, responsible for the superimposed sarcomatous change.


Carcinoembryonic antigen: isolation of a sub-fraction with high specific activity. Four sub-fractions of carcinoembryonic antigen have been obtained by chromatography of conventional CEA on Con A-Sepharose and their immunoreactive contents have been determined. Comparative studies have shown that a fraction eluted with 2% methyl glucoside (CEA 2B) had the highest activity, with a potency (60 u/mug) twice that of unfractionated CEA although appreciable activity was also found in the other fractions. The amino acid composition of CEA 2B is similar to that reported for conventional CEA but there is a lower content of neutral hexoses and a comparatively high content of N-acetylglucosamine. Experiments with a pool of sera from 11 patients with colonic cancer, which had been fractionated on Con A-Sepharose, have shown that nearly all the CEA activity was contained in a fraction eluted with 2% methyl glucoside. A convenient method of isolating CEA with high specific activity directly from perchloric acid extracts of tumour tissue is also described.


Influence of leukaemic cells on the colony formation of human bone marrow cells in vitro II. Suppressive effects of leukaemic cell extracts. The influence of leukaemic cells on the colony formation of human bone marrow cells was studied in vitro as an extension of our previous work (Chiyoda et al., 1975). An extract of leukaemic bone marrow cells significantly suppressed colony forming ability of the normal bone marrow cells, whereas an extract of normal bone marrow cells did not suppress it except in two cases. The suppressive effect of normal bone marrow cells, however, was obviously less intense than that of leukaemic cells. This suppressive effect was dose dependent and was fairly stable to heat treatment. These results suggest that leukaemic bone marrow cells contain factor(s) which suppress normal colony formation.


Antitumour activity of adenovirus-12 structural proteins against Moloney sarcoma tumours in mice. When purified fibre and hexon proteins of adenovirus 12 were given intramuscularly to 4-week-old BALB/c mice (250-300 mug/mouse) 2 h prior to inoculation with mouse sarcoma virus (0.05 ml of 10(4) FFU/ml) at the same site, significant suppression of tumour growth (P less than 0.001), and rapid regression in tumour size (P less than 0.001) were noted. As a rule, the survival rate in treated mice was also significantly higher than in untreated mice. Furthermore, the disease process in treated mice as compared to untreated mice was far less extensive as judged by the scarcity of sarcoma lesions on the spleens. Preliminary evidence suggested that treatment with fibre could lead to increased cellular immunity in mice. Whether this may be a secondary consequence of events whereby fibre inhibited tumour growth rather than first order mechanism of the inhibition is not known.


Stimulation of cellular ingestion by basic proteins in vitro. The ingestion of carbon and benzpyrene particles in vitro by rat peritoneal macrophages, baby hamster kidney fibroblasts (BHK-21) and mouse L-cells has been shown to be significantly stimulated by the inclusion of histone or polylysine in the culture medium. Parallel studies using methylated bovine albumin did not significantly stimulate carbon or benzpyrene uptake relative to untreated control cultures. Incubation of carbon particles with histone before inclusion in the culture medium of macrophages resulted in the same degree of uptake as in the cultures where carbon and histone were added independently of each other. The implications of these findings to in vivo chemical carcinogenesis are examined.


Carcinogenic effects of different nitroso-compounds in Chinese hamsters. I. Dimethylnitrosamine and N-diethylnitrosamine. Three hundred and twenty Chinese hamsters (Cricetulus griseus) (CH) were treated (s.c.) with 1/5, 1/10 or 1/20 LD50 of dimethylnitrosamine (DMN) or N-diethylnitrosamine (DEN). These substances, in several respects, showed a different organotropy in this species than in both the Syrian golden (SGH) and the European hamster (EH). In CH, DEN produced up to 100% squamous cell papillomata and occasionally also carcinomata of the cheek pouch, tongue, pharynix, oesophagus and forestomach. With DEN a high rate of hepatomata was simultaneously realized. DMN induced a considerable quantity of liver tumours, the highest incidence being demonstrated in the lowest dosage group.


The roles of age at treatment and dose in carcinogenesis in C3Hf/Dp mice with a single administration of N-nitroso-N-methylurea. C3Hf/Dp mice were given a single i.p. injection of 50, 25 or 5 mug/g N-Nitroso-N-Methylurea (NMU) at either 1 or 70 days of age or 50 mug/g at 21 days of age. They were observed until death or until 120 weeks of age. The two highest doses of NMU produced tumours in a wide spectrum of organs, including the thymus, forestomach, lung, liver (only in males), kidneys, ovaries and orbital glands. The only two tumour types which appeared to be closely related to the occurrence of death were thymic lymphomata (most of which were found in mice dying before 40 weeks after treatment) and carcinomata of the forestomach. Lifetime analyses are presented concerning the occurrence of these two tumour types as well as the occurrence of any tumour after 40 weeks of age or since treatment. Incidences of thymic lymphomata were 67.6%, 39.0% and 21.2% in mice receiving 50 mug/g NMU at 1, 21 and 70 days respectively and 17.1% in mice receiving 25 mug/g at 1 day. In the other groups the incidence of thymic lymphomata was zero or negligible. The rate of progression of thymic lymphomata until death was related to both earliness of treatment and dose. On the contrary, incidences and progression of carcinomata of the forestomach were unrelated to age at treatment. Since breakdown of NMU is very rapid and does not require enzymes, these results are considered as evidence that host-tumour interaction differs from organ to organ. No excess of tumours over the controls was found in mice receiving 5 mug/g either at 1 or 70 days of age.


The results of diethylstilboestrol therapy for recurrent and metastatic carcinoma of the male breast. A retrospective survey has been made of 58 patients with recurrent and advanced male breast cancer treated with oral diethylstilboestrol. Fifty-five patients were suitable for assessment. Fourteen patients had an objective response and 7 had a partial response giving a total response of 21/55 patients (38%). The median remission for the objective responders was 7 years. Three patients are alive and free of disease; one has now been in remission for 13 years. It is suggested that diethylstilboestrol is a useful treatment in patients with soft tissue disease (breast, chest wall and/or lymph nodes).


The reversibility by dipyridamole of the increased sensitivity of in vivo platelet aggregation in rabbits after alloxan. Rabbits hyperglycaemic after previous intravenous injection with alloxan show an increased sensitivity of the aggregation of platelets to adenosine diphosphate applied topically to injured arteries. This increased sensitivity is completely reversed by treatment with oral dipyridamole but returns if the dipyridamole is withdrawn.


The hepatotoxicity of O,O-diethyl, O-phenyl phosphorothionate (SV1) for the rat. The parathion analogue O, O-diethyl, O-phenyl phosphorothionate (SV1) is hepatotoxic when given in large intraperitoneal doses (400 mg/kg body weight) to male rats that have been treated previously with phenobarbitone. The lesion produced at 24 h after dosing is a periacinar hydropic degeneration which appears identical to that caused by carbon disulphide (CS2) in similarly pretreated rats. Both lesions are characterized by a marked depression in hepatic microsomal cytochrome P-450 levels, no change in the concentrations of Na+, K+ and Ca++ in liver water, in contrast to the periacinar necrogenic lesion caused by tccl4 in which Na+ and Ca++ levels markedly increase while that of K+ decreases. The similarity of the SV1 and CS2 induced liver changes, the fact that both chemicals undergo a similar oxidative desulphuration in the liver microsomes and that prior induction of the latter enzymes is necessary in order to produce the injury suggest a similar mechanism for both lesions. A reactive form of sulphur released from the metabolism of CS2 and phosphorothionates in the liver may become covalently bound to constituents of the endoplasmic reticulum of the liver cell and in this way initiate the toxic liver changes. Drugs and chemicals which contain P=S or C=S bonds and which undergo oxidative desulphuration in the liver could thus be similarly hepatotoxic.


Glomerular lesions in experimental renal papillary necrosis. I. Ultrastructural aspects and some pathogenic considerations. Papillary necrosis was induced in rats by a single intravenous injection of bromoethylamine hydrobromide (BEA). From 7 days on glomerular lesions were recognized. They consisted of electron dense deposits mainly subepithelial in location; mild mesangial hypercellularity and matrix increase. Immunofluorescence with anti-rat gammaglobulin was positive, showing granular fluorescence in relation with basement membrane and mesangium. The possibility is raised that these lesions are due to the pathogenic action of immune complexes, the antigen being one arising during the necrosis of the renal papilla. It is also suggested that this mechanism can be operative in ths human being in cases of papillary necrosis of the kidney.


The behaviour in ferrets of two closely related clones of influenza virus of differing virulence for man. Clones 7a and 64d of the recombinant influenza virus A/PR/8/34-A/England/939/69(H3N2) which are of different virulence for man as judged by clinical score (7a more virulent than 64d) showed similar differences in ferrets. With intranasal inoculation the approximate 50% minimal infectious doses of both clones were similar (between 10(0) and 10(2) EID(50)) as were their titres in nasal washes 24 h after inoculation and the histologically evident damage they caused in the nasal turbinates. However, clone 7a persisted in the nasal washes more than 64d and produced a more prolonged pyrexia. Furthermore, 7a consistently produced a lung infection which was produced only occasionally by 64d and then to a lesser extent than 7a. In contrast to nasal mucosa, histological damage in the lung was slight with both strains. Differences in replication of 7a and 64d in organ cultures of nasal turbinates appeared only after 24 h incubation. They were not sufficiently large to explain the markedly superior ability of 7a to persist in the nasal tract in vivo. This persistence, which coincides with the production of pyrexia, may be due to a greater ability of 7a to resist induced systemic host defences. Spasmodic isolations of infective virus of both clones were made from extra-respiratory tissues such as liver, spleen and kidney.


The ultrastructure of the reaction of arterial walls to cholesterol crystals in atheroembolism. Scanning electron microscopy of atheromatous material revealed flat rhombic cholesterol crystals piled one upon the other. The fate of cholesterol crystals in the atheromatous material was followed after injection intra-arterially into the left renal arteries and left common carotid arteries of rabbits. The lipid and membranous component of the atheromatous material disappeared from the lumen of the vessels in 2-3 days after injection. Macrophages engulfed small cholesterol crystals and exposed surfaces attracted a layer of platelets. Larger cholesterol crystals evoked a giant cell response while within the lumen. Some cholesterol crystals penetrated the vessel walls or were included in the vessel wall reaction and induced a covering of endothelial cells sequestrating them from the lumen. The cholesterol crystals contained in some of the macrophages showed fracture lines and in some instances there were associated myelin figures. Large cholesterol crystals eventually elicited a fibroblastic response from the vessel wall (at about 1-4 weeks after injection) which could give rise to partial or almost complete occlusion of the vessel lumen.


Cellular proliferation in the urinary tract epithelium of the rat following temporary unilateral renal ischaemia. A study of the effect of temporary unilateral renal ischaemia on the epithelium lining the renal pelvis and the bladder of the rat is described. There is a significant increase in the mitotic index in the pelvic epithelium of the affected kidneys, presenting a well-defined peak approximately 36 h after reflow. A similar but less pronounced cellular proliferation occurs in the bladder epithelium. The increased mitotic index in the renal pelvis and the bladder is not preceded by any detectable cell destruction at either site. It also has a different time course from the tubular regeneration which follows renal ischaemia.


A quantitative assessment of the structural changes the rat's liver following obstruction of the common bile duct. A study has been made of sequential changes in the rat's liver from 1 to 40 days after obstruction of the common bile duct. The qualitative changes have been described and illustrated. The volume proportions of hepatocytes, bile duct epithelium and biliary stroma have been quantified by histological analysis using a point counting technique. The proliferation of hepatocytes and bile duct cells have been measured by labelling with tritiated thymidine. The absolute quantity of hepatocytes in each liver has been estimated and expressed as a percentage of body weight. Over 40 days there is a relative fall in the volume proportion of hepatocytes and an increase in bile duct cells and biliary stroma. These changes in volume proportions are related directly to the period of jaundice. Biliary stroma increases in support of new bile duct tissue and there is no excessive fibrosis. Hepatocytes proliferate at a greater rate than normal after obstruction of the common bile duct and the degree of proliferation reaches a maximum of 24 times that of normal 4 days after obstruction. Similarly, the proliferation of bile duct epithelium is increased in obstructive jaundice but in this instance it reaches a maximum of 50 times that of normal 24 h after ligation of the common bile duct. The absolute quantity of hepatocytes in the liver probably falls during the period of jaundice. However, the fall is less than anticipated from the volume proportion of hepatocytes because of the overall increase in liver size.


Studies of the morphology and tumorigenicity of experimental brain tumours in tissue culture. Brain tumours induced transplacentally in BD-IX rats by a single dose of N-ethyl-N-nitrosourea have been successfully grown in tissue culture. These tumours were malignant pleomorphic gliomas. The cultured cells retained their glial morphology both in vitro and on reinjection into syngeneic hosts: astrocytes became the predominant cell type. The ability of the cells to form tumours increased with time in culture as reflected both in the decreased latency of the tumours and in the increased ability of the cells to grow in semi-solid medium.


Factors influencing the survival of cell monolayers during storage at 4 degrees. As a step towards the definition of a medium suitable for long-term storage of potential organ transplants, a study was made of the effects of various solutions on the viability of monolayers of cells stored at 4 degrees. It was found that, for these to survive for more than a few hours, an essential component of the medium was a non-toxic solute which did not cross the cell membrane at low temperatures and could therefore counterbalance the osmotic effect of the intracellular proteins. A high K+/Na+ ratio and hyperosmoticity, separately or together, were ineffective in the absence ofsuch a solute and unnecessary in its presence. The most effective non-permeating solute tested was polyethylene glycol, mol. wt. 20,000 cells stored in a 1% solution of this in phosphate buffered balanced salt solution remained viable for at least 24 hours and could subsequently be grown in culture.


The pathogenesis and pathology of experimental Quaranfil virus infection. Mice were infected intranasally with Quaranfil arbovirus, and killed at intervals from 1 day to 2 months later. The infection produced clinical signs of neurological disturbance and a highly mortality. The virus could be isolated from the lungs on Days 1-9 and from the brain on Days 1-11 of the infection. Meningoencephalitis developed by Day 5 in the olfactory lobes and spread progressively caudally, involving all regions of the brain by Day 7. The prinicipal features of the inflammatory process were perivascular cuffing, necrosis of neurones, and, in the later stages, spongiform degeneration and marked astrocytic and microglial activity. In the lungs after a short and mild exudative phase interstitial pneumonia developed. This was characterized by proliferation of connective tissue cells in interalveolar septa and later by fibrosis.


Acute and protracted changes in the liver of Syrian hamsters induced by a single dose of aflatoxin B1. Observations on pathological effects of the solvent (dimethylformamide). Male Syrian hamsters, 8-10 weeks of age, were treated with a single intraperitoneal injection of crystalline aflatoxin B1 in solution of N -N -Dimethylformamide (DMF). The concentrations of aflatoxin were adjusted to the smallest controllable amount of solvent in relation to the size of the animal (0-5 or 1-0 ml/kg). Treatment with, respectively, 5-0 or 2-5 mg/kg aflatoxin in 1-0 ml/kg DMF was lethal to most animals within one week. However, reduction of the solvent to 0-5 ml/kg, while not eliminating the mortality entirely during the first week, made possible observation of the survivors up to 28 days. Hamsters appear to be more susceptible to DMF poisoning than other species, like rat, guinea-pig and rabbit in which this solvent was used by investigators on the biological effects of aflatoxin. Either dose given of DMF alone was lethal for several animals during the first week of observation and sufficient to produce histological lesions in the liver which were characteristic and clearly different from those induced by aflatoxin during the same period. DMF alone caused centrilobular necrosis which was accompanied by haemosiderosis of liver structures. With a aflatoxin, in addition, periportal and midzonal necrosis of the liver was present. Aflatoxin B1 and B1 and DMF both induce haemorrhagic tendency probably involvement in the coagulation process of the blood. It cannot be decided, however, at present whether this is the result of an indentical mechanism.


Veno-occlusive lesions in the liver of rats after prolonged feeding with palmyrah (Borassus flabellifer) flour. Flour from the young shoot of the palmyrah palm (Borassus flabellifer) which is consumed by people in certain tropical countries, when fed for prolonged periods to adult male rats produced chronic hepatic lesions which included intraluminal fibrosis of the centrilobular and portal veins, bile duct proliferation, increase of reticulin and fibrosis. Thromboses of the hepatic veins was not seen. The vascular lesions commenced as a subendothelial swelling which projected into the lumen and in which collagen deposition ended in almost total obliteration of the lumen. No hepatic megalocytosis was seen. It is suggested that the toxic factor(s) responsible are different from the pyrrolizidine alkaloids and dimethylnitrosamine which have been well documented to produce similar lesions.


The cell proliferation kinetics of psoriasis examined by three in vivo techniques. The cell proliferation kinetics of the germinative compartment in psoriasis have been re-investigated with tritiated thymidine and vincristine techniques. The mean cell cycle durations calculated from an extended fraction of labelled mitoses experiment were Tc=56 h, t1=43 h, ts=7-7 h and t2=5-6 h. Combination of the results of the FLM experiment with the experimental labelling index and the experimental birth rate suggests a growth fraction of unity and an exponential age distribution for the germinative population. An exponential age distribution is supported by the presence of several layers of germinative cells and the direction of the mitotic axes during cell division.


Simplification of local therapy of psoriasis with 8-methoxypsoralen. Methods and initial results. Local 8-methoxypsoralen black-light treatment was carried out on sixty-two patients. For the first time, oil was employed as a preparation base in order to increase the transparency and so the effectiveness of irradiation. Also the need for a descaling pretreatment was avoided. In investigations still being carried out, 27.5% patients showed very good improvement, 48-4% good and 24-2% unsatisfactory results of treatment. In many cases, less than fifteen irradiation sessions were necessary for clinical healing. However, to obtain a uniform pigmentation, additional irradiation proved necessary.


Epidermal lipid metabolism in psoriasis and lichen simplex. The rate and pattern of epidermal lipogenesis from [14C] glucose were measured in fifteen patients with psoriasis and three with lichen simplex, compared with twenty controls. In 'uninvolved' epidermis from psoriatic subjects the mean lipogenic rate was slightly raised, although the increase was not statistically significant. There was a positive correlation between overall lipogenic rate and the percentage of isotope appearing in free sterol, while the relative proportions of the other lipid classes were unchanged. By contrast, in control epidermis sterol percentage was negatively correlated with lipogenic rate. In psoriatic lesions total epidermal lipogenesis (per unit surface area) was raised compared with matched control 'uninvolved' epidermis. Also raised were percentage labelling of free sterol and of combined (free sterol and monoesters), and the free sterol: monoester ratio was increased. Similar findings were obtained with lesions of lichen simplex, suggesting that disturbed sterol metabolism may be a common feature in conditions of abnormal keratinization.


The natural history of trichilemmal cysts. The histological features of 149 trichilemmal cysts removed from sixty-five patients are reviewed and related to the clinical findings. These cysts, which may be solitary or multiple, gradually increase in size and number, and may produce daughter cysts by budding. When a breach occurs in the wall, inflammatory cells pour in but do not replace the cyst wall. This event may be followed by healing from the margins of the breach, by marsupialization to the overlying epidermis and thus natural resolution, or by proliferation to produce a pseudo-epitheliomatous change which can be confused with a well differentiated squamous cell carcinoma.


Wegener's granulomatosis. Combined therapy with low-dosage systemic corticosteroids, azathioprine and cyclophosphamide in three patients. Three patients with Wegener's granulomatosis are reported. All three had skin, nose, sinus, mouth and pulmonary lesions; one had severe renal involvement as well. In two patients combined treatment with low-dosage systemic corticosteroids, azathioprine, and cyclophosphamide resulted in rapid clinical improvement and complete disappearance of the skin, mouth, nasal, sinus and pulmonary lesions. In one of these two patients who had severe renal involvement, proteinuria greatly diminished and arrest of progression of renal insufficiency was observed. In the third patient combined treatment with azathioprine and cyclophosphamide resulted in complete remission of skin, mucous membrane, lung and sinus lesions. The patient with severe renal involvement is alive and ambulant 4 years after the onset of the disease, the other two are completely symptom-free and well 2 1/2 years and 1 year after the onset of their illnesses, respectively. These results confirm previous reports about the effectiveness of immunosuppressive and cytotoxic agents in Wegener's granulomatosis, the use of which seems to have improved the prognosis significantly in a disease previously considered to be fatal within 5 months.


Challenge test battery in chronic urticaria. The use of a battery of challenge tests in the routine investigations of patients with chronic urticaria has an important place, demonstrating an exacerbating factor in over half the patients. Diets designed to reduce the ingestion of the substances concerned are associated with clearing or considerable improvements in 75% of the patients treated.


Histological aspects of DNCB sensitization and challenge tests. I. A group of twenty-one Caucasian volunteers was patch tested without preliminary sensitization with 3, 10, 30, 50 and 90 mug 2,4-dinitrochlorobenzene (DNCB)/cm2. Of this group seven persons were read after 24 h; with one exception all showed a toxic erythematous reaction to 30 mug and higher amounts of DNCB/cm2. The other fourteen volunteers were read after 48 h. All except one reacted positively to 30 mug and higher amounts of DNCB/cm2. Histologically no changes could be noted after application of 3 and 10 mug DNCB/cm2; they started to appear in patch tests with 30 mug DNCB/cm2 or more. II. A second group of twenty-one Caucasian volunteers was sensitized with 2000 mug DNCB on a surface area of 3-14 cm2. Biopsies were performed after 1 h, 5 h, 1 day and then daily for 17 days. The histological changes occurring in the sensitization site during the primary irritant reaction of the first days were compared with the changes occurring during the flare-up reaction. No essential qualitative differences could be noted. III. Four Caucasian volunteers were sensitized with 2000 mug DNCB on 3-14 cm2. Fourteen days later challenge patch test doses of 3, 10, 30, 50 and 90 mug DNCB/cm2 were applied. Biopsies of the challenge sites were performed after 48 h. In contrast to the results in group I, histological changes could already be noted after challenge patch tests with 3 mug DNCB/cm2. The nature ofthe histological changes in primary irritant and allergic reactions to DNCB appeared to be identical and consisted of spongiosis, epidermal degeneration and lymphocytic infiltration around vessles and epidermal appendages and penetrating into the epidermal layers. It is concluded that, in order to avoid errors through misinterpretation, challenge patch tests with DNCB must be performed with low amounts, e.g. 3 or 10 mug/cm2.


A case of Pyemotes dermatitis. With a note on the role of these mites in skin disease. Acute dermatitis developed in a fisherman after contact with old cherry-wood. A Pyemotes mite, probably P. beckeri, found in the wood, was thought to be responsible--thus illustrating the importance of appropriate laboratory examinations for ectoparasites. Human skin erruptions caused by indigenous, in contrast to imported, Pyemotes species have not previously been reported in Britain. These tarsonemoid mites attack small insect hosts and their possible role in dermatoses is discussed. Dermatitis caused by these mites is probably world-wide in distribution, but during the last century the confusing acarological nomenclature surrounding Pyemotes has resulted in an equally confusing variety of dermatological diagnoses.


Mycobacterium marinum skin infections mimicking cutaneous leishmaniasis. Ten cases of skin infection due to Mycobacterium marinum are reported from Israel. Most of the infections were contracted in natural bathing pools at Ein Feshka on the shores of the Dead Sea, south of Jericho. The lesions closely resembled those of cutaneous leishmaniasis prevalent in this region. The condition does not seem to have been detected previously in the Middle East.


Contact dermatitis from propolis.

Contact dermatitis from propolis. Two patients with contact dermatitis due to the natural product propolis (bee glue) are reported. They presented perioral eczema and stomatitis which were recalcitrant until propolis was considered as the cause. Patch tests with propolis preparations were positive in both patients, and, furthermore, in the second patient the lesions relapsed after provocation tests. European standard patch test including balsam of Peru were negative. The complexity of propolis, its supposed anti-inflammatory effect due to flavonoids, and the sensitizing agents originating mainly from the poplar trees are discussed together with the cross-sensitization to balsam of Peru. Contact dermatitis due to propolis should be considered in unexplained eczemas, mainly perioral but also in other areas, as propolis preparations are available also as ointments and cosmetic creams.


The pathology of lymphangioma circumscriptum. A study of lymphangioma circumscriptum has been carried out over a number of years in an attempt to understand its nature and pathogenesis, with a view to improving treatment. It is postulated that the lesion consists essentially of a collection of large muscular-coated lymphatic cisterns, lying deep in the subcutaneous plane and communicating via dilated dermal lymphatics with the superficial vesicles. It seems that these cisterns do not communicate directly, if at all, with the general lymphatic system but represent a sequestrated part of it. They have been shown by cannulation to pulsate at a slow steady rate producing a rise and fall of pressure within them. It is believed that the vesicles are saccular dilatations of superficial lymphatics, secondary to raised pressure transmitted from the pulsating cisterns beneath. It is suggested that may be possible to treat these lesions more successfully and with better cosmetic results by excising the subcutaneous cisterns and leaving the overlying skin intact.


Vascular changes in human skin after ultraviolet irradiation. Blood-flow changes in human skin after ultraviolet irradiation at 250 and 300 nm have been measured by three separate methods. Those methods which measure overall blood-flow changes in the skin showed increased flow after irradiation at both wavelengths. A method which measured flow only in the superficial vessels showed a slight increase in flow after low doses of both wavelengths, but in contrast, after higher doses, this method showed a marked reduction in flow through the upper dermal vessels. This reduction in flow is probably due to stasis in these superficial vessels, perhaps secondary to vascular damage. Contrary to previous reports, blood-flow changes after irradiation at 250 and 300 nm are similar and may be mediated by identical mechanisms.


Phototoxic blisters from high frusemide dosage. Blistering of exposed areas has appeared in patients suffering from chronic renal failure treated with high doses of frusemide. The blistering, which resembles that occurring in nalidixic acid phototoxicity and in porphyria cutanea tarda, is considered phototoxic in nature.


Effect of the Hewitt keratinizing epidermal carcinoma on cell proliferation in different organs of the host mouse and in human psoriatic skin cultured in diffusion chambers. Incorporation of 3H-thymidine into different squamous epithelia and other tissues was studied in mice bearing the Hewitt keratinizing epidermal carcinoma with a raised epidermal chalone content in the body. The results showed that DNA synthesis in the tumour-bearing mice was inhibited strongly in the epithelium of the ear (c.80%), moderately in the epithelium of the back skin and the foot (c.55%), and weakly in the epithelium of the tongue and the cornea (c.25%). These inhibitions appear to be specific in nature, because cell proliferation was not detectably affected in the sebaceous gland, intestinal epithelium, bone marrow, and thymus lymphocytes. Thymus size, however, was reduced in the tumour-bearing mice compared with controls, and 3H-thymidine uptake was depressed in the spleen and to some extent also in the lymph nodes, possibly owing to non-specific stress. Labelling index of human psoriatic epidermis was suppressed in diffusion-chamber cultures carried by the tumour-bearing host mice compared with controls. However, this reaction was probably not specific in nature, because the labelling index of mouse bone-marrow cells was also decreased when grown in tumour-bearing animals.


In vitro lymphocyte stimulation by wart antigen in man. The lymphocyte transformation test was used to study cell-mediated immunity to wart antigen in patients with active wart infections, in patients with past history of warts and in control subjects. A common pattern was established with wart antigen; a control baseline, followed by a rise of 14C thymidine uptake in the 'active' group and a further elevation in the 'past history' group. Five patients with active warts were followed up and re-examined at various intervals after successful wart resolution; all except one responded to wart antigen by increased DNA synthetic activity after the wart resolution. This increased response was specific for wart antigen and could still be detected 6 months after wart resolution.


Subcutaneous phycomycosis in Uganda.

Subcutaneous phycomycosis in Uganda. This paper reports a further eighty cases of subcutaneous phycomycosis infection in Uganda seen between 1967 and 1974. This brings the number of reported cases from this country to over 140 and indicates an unusual frequency. The infection is more common in certain northern areas but does not appear to be confined to one ecological area. Suggestions are made as to possible factors in the initiation of this unusual infection.


The effect of clobetasone butyrate and other topical steroids on skin thickness of the domestic pig. A new glucocorticoid, clobetasone butyrate, has been shown in patients to have good topical anti-inflammatory activity and a minimal effect on hypothalamic-pituitary-adrenal function. Among a group of topically active corticosteroids, compared in a controlled study in the domestic pig, clobetasone butyrate is shown to cause less epidermal thinning than any of the others except only 1% hydrocortisone. This evidence of a lesser atrophogenic effect may indicate further dissociation of unwanted from wanted properties in clobetasone butyrate.


Cell division and metabolic activity of naevus cells. The relationships between anatomy and behaviour in moles. Thirty moles have been studied by in vitro techniques employing tritiated precursor compounds in order to demonstrate replicative and metabolic activity in naevus cells. Autoradiographs prepared from the incubated tissue showed that replicative activity occurred at all anatomical levels within the naevi. Synthesis of macro-molecules also occurred throughout the mole, but more actively in the junctional and superficial zones. The term 'Junctional Activity' does not appear to have any meaning in cell kinetic terms, and is not associated with any proliferative capacity.


Primary amyloidosis and myelomatosis associated with excessive fibrinolytic acitivty. A case of primary amyloidosis is described in association with Bence-Jones myeloma and increased fibrinolytic activity. Epsilon aminocaproic acid reversed the fibrinolytic activity and clinical improvement was maintained with melphalan and prednisolone.


Clobetasol propionate ointment compared with dithranol in Lassar's paste in the treatment of psoriasis. The initial results on ten patients in a trial of clobetasol propionate (Dermovate) ointment compared with dithranol in Lassar's paste are described. The rates of clearing for each preparation in each patient were not noticeably different. Relapse was slower with clobetasol propionate in all but one patient for whom there was no preference. The results are highly significant (P less than 0-005).


Experimentally induced steroid atrophy in the domestic pig and man. A histological method of ranking topical steroid preparations according to the degree of epidermal thinning they cause in pig skin has been shown to be applicable to human skin. A 0-05% ointment of the new compound, clobetasone butyrate (Molivate), has been shown to cause less thinning than either fluocinolone acetonide 0-025% (Synalar) or flurandrenolone 0-0125% (Haelan) when applied without the use of occlusive dressings for 3 weeks to the human forearm.


Steroid-induced atrophy in an animal and human model. A ratchet-controlled micrometer screw gauge has been used to measure the changes in skin thickness produced by topical corticosteroids. Measurable thinning of the mouse ear followed repeated daily application of corticosteroids. This response in the animal was used to assess the atrophic potential in a variety of standard formulations. The same compounds were applied to human skin and the changes in thickness measured. Patterns of response and the rank order of thinning obtained from the animal model were found to parallel closely the human results.


The pharmacological properties of corticosteroids in relation to clinical efficacy. The pharmacological properties of cortisol (and cortisol-like drugs) are divided into several distinct activities according to the type and cellular site of action of the hormone. To each of these discrete properties is allotted the separate clinical beneficial responses and the adverse effects that probably arise from them. For any one patient only one, or two, of these pharmacological properties are desirable and the remainder are undesirable. Therapy aims to separate the wanted from unwanted effects and this can be attempted in three ways: firstly, by adjustment of dose, frequency and duration of corticosteroid administration; secondly by delivery of the drug directly only to the site of disease--if this is possible; and thirdly, by using analogues which have been synthesized with 'tailor-made' selective actions. Synthetic analogues have not yet offered much selectivity of action of value for systemic use, but for local use (as on the skin and in the respiratory tract) such analogues have provided a considerable therapeutic advance. It is suggested that the several distinctive pharmacological properties of cortisol (as well as the existence of other steroids closely related chemically but with widely different biological activities, such as progestagens and anaesthetics) offer hope for the synthesis of cortisol-like compounds with much greater selectivity in systemic action.


Acute tolerance to effects of topical glucocorticosteroids. Tachyphylaxis (acute tolerance) to two important actions of topical glucocorticosteroids is demonstrated. In humans, topically active glucocorticoids applied to the skin cause vasoconstriction initially but this response fades with successive applications. In hairless mouse epidermis, inhibition of DNA synthesis and mitosis is caused by one application of a glucocorticoid but with repeated administration of the drug this effect is lost. The degree of inhibition of cell division appears to be similar 30 and 54 h after one application of steroid to that following three or five applications during such a time period. These findings suggest that an optimum therapeutic approach to the use of these agents exists.


Steroid structure and steroid activity.

Steroid structure and steroid activity. The diverse biological effects associated with naturally occurring steroids are reviewed, with particular reference to the effect upon biological activity of changes in chemical structure. The motives for synthetic modification of the natural products are discussed and are illustrated by reference to the development of systemic and topical anti-inflammatory agents, with improved potency and reduced side-effects.


The effect of percutaneously absorbed steroids on hypothalamic--pituitary--adrenal function after intensive use in in-patients. Hypothalamic-pituitary-adrenal (HPA) axis function has been monitored in adults and children who required intensive treatment of their skin disease with topical corticosteroid preparations while in hospital. Evidence of mild suppression of the HPA axis was seen in adults when the more potent topical steroids were used, but recovery of function was rapid when the intensive treatment ceased. In children suppression was still present in twelve of sixteen cases on the 2nd day after treatment with 0-1% betamethasone 17-valerate ointment had stopped, yet in nine cases treated in a comparable manner with 1% hydrocortisone acetate ointment, there was no evidence of impaired HPA axis function.


Measuring adrenal function in out-patients using topical corticosteroids. A number of studies describing the effects on pituitary adrenal function of topically applied corticosteroids are reviewed. It is concluded that the adrenal function of the majority of out-patients is little affected by treatment with correctly prescribed topical corticosteroids. However, where patients need brief periods of treatment with large quantities of potent topical corticosteroids for extensive disease, clinicians should be aware of the possibility of transient adrenal suppression.


A hypothesis for the increased oxygen affinity in haemoglobin Malmö. Haemoglobin Malmöbeta97His leads to Gln, a high oxygen affinity haemoglobin which causes secondary erythrocytosis, is transmitted in an autosomal dominant manner. A hypothesis accounting for the high oxygen affinity, hyperbolic oxyhaemoglobin dissociation curve, and the relatively normal Bohr effect is presented. The purified abnormal haemoglobin from the present family provided biochemical and functional data for this hypothesis based on the allosteric model proposed by Perutz. Experimental results support the formation of a chemical bond between the -SH proton of the beta93 cysteine and the amide of oxygen of the substituted beta97 glutamine as an explanation for the high oxygen affinity of haemoglobin Malmö.


Lack of association between the HL-A system and pernicious anaemia. Fifty-two patients with pernicious anaemia have been typed for the histocompatibility antigens. No association was found with any particular antigen.


Relationship between paraprotein polymerization and clinical features in IgA myeloma. The clinical manifestation fo IgA multiple myeloma are usually not considered distinguishable from those of IgG myeloma despite the fact that IgA differs from IgG in several characteristics, particularly molecular size heterogeneity. The clinical and laboratory features of 25 patients with IgA myeloma seen during a 5 year period are presented. The degree of paraprotein polymerization was observed to vary greatly in these patients but remained chronologically constant in six individuals studied on several occasions over this period. The patients were divided into two groups on the basis of the degree of paraprotein polymerization. The first group comprised those patients in whom the IgA paraprotein was greater than 50% polymerized, whilst in the second group the paraprotein was predominantly monomeric. No clinical or pathological differences were seen between the 'polymeric' and 'monomeric' groups of myeloma apart from that directly attributable to the physicochemical effect of the paraprotein polymerization. Thus, five patients out of 11 of the 'polymeric' group had developed the hyperviscosity syndrome, whilst no patients in the 'monomeric' group had developed this complication. The concentration of the paraprotein during the course of the disease was comparable in both groups. This syndrome is considered to be relatively common in IgA myeloma and adds to the morbidity and mortality of the disease. Its anticipation and treatment may improve the quality and survival of patients likely to develop this complication.


Physiology and ultrastructure of the blood platelet following exposure to hydrogen peroxide. Hydrogen peroxide in micromolar concentrations can induce shape change in human blood platelets, and can modify the aggregation and release reaction of these cells as induced by ADP or thrombin. In larger (millimolar) concentrations, H2O2 produces fusion of platelets with distortions in platelet morphology unlike those normally caused by aggregating agents. The production of H2O2 in vivo by granulocytes or other cells could influence the processes of haemostasis or thrombosis.


A standardized bioassay for platelet factor 3 released by kaolin. The test for platelet factor 3 described by Hardisty & Hutton (1975) has been modified to conform to the usual design for a parallel-line bioassay. Manchester Comparative Thromboplastin has been used as assay Standard, allowing an arbitrary unit of activity to be adopted. However, experiments suggested that the platelet activity measured was different from tissue factor activity. Platelets are tested as platelet-rich plasma diluted in a standardized mixture of plasma and fibrinogen, so that differences between the clotting factors of the test samples are eliminated, as verified by experiments on haemophiliacs and patients on anticoagulant treatment. Sonication and repeated freezing and thawing of platelet-rich plasma showed that approximately 15% of the PF3 is released by kaolin. In vivo, a single dose of 600 mg of aspirin reduced the PR3-release to half the previous value in 2 h; initial values were regained in 5-8 days.


Chloramphenicol induced inhibition of platelet protein synthesis: in vitro and in vivo studies. Chloramphenicol (CAP), an antibiotic which causes various blood dyscrasias, was shown to inhibit in vitro protein synthesis of human blood platelets. The effect is dose- and time-dependent, it is reversible after incubation for 2 h, and is comparable with the suppression achieved by cycloheximide (CXM). Electron microscopic examination revealed swelling and destruction of mitochondria. Administration of CAP to dogs produced a progressive inhibition of platelet protein synthesis as shown by a reduction in the rate of [3H]leucine incorporation into protein. The maximal inhibitory effect of the antibiotic was reached 0.5-4.0 h after its administration, when minimal leucine incorporation values of 9-40% of the control were measured. The suppressive effect of CAP was followed by an overshoot in the incorporation of [3H]leucine, up to a maximum of 602% of the value at zero time of the experiment.


In vivo behaviour of homologous urea-soluble 131I-fibrin and 125I-fibrinogen in rabbits: the effect of fibrinolysis inhibition. The in vivo behaviour of urea-soluble fibrin monomer (FM) was compared with that of fibrinogen in rabbits. Purified rabbit 125I-fibrinogen was injected into 36 unanaesthetized rabbits. Three days later the rabbits received either purified rabbit 131I-FM I mg/kg body weight, which corresponds to cI% of the circulating plasma fibrinogen pool 131I-fibrinogen, or buffered urea only. The distribution volume of FM was 43.4 +/- 6.9 ml/kg and of fibrinogen 43.5 +/- 7.7 ml/kg (mean +/- SD). The elimination curve of urea-soluble FM as represented by the clottable 131I-radioactivity. plotted on a semi-logarithmic paper, consisted of an initial steep decay within the first 6 h and a slow flattening of the slope 6 to 24 h after injection of FM. Although a terminal single-exponential slope, as observed in fibrinogen elimination, could not be computed for the 24 h following FM injection the mean half-life time of the last segment of the clottable-radioactivity curve, between 12 h and 24 h, was 12 h. Within 24 h a mean of 83-5% of the injected FM were removed from the circulating blood. The elimination characteristics of fibrinogen were not influenced by the injected FM. Control experiments showed that buffered 3.0 M urea, the solvent of FM, does not influence distribution volume and elimination of 125I-fibrinogen. The distribution of 131I as well as 125I-radioactivities in organs representing FM and fibrinogen respectively did not differ from each other. Elevated levels of 131I-radioactivity, however, were found in the urine after FM injection suggesting an accelerated elimination of FM in comparison to fibrinogen. Fibrinolysis inhibition with high doses of aprotinin did not significantly reduce the urinary excretion of 131I-radioactivity representing breakdown of FM. Furthermore, inhibition of the fibrinolytic system had no influence on the elimination characteristics of either fibrinogen or FM. In order to explain the results obtained in this study the following theory is proposed. Intravenously injected FM forms complexes with fibrinogen and fibrinolytic degradation products. The complexes continuously increase in size until they dissociate into fibrin oligomers and carrier proteins. The oligomers are eliminated whereas the carrier proteins recycle.


Comparison of the coagulant activities of platelets and phospholipids. The coagulant activities of various phospholipid preparations were compared with those of platelets. Folch phospholipid with maximal platelet factor 3 (PF3) activity produced long recalcified clotting times of relatively undiluted plasma in plastic tubes whereas untreated or ADP-treated platelets with minimal PF3 activity produced short clotting times in the same test system which is sensitive to activators of the contact system of intrinsic coagulation. Bell and Alton phospholipids with maximal PF3 activity produced recalcified clotting times similar to those in the presence of platelets. Bell and Alton phospholipids had tissue factor activity, but Folch phospholipid and platelets did not. Bell and Alton phospholipids and gum acacia (used as a vehicle in one of the preparations) activated factor XII as did platelets, but Folch phospholipid did not. The multiple coagulant activities of Bell and Alton phospholipids (i.e. PF3, tissue factor and contact activating) may account for the absence of coagulant superiority of platelets in the undiluted system in plastic tubes. The coagulant activities of platelets are also complex but different from Bell and Alton phospholipids whereas Folch phospholipid would appear to possess only PF3 activity.


Clinical and haematological data in 254 cases of beta-thalassaemia trait in Italy. The haematological and clinical data in 254 Italian subjects with beta-thalassaemia trait are reported. 46% of the patients were anaemic, 40% complained of weakness, 19% showed enlargement of the spleen and 10% enlargement of the liver. The haemoglobin levels ranged from 8 to 15.5 g/dl with a normal distribution and a mean of 12.73 for males, 10.93 for females and 11.34 for children (4-15 years). Reticulocyte counts and serum bilirubin levels were slightly increased and both showed a statistically significant relationship with haemoglobin levels. The serum iron level was increased in 27% and decreased in 6% of the cases. Haemoglobin A2 concentrations ranged from 3.5% to 8% with a normal distribution and a mean of 5.37; Hb F values were less than 1% in 36% and varied from 1 to 14% in the remainder. Red cell osmotic fragility was decreased in all but 6% of the subjects: low MCV, MCH and MCHC values were observed in 75%, 86% and 10% respectively. A comparison is made between the data and those obtained by other workers.


Activation of intravascular coagulation by endotoxin: the significance of granulocytes and platelets. The importance of granulocytes and/or platelets in endotoxin-induced generalized intravascular coagulation was studied as well as thrombocytopenic rabbits. Neutropenia and thrombocytopenia were induced by oral administration of busulphan. Generalized intravascular coagulation, as indicated by renal glomerular microclot formation, was initiated by two intravenous injections of endotoxin. Granulocyte counts before the second injection of endotoxin were most significantly related to activation of intravascular coagulation whereas platelet counts either before the first or second injection of endotoxin were not definitely related to the activation process. Renal glomerular microclots occurred in rabbits after two injections of endotoxin even when the platelet counts were between 500 and 5000/mul. These experiments indicated that granulocytes but not platelets are essential to the activation of endotoxin-induced intravascular coagulation.


A familial abnormality of circulating vitamin B12 binding proteins: occurrence in a family of high serum concentrations of transcobalamin II. A family is described in which two members (a father and a daughter), both with quiescent ulcerative colitis, had abnormally high serum concentrations of a vitamin B12 binding protein. This protein had the molecular weight of transcobalamin II on gel filtration, and behaved like transcobalamin II with respect to its elution from DE-23 cellulose, its inhibition at acid pH, its absorption by uncoated charcoal, its binding by anti-TC II antibodies, and its ability to transfer vitamin B12 to transformed lymphocytes. Its plasma clearance and tissue distribution when injected into rabbits was indistinguishable from that of transcobalamin II from normal subjects. It migrated on electrophoresis in the beta, gamma region. This is the first case report of related subjects in whom high serum concentrations of transcobalamin II have been observed.


Effect of some anticonvulsant drugs on depletion of folate in rats on a vitamin B12-deficient diet. Rats fed on vitamin B12-deficient or vitamin B12-supplemented diets and treated with phenobarbitone by intraperitoneal injection for 5 d showed significant increases in the activity of glutamate formiminotransferase in liver. The only significant depletion in liver folate activity was in vitamin B12-supplemented rats that were starved for 48 h. When rats were given the same diets, with phenobarbitone and diphenylhydantoin added, for 12 weeks or more in two separate experiments, significant increases in transferase activity were found only in the livers of animals fed on the deficient diet. However, there was significant depletion of liver folate in animals taking the supplemented diet.


Rheological properties of red cells in haemoglobin Köln disease. The rheological properties of erythrocytes of four patients with haemoglobin Köln (Hb Köln) disease were studied. Filtration of erythrocytes through polycarbonate sieves with a pore diameter of 5 mum and viscosity measurements of erythrocytes suspensions with a PCV of 80% were carried out. The rheological properties of erythrocytes of two of the patients were severely altered. In both patients an increased haemoglobin attachment to erythrocyte membranes resulting in a decreased filtration rate of erythrocytes was found. One of these cases had been splenectomized some years before. About half of the erythrocytes of this patient contained large Heinz bodies. Erythrocytes of this patient showed a decreased filtration rate and an increased viscosity. Moreover, erythrocytes of healthy adults containing Heinz bodies after incubation with acetylphenylhydrazine showed a decreased filtration rate as well as an increased viscosity. Membranes of erythrocytes of the other patients contained haemoglobin in an amount within the normal range of haemoglobin content of membranes of healthy adults. Erythrocytes of these patients showed normal rheological properties. The haemolytic process in these patients was only mild. We suggest that the amount of total haemoglobin attached to the erythrocyte membrane corresponds to the percentage of the unstable Hb Köln present in the erythrocytes of the particular patient.


The relationship between total red cell volume, plasma volume and venous haematocrit. Total red cell volume (TRCV) and plasma volume (PV) have been measured in 130 cases including 65 polycythaemic patients and 65 patients with a wide variety of disorders. Patients with gross splenomegaly were excluded from the study. The regression of TRCV on venous haematocrit (VHct) was found to be curvilinear, a single exponential function providing a good approximation ( r=0.92, P less than 0.001). No significant difference was found between the mean PVs of the polycythaemic and control groups (40.97 and 42.94 ml/kg respectively) although a slight but highly significant negative correlation was observed between PV and VHct (r = 0.47, P less than 0.001). This most marked for patients with VHcts below 0.30, for whom a separate plot yielded a correlation coefficient of 0.75. Total blood volume (TBV) and VHct were found to be positively correlated (r = 0.57, P less than 0.001) as would be expected from the TRCV and PV data. The significance of these findings is discussed.