Stereospecific biosynthesis of triacylglycerols in mammary glands from lactating rats.

Microsomal plus cytosol preparations from the mammary gland of lactating rats are capable of incorporating palmitic acid and oleic acid into triacylglycerols. These triacylglycerols are similar in structure to those found in rat milk, where palmitic acid tends to be confined to the sn-2-position of the glycerol. Both glycerol 3-phosphate and dihydroxyacetone phosphate function as acyl acceptors. The enzymic synthesis of triacylglycerols appears in late pregnancy, increases rapidly during early lactation, but disappears within 3 days of weaning.


The lipoprotein lipase (clearing-factor lipase) activity of cells isolated from rat cardiac muscle.

The total lipoprotein lipase activity recovered in suspension of cells prepared from adult rat hearts was unaffected by the nutritional state of the animals used. The enzyme activity present in the cell suspensions was almost exclusively associated with the cardiac muscle cells present as the major cell type.


Relation of hemodynamics to the incidence of diethylstilbestrol-induced aortic ruptures in hypertensive and hypotensive lines of turkeys.

Hypertensive and hypotensive lines of turkeys were treated with diethylstilbestrol (DES) alone, or with DES and propranolol (PROP). Untreated turkeys of each blood pressure line served as controls. Mortality rate from aortic ruptures was highest (43.7%) in the hypertensive line treated with DES, but mortality was reduced to 7.7% when this line of turkey was treated with both DES and PROP. Among the hypotensive line of turkeys treated with DES, 26.7% died of aortic ruptures, but none died when these turkeys were treated with DES and PROP. Propranolol did not influence serum cholesterol levels, and all DES or DES and PROP treated birds had greatly elevated values, as contrasted to untreated turkeys. Aortic lipid values were highest in the hypotensive line of turkeys treated with DES, but, by histologic evaluation, aortic atherosclerosis was equally severe in all DES-treated turkeys. Blood pressure and aortic dp/dt max were higher in the hypertensive line treated with DES than in the similarly treated hypotensive line. This probably accounted for the higher mortality in the former group. Absence of significant mortality in either line of turkey following treatment with both DES and PROP apparently resulted from the decreased stress on the aorta caused by lowering of blood pressure and aortic dp/dt max by PROP.


Fatty acids and the initial events of endothelial damage seen by scanning and transmission electron microscopy.

A method was developed for observing changes in the endothelial cells in rabbit ear veins in vivo by scanning electron microscopy. Injection of fatty acids into the ear vein caused damage to the endothelium. The first signs of damage seen were marked bulges in the nuclei and loss of the rhomboidal shape of the endothelial cells. More severe damage included loss of nuclei, leaving holes in the cytoplasm. Some parts of the damaged endothelium showed complete separation of cells from each other and exposure of sub-endothelial tissue to which platelets with pseudopodia were adhering. Damage to the endothelium was produced by arachidonic, linoleic, gamma-linolenic, 8,11,14-eicosatrienoic, 5,8,11,14,-eicosatetraenoic or 15-hydroperoxy-5,8,11,13-eicosatetraenoic acids. The effect of arachidonic acid was not prevented by pre-treating the animals with aspirin. It appears that damage produced by the fatty acids is non-specific.


Pharmacologically induced hypolipidemia. The ethinyl estradiol-treated rat.

The aim of this study was to examine in detail the lipid and apoprotein concentrations in the serum of rats treated with pharmacologic doses (5 mg/kg/d for 5 d) of the synthetic estrogen derivative ethinyl estradiol. The results show that in rats, estrogen-induced hypolipidemia is associated with a nearly complete absence of the lipid and protein moieties normally found in d less than 1.21 fraction of serum. Quantitation of specific apolipoproteins by immunoelectrophoresis show that most apolipoproteins are decreased by more than 90% in the serum of estrogen-treated rats. In contrast to the changes in d less than 1.21 lipoproteins, estrogen treatment only slightly reduced serum phospholipid concentrations (by only 10%) and caused no change in the concentration of serum albumin. The results show that the ethinyl estradiol-treated rat is an excellent model of drug-induced hypolipidemia.


The inhibitory effect of new diphosphonic acids on aortic and kidney calcification in vivo.

Three new diphosphonic acids, i.e. compounds containing a P-C-P bond, have been investigated for their ability to inhibit the vitamin D-induced calcification of aortas and kidneys in rats. The compounds were applied orally in various doses. All of the compounds, which had previously been shown to effectively inhibit the in vitro crystallization of apatite, markedly decreased the amount of calcium deposited in aortas and kidneys. One of the new compounds was substantially more effective than ethane-1-hydroxy-1,1-diphosphonic acid (EHDP), which was used as a reference compound. Diphosphonic acids might be used therapeutically in man against soft tissue calcification.


Effect of carbon monoxide exposure on aortic and coronary intimal morphology in the rabbit. A revaluation.

Non-cholesterol-fed rabbits were exposed to carbon monoxide at concentrations in air of either 200, 2000, or 4000 parts per million (=0.02, 0.2 or 0.4%, vol/vol). Using the same criteria for intimal damage as in earlier morphological studies, no histotoxic effect on intimal/subintimal morphology of coronary arteries or the aorta could be demonstrated, when light-microscopic evaluation was performed blindly.


Endothelial permeability in experimental aneurysms and arteriovenous fistulas in rabbits as demonstrated by the uptake of Evans blue.

Rabbits with chronic experimental arteriovenous fistulas or different types of aneurysm fashioned by microvascular surgery have been examined for changed in endothelial permeability by means of a protein-bound tracer dye technique. The aneurysms and anastomosed veins of the arteriovenous aneurysms exhibited pronounced dye-uptake in contrast to low uptake at sites of sham operation. The results demonstrate the importance of haemodynamic factors in altered endothelial function, as shown with a tracer dye technique in these experimental vascular models.


Effect of garlic on human platelet aggregation in vitro.

In 6 healthy adults the effect of essential oil of garlic on platelet aggregation was studied in vitro with an aggreganometer. The blood was collected in a siliconized centrifuge tube containing sodium citrate. The aggregating agents used were ADP, epinephrine and collagen. In each subject aggregation was studied 3 times: (i) initial fasting control; (ii) immediately after (i) but with essential oil of garlic drawn into the syringe together with the sodium citrate; (iii) 5 days after feeding 0.5 mg of essential oil of garlic daily. Addition of essential oil of garlic inhibited in-vitro platelet aggregation induced by ADP, epinephrine or collagen; the effect was dose-related. Oral administration of garlic also decreased platelet aggregation. Thus, garlic seems to inhibit some aspects of thrombus formation.


Artefacts of localization of atherosclerosis in pinned aortas.

Detailed studies of aortas from 8 rabbits showed that serious artefacts occur if the aortas are pinned at their in vivo dimensions, rather than fixed at physiological pressure. In the pinned aortas, the proximal parts of the branches were pulled up onto the aortic wall. This was more pronounced for the large branches of the abdominal aorta than for the smaller intercostal branches. This artefact caused atherosclerotic lesions, which had developed at the origin of the branch, to appear as if they were entirely on the aortic wall. We found that a marked change in the elastin pattern was present at the origin of the branch; this can be used to mark the true origin of the branch. With the pressure technique we found that lesions had different shapes and locations at different branch points.


The effect of garri on rat plasma cholesterol.

Plasma cholesterol concentrations were measured in rats after incorporation of garri in their diet; control animals were fed a diet without garri. Cholesterol concentrations decreased with incorporation of garri in the diet, but a saturation point was reached after which garri had no further lowering effect on plasma cholesterol. Histology of the kidney and liver revealed cellular vacuolation and cytoplasmic swelling in garri-fed animals.


Significance of luminal plasma layer resistance in arterial wall oxygen supply.

Previous analyses of the arterial wall oxygen supply system have assumed that a cell-free layer of plasma next to the endothelium is the major transport barrier in the lumen. Using a computer simulation, we have quantitatively tested this assumption. Our results show that oxygen diffusion gradients extend significantly into the flowing blood well beyond any plasma layer and that the major luminal transport resistance lies in the flowing blood and not in the plasma layer. The simulation was also employed to compute the effect of a reported 50% drop in plasma oxygen diffusivity. This rather large reduction did significantly lower oxygen levels within the arterial wall tissue. Whether such large reductions in diffusivity ever actually occur in human plasma is a subject of current controversy.


Intravenous fat tolerance in obese Africans with varying grades of carbohydrate tolerance.

An intravenous fat tolerance test (IVFTT) was performed and fasting plasma lipid values determined in 12 healthy normal weight, 18 obese non-diabetic, 9 obese chemical diabetic and 10 obese symptomatic diabetic African subjects. Their insulin responses to an oral glucose load were also determined. Mean plasma triglyceride levels were similar in the normal weight and obese non-diabetic groups but were significantly raised in the two diabetic groups, being highest in the symptomatic diabetics. The fractional removal-rate of an intravenous injection of the fat emulsion Intralipid was significantly less in each of the obese diabetic groups compared with the normal weight or obese non-diabetic group. There was a significant negative correlation in all but the symptomatic diabetic group between the fasting triglyceride level and the rate constants for the IVFTT. These results suggest that the rate of triglyceride clearance is an important determinant of the basal plasma triglyceride concentration in urban African subjects.


Computer assisted tomography and pneumoencephalography in nonhydrocephalic, nontumorous head enlargement.

Forty children with enlarged heads were studied by pneumoencephalography and/or computer assisted tomography (CAT). Ventricular dimensions from CAT scans of 70 normal children formed a control group. In the group of 40 children with neither hydrocephalus nor brain tumor, CAT more reliably showed ventricular enlargement in patients with neurologic impairment.


Asymmetries of the cerebral hemispheres on computed tomograms.

Numerous cerebral asymmetries are shown on cerebral computed tomography (CT). Those seen most commonly are: (a) the left occipital pole is frequently wider and protrudes further posteriorly than the right; (b) the right frontal area often measures wider than the left, and the right frontal pole usually protrudes either as far forward as the left or extends beyond the left; and (c) the calcified glomus of the left lateral ventricle commonly lies posterior to that of the right when there is posterior protrusion of the left occipital pole beyond the right. The above hemispheral asymmetries are more common in right handed individuals. Hemispheral asymmetries tend to be less striking in left handed individuals, but widening of the left frontal and right occipital regions is more common in left handers than right handers. In both right and left handers, the central portion of the right hemisphere is frequently wider than the left; the pineal therefore often lies slightly to the left of the midline in normal brains. A study of cerebral asymmetries should help in the detection of early mass lesions and may also help in the study of hemispheral specialization for behavioral function.


[Sib cases of Dandy-Walker syndrome (author's transl)].

Two children of normal parents had "Dandy-Walker syndrome" (cystic dilatation of the 4th ventricle with incomplete development of the cerebeller vermis). Both cases were admitted to our hospital in neonatal period, because of apneic spell. Air study showed the enlargement of the 4th ventricle in both cases. One case (22 days after birth, male infant) was operated by occipital craniotomy, and cystic membrane of the roof of the 4th ventricle was removed. But his head was growing rapidly in size, which suggested hydrocephalus. He died of pneumonia at 70 days after V-P shunt operation. At autopsy, defect of the cerebellar vermis and tonsil, involving the enlargement of the 4th ventricle was found. Another case, younger sister of the previous one, was complicated by occipital meningocele, which did not communicated with ventricular system. Her occipital tumor was removed, and now, she is growing normally in body size, but does not react to the visual stimuli with considerable psychomotor retardation. In our cases, occlusion of the foramina Luschka and Magendie was not present. So, we have come to the conclusion that primary underdevelopment of the cerebellum is of major importance for understanding of the etiopathogenesis of this syndrome.


[A regional cerebral blood flow in patients with acute subarachnoid hemorrhage--with special references to spasm (author's transl)].

Measurements of the regional cerebral blood flow (rCBF) were performed 44 times on patients with subarachnoid hemorrhage, using the 133-Xe clearance method with aid of the 8 channel detector unit. The patients consisted of 31 preoperative cases within 3 weeks of the last subarachnoid hemorrhage. The sites of the ruptured aneurysms included 11 anterior communicating arteries, 8 middle cerebral arteries, 7 internal carotid arteries and 3 anterior cerebral arteries. In 2 cases, the aneurysms were not identified with the cerebral angiograms. The purpose of this study was to investigate the effect of spasm on the rCBF. The subjects were divided into two groups: those with and without spasm. Furthermore, the group with spasm was divided into three subgroups according to the degree of spasm. The findings obtained were as follows; The group with spasm showed a statistically significant decrease in the mean of the rCBF. The MrCBF was not influenced by the distribution of spasm, however. In the group without spasm, the MrCBF had a good correlation with the cerebrospinal fluid pressure (CSF-P) or the level of consciousness. In the group with spasm, there was no correlation between the MrCBF and the CSF-P or the level of consciousness. For example that marked reduction of the MrCBF were seen in some cases with low CSF-P or only slight disturbance of consciousness. The rCBF was measured 2 or 3 times in 5 cases with spasm. The decrease in MrCBF occured about one week after the incidence of the subarachnoid hemorrhage but MrCBF recovered with the disappearance of spasm 2 or 3 weeks after the attack. There was a poor correlation between spasm and relative flow patterns. The good correlation, however, was found in only one case with the severe spasm at the middle cerebral artery.


[Surgery of anterior communicating artery aneurysm--from the experiences of 346 cases (author's transl)].

In the past 14 years, 1000 cases of aneurysms were submitted to surgical operations without using microscope. In this report 346 cases of anterior communicating artery aneurysms were studied. The operative result at discharge was as follows; 19 cases (5.5%) were dead, 27 poor, 39 fair, 64 good and 197 excellent. In the follow-up, out of 300 cases 29 were dead (16 were related to the operation), 7 were poor, 13 fair, 26 good and 226 excellent. Out of 19 dead cases during hospitalization, 14 were operated within two weeks after SAH. Ten out of 14 cases operated within two weeks died due to vasospasm and all these 10 cases were operated between five to 11 days after SAH. These results and results of ultra-early surgery on other sites of aneurysm suggested that the surgery should be avoided on the cases from third to 10th day after SAH. After the 3rd day, the operation should be decided by taking vasospasm into consideration. If the SAH attack is a mojor one accompanying loss of consciousness more than one hour, the operation should be postponed until the 14th day. If the SAH attack is a moderate one accompanying loss of consciousness within one hour, it should be postponed until the 9th or 10th day. When the SAH attack doesn't accompany loss of consciousness, the surgery can be done any time. If stiff neck is obvious, it should be performed on the 9th or 10th day. Our approach for anterior communicating artery aneurysms is a interhemispherical approach following the bifrontal craniotomy. Hypothermic anesthesia around 27 degrees C was used in order to prolong the temporary occlusion time until 1971. Since 1972, 500 approximately 800 ml of 20% mannitol was applied intravenously for preventing the infarction following the temporary occlusion under the normothermic general anesthesia. Details of the operative records of 346 cases were analyzed and our operative method, technique and technical points were discussed.


[Experimental brain tumors produced transplacentally by ethylnitrosourea (IV): ultrastructure studied by using transmission and scanning electron microscope (author's transl)].

The fine structure of rat gliomas induced transplacentally with a single i.p. dose of 50 mg/kg of Ethylnitrosourea has been studied by using transmission and scanning electron microscope. The subependymal matrix layers of the fetus which was affected by ENU have showed irregular and rough arrangements with expanded extracellular spaces as compared with that of control rats. The cells of subependymal layer seemed to form the microtumor. A so-called "microtumor", which was found in a 8 week old, has been composed of small round cells. The fine structures of these cells have showed the characteristics in primitive oligodendroglioma. The characteristics of the fine structure of astrocytoma cells was identified by both TEM and SEM. The fine structure of subependymal glioma cells was often pleomorphic. These gliomas contained a mixture of primitive oligodendrocytes and ependymal cells together with anaplastic glial cells. With increasing size, the glioma has become more pleomorphic with a mixture of neoplastic oligodendrocytes, astrocytes and ependymal cells, and ependymoma like cells have showed neither cilia nor junctional complex. Abnormal vascular structure in the tumor has been reconfirmed by injection replica scanning electron microscope method. The fine structure of the separated single tumor cell surface was also studied by scanning electron microscope. The differences of the cells surface between that of astrocytoma cell and oligodendroglioma cells were clearly noticed.


[Diabetes insipidus in children--long-term follow-up study].

A follow-up study was carried out on 12 children with vasopressin sensitive diabetes insipidus. 1) Nine cases (75%) of 12 were finally diagnosed as having brain tumor in later course. There were 3 cases (25%) who could not be decided as having brain tumor during the follow-up period of more than 6 years. 2) There was one case who developed the overt signs of brain tumor 9 years after the onset of diabetes insipidus. Therefore, it seems necessary to follow-up cases with diabetes insipidus for at least 10 years before determining it as idiopathic type. 3) In cases with diabetes insipidus due to brain tumor, associated growth retardation, autonomic symptoms, behavior disorder, endocrine dysfunction and metabolic dysfunction were frequently observed. In the case where these symptoms become aggravated with lapse of time, these findings should be taken seriously as indicating brain tumor. 4) In the case showing either anterior or posterior focal slow waves in the EEG, if such focal slow waves aggravate with age, the findings should be considered as indicative of brain tumor. 5) We would like to emphasize the significance of brain tumor as the underlying pathology of childhood diabetes insipidus.


Gaps in anterograde conduction in patients with the short PR interval, normal QRS complex syndrome.

Of 8 patients with the short PR interval, normal QRS complex syndrome studied recently, 3 reported here displayed gaps in anterograde conduction. Atrial premature beats at decreasing coupling intervals conducted with minimal AH prolongation until a zone within the cardiac cycle was reached where conduction failed at a supra-Hisian level. Conduction resumed at earlier atrial coupling intervals and was associated with a sudden increase in the AH interval and the appearance of atrial echo beats with earliest atrial activation on the proximal coronary sinus electrogram. It is suggested that the failure of anterograde conduction at relatively late atrial coupling intervals was caused by a short AH functional refractoriness produced by the pre-excitation of the lower AV junction by a partial AV nodal bypass. Conduction resumed only when early atrial premature beats found the extranodal pathway refractory and were transmitted with decremental delay through the AV node.


Re-entrant tachycardia using two bypass tracts and excluding AV node in short PR interval, normal QRS syndrome.

In patients with the short PR interval, normal QRS complex syndrome, paroxysmal tachycardias are usually the result of circus movement involving the AV node and a partial or complete AV nodal bypass. We report 2 patients with this syndrome who suffered distressing rapid paroxysms of tachycardia but in whom there was evidence of a concealed direct VA connection. In both patients, tachycardia was initiated with critical AV prolongation distal to the His bundle, in response to programmed atrial premature stimuli. The constancy of the timing of the atrial echo from the onset of the QRS complex in the presence of a varying HV interval is evidence for involvement of the ventricles in the re-entry pathway. In addition, in both patients the appearance of left bundle-branch block during tachycardia was associated with appropriate prolongation of tachycardia cycle length consistent with the presence of a direct VA connection. The short AH interval during tachycardia and the absence of critical AH prolongation suggests the participation of a rapidly conducting pathway in the anterograde limb of the tachycardia circuit.


Congestive heart failure in normotensive man. Haemodynamics, renin, and angiotensin II blockade.

The role of the renin angiotensin system was evaluated in 18 normotensive patients with chronic congestive heart failure and in 5 controls. No correlation was observed between plasma renin activity and cardiac index. There was a significant inverse correlation between renin and pulmonary capillary wedge pressure (r = -0.61, P less than 0.01). Renin values of the patients appeared to be increased when compared with controls with similar left ventricular filling pressure. Specific angiotensin II inhibition by saralasin decreased arterial pressure in 8 out of 14 patients: their renin was significantly higher than that of the remaining 6 patients (P less than 0.01). The 2 patients with the lowest renin levels responded to saralasin with a blood pressure increase. Left ventricular filling pressure decreased in all but these latter 2 patients with either little change or an increase in stroke volume. Thus, renin levels appear to be increased in normotensive patients with congestive heart failure when related to left ventricular filling pressure. Renin via angiotensin II plays a role in the blood pressure control of many patients with congestive heart failure. In some patients angiotensin II blockade appears to improve cardiac function by unloading the left ventricle.


Use of amiodarone in bradycardia-tachycardia syndrome.

Five patients with the bradycardia-tachycardia syndrome have been treated successfully with the antiarrhythmic agent amiodarone. Three patients were treated for over nine months and one of these patients had corneal micro deposits. One patient had to be taken off the drug because of side effects. Amiodarone should be tried in patients suffering from the bradycardia-tachycardia syndrome before resorting to cardiac pacing.


Disappearing His deflection. Electrophysiological evidence for conduction defect within the His bundle.

A change in the voltage and character of the His bundle deflection following premature atrial stimuli was observed and analysed in 5 of 95 patients having intracardiac conduction studies because of AV conduction disturbances. Of these 5 patients, 3 had spontaneous block within the His bundle, 2 of them showing block in other segments of the conduction system. With increasing prematurity of programmed atrial stimuli, there was a progressive decrease in the voltage of the His deflection, followed by a split His deflection, and finally disappearance of the His deflection. The voltage of the His deflection was also reduced in sinus beats following spontaneous His bundle premature beats. Similarly, during atrial stimulation at increasing rates, the His deflection decreased in voltage, split, and finally disappeared, but when Wenckebach periods appeared the His deflection reappeared in the first paced beat after the dropped beat. The preceding H-H interval was the only electrophysiological variable consistently related to the changes in the His deflection. These changes in His deflection can be explained electrophysiologically as the result of a conduction disturbance within the His bundle. The clinical significance of the phenomenon is discussed. The occurrence of this phenomenon during a conduction study makes it difficult or even impossible to localise the AV block precisely.


Left anterior hemiblock masking coronary insufficiency.

A case is presented in which transient left anterior hemiblock masked the electrocardiographic signs of coronary insufficiency during work.


Supravalvular aortic stenosis in a twin.

A case of subvalvular aortic stenosis in one of a set of dissimilar twins is reported. The case is discussed in terms of the aetiological factors involved and supports the view that supravalvular aortic stenosis is not environmental and may be genetic in origin.


Cardiac effects of tricyclic antidepressant medication. A preliminary study of nortriptyline.

Systolic time intervals and drug plasma concentrations have been measured in a group of patients receiving repeated treatment with nortriptyline. Significant positive correlations between plasma nortriptyline levels and prolongation of pre-ejection phase (P less than 0.005)) and increase in the ratio pre-ejection phase, left ventricular ejection time (P less than 0.05) were obtained. A deterioration in cardiac function, with increase in heart rate, resulting in a negative inotropic effect has been shown to occur with therapeutic doses of nortriptyline. The potential dangers of tricyclic antidepressant drugs on the heart in patients whose myocardium is already compromised or those who accumulate high plasma concentrations are emphasised.


Application of an improved intracardiac fibreoptic system.

An improved fibreoptic in vivo haemoreflection system has been used in over 200 patients. Continuous recording of oxygen saturation while moving the catheter permits measurement of simultaneous pressure and oxygen saturation at almost an unlimited number of sites through the right heart. The oxygen saturation can be continuously monitored and the response is sufficiently fast to permit investigation of changes in oxygen saturation during portions of the cardiac cycle. Dye dilution curves have been recorded from over 200 patients. The only blood withdrawn for the dye dilution curve was the 3 ml needed for checking the calibration of the instrument. We have found that the calibration is extremely stable. In some instances where it has been deemed impractical to obtain blood for calibration, the calibration factor for each catheter may be used. In any case, the calibration check is performed at the end of the study and does not present problems of sterility. The calibration factor may yield a correction factor which then applies uniformly to all the cardiac output values obtained during the study.


Right ventricular monophasic action potentials in patients with long QT syndrome.

In 3 patients with the long QT syndrome, one caused by quinidine and 2 of congenital origin, right ventricular monophasic action potentials were excessively prolonged and of varying shapes in different recording sites. In addition, effective refractory periods of the ventricular muscle were abnormally long.


Anomalous muscle bundle of the right ventricle. Its recognition and surgical treatment.

This communication presents our experience with 14 cases of congenital heart disease associated with anomalous muscle bundle inside the right ventricular cavity dividing it into two chambers. The clinical picture, natural history, and diagnostic characteristics are described. It can be diagnosed by right ventricular cineangiogram in the anteroposterior position. It can be resected surgically, safely.


Postoperative responses in 'prepared' child after cardiac surgery.

Postoperative reactions of children and adolescents realistically prepared for cardiac surgery were analysed for acute and long-term responses. No cases of delirium or psychoses occurred in the 60 children while they were in hospital. Fifty sets of parents and children answered questionnaires 6 months to 4 years after operation (36 under 1 year, 8 from 1 to 3 years, and 6 over 3 years) and assessment of these showed only long-term reaction. Evaluation of reactions is presented by age and in detail. The children aged 2 to 7 years had the greatest number of negative reactions and the only long-term reaction also came from this group. Children 8 to 11 years of age had the least number of negative reactions and the highest number of positive gains. Adolescents, 12 to 19 years of age, were often concerned with their body image (wanted to be considered 'well', resented the scar, etc). From the standpoint of emotional stability and after effects, the 8 to 11-year-old group seemed to do best.


Aortic regurgitation as a manifestation of giant cell arteritis.

The detailed clinical findings of a 65-year-old woman who developed aortic regurgitation caused by giant cell aortitis are presented. The initial phase of the disease was dominated by severe non-specific constitutional symptomatology suggesting infective endocarditis or a malignancy. Aortic regurgitation as a manifestation of giant cell arteritis has hitherto recieved scant attention in the published reports. The clinical and therapeutic relevance of this masquerade is discussed.


Cardiac and respiratory standstill during sleep.

An obese man, with an attack of myocardial ischaemia, developed arrhythmias only when he was asleep. Episodes of sinus bradycardia occurred progressing to arterioventricular block and sinus arrest. These changes in the cardiac rhythm coincided with periods of sleep apnoea.


The diagnosis of a non-stenotic bicuspid aortic valve.

Follow-up of a group of subjects in whom an aortic ejection sound was the only abnormal finding revealed a bicuspid aortic valve at necropsy or operation in 6 cases. High speed echophonocardiographic studies in 15 subjects with aortic stenosis and known to have bicuspid valves, showed the ejection sound to be exactly synchronous with final halting of the opening aortic valve cusps. Echocardiographic visualisation of the aortic valve from the apex, looking up the left ventricular outflow tract, showed valve echoes during systole indicating abnormal cusp configuration. This proved a more sensitive indicator of a bicuspid aortic valve than the finding of an eccentric aortic valve closure line. These findings were used to evaluate 37 subjects with the auscultatory finding of an isolated aortic ejection sound and the diagnosis of a non-stenotic bicuspid aortic valve was confirmed in 30. The usual cause of misdiagnosis was a sound associated with late tricuspid valve closure. The auscultatory finding of an aortic ejection sound, in the absence of other signs of aortic stenosis, indicates a non-stenotic, bicuspid aortic valve. Confirmation of aortic valvar origin of the sound can be provided by a simultaneous echophonocardiogram.


The natural history of a non-stenotic bicuspid aortic valve.

Forty-one patients in whom the diagnosis of a non-stenotic bicuspid aortic valve had been established by noninvasive techniques were followed up for a mean of 10.9 years. During this period, 2 patients required aortic valve replacement because of the development of calcific aortic valve stenosis at the ages of 52 and 64 and 5 others developed evidence of mild aortic valve stenosis. The appearance of calcium in a bicuspid aortic valve suggests the possibility of subsequent calcific aortic stenosis, and patients with this feature should be carefully followed up. Bacterial endocarditis on the aortic valve occurred in 3 patients, one of whom developed severe aortic regurgitation and subsequently died. Patients with a bicuspid aortic valve are at definite risk from bacterial endocarditis and should receive appropriate antibiotic prophylaxis. In 26/41 (63%) patients there was no clinical change during the follow-up period, including 7 of the patients over the age of 50.


Effect of aortic valvular regurgitation upon the impedance cardiogram.

The first derivative thoracic impedance cardiogram, phonocardiogram, and electrocardiogram were recorded in three groups of 22 subjects each. In Group 1 (control), simultaneous impedance cardiogram, phonocardiogram, and aortic valve echocardiograms showed that the X point of the impedance cardiogram occurred synchronously with the aortic second heart sound and with echocardiographic aortic valve closure. In group 2 (clinical diagnosis of aortic regurgitation) the scalar magnitude of the impedance cardiogram O wave and the ratios of the impedance cardiogram wave form X/dz/dtmax and O/dz/dtmax were different from control. In addition, the early diastolic (X) and systolic portions (S) of the impedance cardiogram wave form of group 3 patients were planimetered and expressed as the ratio X/S, called the impedance cardiographic aortic regurgitant fraction (aortic RFI). The aortic RFI was increased by handgrip, a manoeuvre which acutely increases the magnitude of aortic regurgitation. The difference between Fick cardiac output and left ventricular angiographic output was used to calculate aortic valvular regurgitant fraction, which related closely to the impedance cardiogram. These data suggest that it is useful in the noninvasive assessment of aortic regurgitation.


Renal arteriovenous fistula masquerading as severe valvar heart disease.

Two patients with renal arteriovenous fistulae are described, who presented in high output failure. Murmurs were detected in these patients on routine physical examination years before, and when cardiac failure ensued they were assumed to have decompensated valvar heart disease. Full investigation revealed the arteriovenous fistulae and both patients made a good recovery after surgical ligation.


Diagnosis of coronary artery disease by estimation of coronary sinus lactate.

In an attempt to assess the value of coronary sinus lactate estimation before and during atrial pacing for the diagnosis of obstructive coronary artery disease, 70 patients with angina were investigated in this way and by selective coronary arteriography. Thirty-five had radiologically normal coronary arteries and 35 had coronary artery disease. When the change in coronary arteriovenous lactate difference was less than 0.09 mmol/l (0.8 mg/100 ml) between the control and the peak atrial pacing sample, the coronary arteries were normal except in one patient who had distal disease of a single vessel. When the change was greater than 0.22 mmol/l (2.0 mg/100 ml) coronary artery disease was always found, and when the change was greater than 0.39 mmol/l (3.5 mg/100 ml) there was always disease of two or three vessels. Unfortunately, the presence or absence of coronary artery disease could not be predicted when the change fell between 0.09 and 0.22 mmol/l (0.8 and 2.0 mg/100 ml). Estimation of coronary sinus lactate before and during atrial pacing can thus frequently distinguish patients with normal coronary arteries from those with coronary artery disease.


Comparison of interventricular septal motion studied by ventriculography and echocardiography in patients with atrial septal defect.

Abnormal systolic interventricular septal motion is an echocardiographic manifestation of right ventricular volume overload. In order to determine the anatomical basis for this echocardiographic finding, septal motion recorded by left lateral or left anterior oblique ventriculograms was compared with echocardiography ventricular septal motion. Thirteen patients with secundum atrial septal defects and 7 control patients with trivial or no heart disease were included in the study. We found that on ventriculograms the systolic motion of the interventricular septum was similar in both atrial septal defect and control patients. That is, the cephalic third of the septum moved anteriorly in systole in 9 of the 13 patients with atrial septal defect and in 3 of the 7 controls. The caudal two-thirds of the septum moved posteriorly in all patients. These results are compatible with the theory that argues that the echocardiographic abnormalities of septal motion in patients with atrial septal defect result from an end-diastolic septal flattening or bowing of the septum into the cavity of the left ventricle.


Effects of halothane and sodium thiopentone on surface brain pressure and brain electrical impedance in dogs with normal intracranial tension.

The effects of the inhalation of halothane and the i.v. administration of thiopentone on surface brain pressure and brain electrical impedance, at a frequency of 1 kHz, were investigated in 14 chronically implanted dogs. In dogs with normal PaCO2, halothane, at inspired concentrations of 0.8, 1.2, 1.5 and 2.0%, produced increases in brain pressure and impedance. Thiopentone i.v. and hyperventilation preceding the administration of halothane lessened, but did not prevent, the increases in brain pressure and impedance. Thiopentone 35 mg kg-1 decreased both pressure and impedance. The dose-related (P less than 0.01) increase in surface brain pressure was attributed to cerebral vascular expansion; the increase in impedance was not dose related and was interpreted as a loss of conductivity in brain extracellular space (e.c.s.). This loss could be a result of a decrease in both brain e.c.s. volume and its electrolyte concentration resulting from intracellular translocation and electrical inactivation of available ions in brain e.c.s. caused by increased cation binding. These phenomena might be related to the interaction between the anaesthetic molecule and cell proteins. The present study suggests that, in contrast to thiopentone, halothane induced a reversible ionic imbalance in the central nervous system.


A chemical adsorption system for the sampling of gaseous organic pollutants in operating theatre atmospheres.

The development of an air sampler and its use in measuring organic pollutants in operating theatre atmospheres are described. Air was sampled continuously during an operating session and the results obtained represent the average pollution at the sample site during that session. The technique involved the chemical adsorption of organic vapours to polymer beads and pollutants thus trapped could be stored for several days before thermal desorption and analysis by gas chromatography. The three most abundant organic pollutants were ethanol, propan-2-ol (isopropanol) and halothane.


Nitrous oxide contamination in dental surgeries using relative analgesia.

The concentrations of nitrous oxide were determined at various positions in four dental surgeries in which nitrous oxide sedation was used without scavenging. Contamination was present in all the surgeries, the greatest concentration being recorded at the dentist's nose and the least in the peripheral air. The reception area adjoining the surgeries was found also to be contaminated by nitrous oxide.


The negative pressure relief valve: pressure-flow relationships.

The scavenging of gases from anaesthetic circuits may present hazards to the patient. The negative pressure relief valve prevents the generation of subatmospheric pressures in the circuit as a result of a discrepancy between the fresh gas flow and the gas evacuation rate. The ideal valve will open at a small negative pressure, and immediately permit a high gas inflow. Leakage with positive pressure in the circuit and admixture of atmospheric air during spontaneous respiration must not occur. Six different valves were studied. Two membrane valves came nearest to fulfilling the ideal requirements.


Death attributable to anaesthesia. A 10-year survey (1967--1976).

The mortality associated with 240 483 anaesthetics administered over 10 years at Groote Schuur Hospital, Cape Town, is reported. The frequency of death to which anaesthesia contributed was 0.22 per 1000 anaesthetics (compared with 0.33 per 1000 in the previous 10 years). These deaths were responsible for 2.2% of the total mortality from surgery. Two-thirds of the "anaesthetic" deaths were attributable to (in order of frequency): (a) hypovolaemia; (b) respiratory inadequacy following myoneural blockade; (c) complications of tracheal intubation; (d) inadequate postoperative care and supervision.


Cerebral blood flow and metabolism during etomidate anaesthesia in man.

The effects of etomidate on regional cerebral blood flow (rc.b.f.) and cerebral metabolic rate for oxygen (CMRo2) were studied in seven patients undergoing diagnostic carotid angiography. Following determination of baseline rc.b.f. while awake, the patients were anaesthetized with a single dose of etomidate 15 mg. Thereafter, an infusion of etomidate (2 or 3 mg min-1) was administered. Etomidate decreased both rc.b.f.10 (mean decrease 34%) and CMRo2 (mean decrease 45%). It was concluded that etomidate is a potent cerebral metabolic depressant. Furthermore, the cerebrovascular reactivity to carbon dioxide was maintained under etomidate anaesthesia.


Serum thyroid hormones changes in patients undergoing Caesarean section under general or regional anaesthesia.

The effects of anaesthesia on serum thyroid hormones were studied in 32 pregnant young women undergoing Caesarean section at term. Eighteen patients received general anaesthesia and 14 lumbar extradural blockade. Maternal serum concentrations of thyrotrophin (TSH), thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) were measured using radioimmunoassay at 0, delivery and 24 h. There were no significant changes in TSH in the two groups. T4 concentrations decreased significantly at 24 h in the general anaesthesia group but regional anaesthesia produced a significant decrease only at the time of delivery. T3 concentrations decreased with both techniques. Reverse T3 increased markedly with general anaesthesia only at 24 h.


Clearance of neostigmine from the circulation during the antagonism of neuromuscular block.

The plasma concentration of neostigmine was measured in five patients during the antagonism of neuromuscular block. The concentration of the drug decreased rapidly between 2 and 5 min after administration, and then more slowly. Detectable concentrations of neostigmine were present in plasma after 60 min. In the five patients the distribution half-life of neostigmine was less than 1 min; the elimination half-life ranged from 15.4 to 30.1 min.


Antagonism of neuromuscular block by physostigmine in man.

In 20 adult patients undergoing inguinal herniorrhaphy neuromuscular block was induced with tubocurarine 10 mg. In 10 patients, neostigmine 1--2 mg antagonized the block and restored the twitch response to its baseline value. Physostigmine, up to 4 mg, did not produce significant antagonism of the neuromuscular block.


Potency of mixtures of general anaesthetic agents.

The anaesthetic potencies of binary mixtures of the gases argon (Ar), nitrous oxide (N2O) and sulphur hexafluoride (SF6) have been measured using mice. The mixtures SF6-N2O and N2O-Ar showed additive behaviour, whereas the constituents of the mixture SF6-Ar were non-additive, having a smaller total potency than expected. Further experiments on this mixture with Italian Great Newts and on the carbon tetrafluoride mixtures CF4-Ar and CF4-SF6 with mice suggested that the anomalous potencies may arise from specific pulmonary effects associated with the breathing of SF6 accompanied by a high pressure of some other gas.


Comparison of active and passive manoeuvres on the pattern of airway closure in man.

The effect of active and passive manoeuvres on closing volume was studied in conscious subjects. There were no significant differences in closing volume in nine of 10 non-smokers. There was a significantly greater closing volume with the passive manoeuvre (airway pressure +3 kPa to --2 kPa) in seven of nine smokers and one non-smoker with evidence of mild obstructive airway disease. The sensitivity of the closing volume to airway pressure could not be reproduced in three non-smokers exposed to a histamine aerosol. In two of three smokers the effect of airway pressure on closing volume was abolished by salbutamol. The results suggest that subjects with irritable airways may show an increase in closing volume with a change in airway pressure.


Effect of thiamylal on the sensitivity of glycerinated cardiac fibres to calcium.

Clarification of the mechanisms of the myocardial depression produced by thiamylal was sought by studying the effect of thiamylal upon the sensitivity of contractile proteins to calcium (Ca2+), by using glycerinated muscle fibres from the canine right ventricle. The dose--response relationship between the concentration of Ca2+ and the force of contraction of the glycerinated cardiac muscle fibres was not shifted from the control curve by the administration of thiamylal 67 microgram ml-1. This result suggests that the changes in the sensitivity of contractile proteins to Ca2+ are not responsible for the depression of myocardial performance produced by thiamylal.


Effects of age and sex on ketamine anaesthesia in the rat.

Intraperitoneal injections of ketamine 75 mg kg-1 in rats of both sexes (age 1--16 weeks) revealed a significant relationship between increased age and decreased duration of sleeping time for both sexes during the first 3 weeks of age. This decrease in sleeping time seemed to be associated with the increased production of the cyclohexanone oxidation metabolite of ketamine. After 3 weeks of age there was a greater sleeping time in the female rat than the male and this seemed to be associated with a greater ability of the male to produce the cyclohexanone oxidation metabolite.


Effects of althesin and ketamine on resting and stress stimulated adrenocortical activity in rats.

The effects were studied of two i.v. anaesthetics (Althesin and ketamine) on resting and activated adrenocortical function in the rat. Small doses of Althesin and ketamine comparable to those required to produce induction of anaesthesia in man evoked adrenocortical stimulation, but the stressing effects of ketamine were more prolonged. During deep anaesthesia with either anaesthetic there was an inhibition of pituitary adrenal activation induced by handling and surgery. However, during recovery, ketamine was associated with intense and prolonged adrenocortical stimulation. The stress of laparotomy in control rats and in rats pretreated with the anaesthetics caused a depletion of noradrenaline in the hypothalamus; this suggests that both anaesthetics inhibit adrenocortical activation by mechanisms different from adrenergic inhibition.


Effects of halothane on glucose metabolism after injury in the rat.

The effects of halothane anaesthesia on glucose metabolism have been investigated in rats after a non-lethal scald injury. Anaesthesia was induced about 70 min after injury. Glucose metabolism was studied at two stages: during and shortly after induction, and about 2 h after induction. Comparisons were made with conscious rats at the corresponding times after injury. All rats were in an ambient temperature of 30 degrees C. During and shortly after the induction of anaesthesia, halothane caused a rapid increase in plasma glucose concentration, which by 30 min had begun to return to the values in injured controls; thus glucose production and utilization were increased. Insulin concentrations were increased also. However, after 2 h exposure halothane had decreased glucose production and utilization, as determined with [5-3H]- and [U-14C]-glucose, increased plasma concentrations of insulin and decreased liver concentrations of glycogen, that is it had exacerbated well-known effects of injury in the rat, including insulin resistance. Hyperglycaemia was not increased.


Arterial dominance in the hand.

Arterial pressure was measured simultaneously in the thumb and in the contralateral arm using strain-gauge plethysmography in 100 healthy persons aged 13--43 yr, before and after compression of the radial or the ulnar artery. The radial and ulnar pulses were palpable in all instances. In 29 (14.5%) hands compression of either artery did not reduce the thumb pressure. In 152 (76%) occlusion of the radial artery caused a decrease of more than 10 mm Hg, but never to less than 40 mm Hg. In 91 (45.5%) occlusion of the ulnar artery reduced thumb pressure, on three occasions to less than 40 mm Hg. Radial dominance was shown in 110 hands (55.0%), 24 (12.0%) showed ulnar dominance and in 66 (33.0%) neither vessel dominated.


Frequency of previous anaesthesia in an anaesthetic patient population.

Ten thousand patients presenting for anaesthesia were questioned about their anaesthetic history; 6672 had received an anaesthetic previously, 19.2% in the preceding 4 weeks. Of 2780 in whom the agents were known, 80.4% had received thiopentone, 18.1% Althesin and 57.4% halothane. Thirty-seven per cent of the total survey population had received two or more anaesthetics.


Evaluation of three preparations of etomidate.

Three formulations of etomidate were evaluated in unpremedicated patients undergoing minor gynaecological procedures. There was a high frequency of pain on injection (up to 50%) and excitatory phenomena (up to 95%) with all formulations. The frequency of excitatory phenomena was significantly greater than that after methohexitone. Recovery was rapid, but emetic sequelae were frequent and significantly more marked than after methohexitone.


Changes in plasma concentration of adrenaline and noradrenaline in anaesthetized patients during sodium nitroprusside-induced hypotension.

Changes in plasma concentrations of adrenaline and noradrenaline were measured when sodium nitroprusside (SNP) was used for the induction of hypotension in healthy adults undergoing middle ear surgery (group 1) and patients undergoing neurosurgery for subarachnoid haemorrhage (group 2). The mean catecholamine concentrations before the infusion of SNP were four to five times greater in group 2 than in group 1. Group 1 showed significant increases in plasma catecholamines during hypotension induced with SNP, the increase correlating significantly with the degree of hypotension and the rate of infusion of SNP. Group 1 showed an increase in heart rate of about 10%, which could not be related to the catecholamine concentrations. In group 2, changes in plasma catecholamines following infusion of SNP were inconsistent. This may have been because the sympatho--adrenal medullary system was already maximally active and was unable to respond further to induced hypotension.


Plasmapheresis and plasma cholinesterase.

Plasma cholinesterase (E.C. 3.1.1.8) concentrations were measured in nine outpatients who were undergoing regular plasmapheresis. A single plasmapheresis produced a 64% reduction in cholinesterase concentration compared with the value before plasmaphersis. Another patient who received four plasma exchanges in 6 days showed a progressive reduction in cholinesterase concentration to only 8% of the initial value. It is suggested that drugs metabolized by cholinesterase should be used with caution in patients undergoing plasmapheresis, particularly when frequent plasma exchanges are undertaken.


Changes in ionized calcium and other plasma constituents associated with cardiopulmonary bypass.

Plasma concentrations of calcium fractions, proteins, phosphate and magnesium were measured before, during and after cardiopulmonary bypass in 15 patients undergoing cardiac surgery. When calcium chloride was added to a pump priming solution which contained little or no blood, the concentrations of all calcium fractions were significantly greater after bypass than before, with a mean ionized calcium concentration of 1.52 mmol litre-1 plasma water, 30 min after completion of bypass. This iatrogenic hypercalcaemia was increased significantly by the administration of more than 10 mg kg-1 calcium chloride in the first 30 min after bypass. Other plasma constituents showed the dilutional effect of the pump prime during bypass and only the magnesium concentration failed to return towards normal values after operation.


Tracheal tubes and connectors used in neonates--dimensions and resistance to breathing.

The dimensions of tracheal tubes and connectors in common use were measured together with the resistance to breathing at flow rates occurring in babies breathing quietly. The outside diameters of rubber tubes varied more than those of plastic tubes. The main factors influencing resistance were the internal diameter and a sudden change in diameter or direction of flow. These are of particular importance in tubes of 2.5 mm i.d. and less and may cause an increase in the work of breathing during spontaneous ventilation. The resistance of small Cole pattern tubes was greater than that of plain tubes of similar o.d.


Application of the Doppler ultrasound bloodflow detector in supraclavicular brachial plexus block.

A Doppler ultrasound bloodflow detector was used to localize the third division of the subclavian artery, rendering the supraclavicular approach to the brachial plexus safer and highly successful.


Emergency obstetric anaesthesia and the use of beta2-sympathomimetic drugs.

A case of severe foetal distress is recorded and the rationale and use of a beta-sympathomimetic drug are described.


Enhancement and metastasis after immunotherapy of ovine squamous-cell carcinoma.

Extracts of ovine squamous-cell carcinoma (OSCC) prepared by different procedures, were injected at varying concentrations into 184 tumour-bearing sheep. At a total protein of 0.5 mg and greater, there was significant enhancement and metastasis in all 120 sheep examined. Extracts of OSCC containing less than 0.5 mg protein, or of human squamous-cell carcinoma and normal sheep skin containing high levels of protein, had no effect on subsequent tumour development. Extracts of foetal sheep skin at the 3mg-protein level produced significant enhancement and metastasis. The degree of enhancement was inversely proportional to the developmental stage of the tumour at the time of treatment.


Evaluation of the normal-lymphocyte-transfer test.

The normal-lymphocyte-transfer test has been advocated as a method of assessing the immuno-competence of lymphocytes from patients with breast and large-bowel cancer. Evidence is presented in this paper that the methodology is subject to many uncontrollable errors, that the reaction is the result of multiple factors, and that the size of the reaction is related to the age of the patient and not to the extent of the malignancy.


Effect of lymphocyte supernatants on the electrophoretic mobility of erythrocytes: significance in cancer diagnosis.

We have determined that when an extract of human brain is preincubated with lymphocytes its subsequent capacity to inhibit the electrophoretic mobility of tanned and stabilized erythrocytes is much reduced. There is a differential effect, however, as the observed reduction is from 73% inhibition to approximately 35% when the pre-incubation is with lymphocytes from patients with malignant disease, but from 73% to approximately 10% when it is with lymphocytes from normal controls. These values were obtained at a brain extract concentration of 333 microgram/ml, with 5 times 10(6) lymphocytes, a pre-incubation time of 18-24 h, and a temperature of 27 degrees C, which are the optimum conditions determined for differentiation between cancer patients and normal subjects. In a series of 73 subjects tested by this method 43/51 cancer patients gave an unequivocal "positive" value, 22/22 normal controls gave a "negative" value, with no false positives.


Oncogenic transformation in vitro by the hypoxic cell sensitizer misonidazole.

The hypoxic cell sensitizer Misonidazole (Ro-07-0582) induces oncogenic transformations in the C3H/10T1/2 mouse embryo cell line cultured in vitro. A drug concentration of 0.4 mM applied to aerated cells for 3 or 6 days results in a transformation rate comparable to that observed following an X-ray dose of 1 Gray. A higher drug concentration of 6.0 mM is equivalent to 4 Gy. The combination of Misonidazole and X-rays produces a significant increase in the frequency of transformation over either drug or radiation alone, but the data are equivocal on the question of additivity vs synergism.


Potentially carcinogenic analogues of the carcinogen hexamethylphosphoramide: evaluation in vitro.

Experiments conducted in vitro are described which indicate that a family of specifically substituted phosphoramides may share the carcinogenic properties displayed by the structurally novel carcinogen, hexamethylphosphoramide (HMPA). Most of the analogues tested only gave a positive response in vitro when using a substantially modified liver homogenate activation system (S-9 mix). The analogy drawn in our earlier paper between this new class of potential carcinogens and the nitrosamine carcinogens, has been strengthened. The following compounds gave a positive response in the cell transformation assay of Styles: hexamethylphosphoramide (HMPA), hexamethylphosphorous triamide, hexamethylphosphorothioic triamide, tripiperidinophosphine oxide, phosphorothioic trimorpholide and diethoxymorpholinophosphine oxide (DEMPA).


Measurement of oestradiol receptors by five institutions on common tissue samples.

The soluble oestrogen-receptor content of common breast tumours has been measured by 5 different laboratories, each using their own assay procedure. Good agreement was achieved on whether a sample was positive or negative for oestrogen receptor. Qualitative differences between laboratories could be explained by differences in thiol-reagent content of assay medium and by the method of homogenization. Recommendations are made on some of the factors involved in the routine assay of receptors in breast tumours.


Oestrogen receptors and the response to endocrine therapy in advanced breast cancer.

The relationship between oestrogen-receptor protein (ER) content of the tumour and the response to endocrine therapy was determined in 119 patients, in a collaborative prospective study. Twenty-eight of the 80 patients with measurable ER responded to treatment according to UICC criteria, compared with only 3/39 without ER. It was found that site of biopsy did not influence the result, but tumour content of the tissue sample was significantly related to the presence of receptors. The organizational problems of such a study are discussed.


Bone-metastasizing renal tumour of childhood.

A primary renal tumour of childhood with histological appearances different from the nephroblastoma is described. This neoplasm, predominantly seen in boys, has a tendency to metastasize to bone. Such metastases are considered to be rare in nephroblastoma and this aspect in studies of Wilms' tumour series is thought to be due, for the most part, to the inclusion of a particular bone-metastasizing tumour in the material.


Incidence and long term survival of children with intracranial tumours treated in Denmark 1935-1959.

The total number of children under 15 years of age with intracranial tumours in Denmark during the years 1935-1959 was found to be 533. The average incidence was 21 new cases/10(6) children/year during the 25-year period in question, and 25/10(6) children/year during the first 17 years of Danish cancer registration. The sex ratio (290 boys to 243 girls) was not significantly different from that of the child population in Denmark. In 219 cases the tumour was located in the supratentorial and in 314 in the infratentorial space. 93% of the tumours were histologically verified, with the following order of frequency for the most usual types: astrocytomas (all grades), medulloblastomas, ependymomas, and craniopharyngiomas. Follow-up was 100%. For the 345 children who survived for more than one month after operation or diagnosis, 36% were alive after 15 years. 119 patients were alive in April 1974 and these were all observed between 15-40 years after diagnosis and operation. Of these 44 had tumours in the supratentorial and 75 in the infratentorial space. 66% of the survivors with supratentorial and 90% with infratentorial tumours led a normal life. Most of the survivors had had a cerebellar astrocytoma, a supratentorial astrocytoma, an apendymoma or oligodendroglioma, but other histological diagnoses were also represented, especially in the supratentorial group. The long-term prognosis was especially bad for children with brain-stem tumours, infratentorial ependymomas and medulloblastomas.


Experimental paracoccidioidomycosis: cranial and nasal localization in mice.

An experimental mouse model for paracoccidioidomycosis (South American blastomycosis) is described. When distribution of cranial lesions following i.v. injection was investigated, invasion of the nasal mucosa with subsequent discharge of budding Paracoccidioides brasiliensis cells into the nasal cavity was noted. The possible significance of this finding in terms of the processes associated with naturally occurring paracoccidioidomycosis is discussed.


Sensitivity to pyrexial temperatures: a factor contributing to virulence differences between two clones of influenza virus.

The influence of pyrexia on the differential persistence of a virulent and an attenuated clone of influenza virus in the respiratory tract of ferrets has been further studied. Clone 64d, an attenuated clone of a recombinant virus (A/PR/8/34-A/England/939/69 (H3N2)) grown in organ cultures of ferret nasal turbinates, was inactivated at pyrexial temperatures more readily than a virulent Clone 7a. In addition, replication of Clone 64d was restricted at pyrexial temperatures to a greater extent than that of Clone 7a in organ cultures of both ferret nasal turbinate and lung tissue. The greater adverse effects of pyrexial temperatures on Clone 64d appears to explain the earlier reduction of upper respiratory tract infection seen in ferrets infected with this attenuated clone. Also, the differential influence of pyrexial temperatures may be the reason for the virtual lack of lung infection with Clone 64d in vivo in contrast to the consistent infection found with Clone 7a. The relevance of these findings to human infection and to markers of attenuation of influenza virus is discussed.


Use of lysostaphin to remove cell-adherent staphylococci during in vitro assays of phagocyte function.

Lysostaphin, a bacteriolytic enzyme, has been used to remove cell-adherent and extracellular Staphylococcus aureus from phagocyte-bacterial mixtures in vitro. Lysostaphin kills S. aureus more rapidly than penicillin, is not toxic for phagocytic cells and, when used for short periods at low concentrations, appears to enter neither human nor mouse mononuclear phagocytes. The use of lysostaphin provides the basis of a simple reliable direct in vitro assay for measuring the attachment and ingestion of S. aureus by phagocytic cells.


The effects of changes in diet on lipid levels and platelet thrombus formation in living blood vessels.

The work reported here describes an in vivo study over several days in each animal, of the formation and behaviour of platelet thrombi in injured living blood vessels in response to topically applied adenosine diphosphate (ADP) in rabbits fed initially on normal diets, then on experimental "saturated" or "polyunsaturated" diets. The effects of these diets on triglyceride fatty acids and on cholesterol and triglyceride levels are reported. It may be of significance that in each experiment the "polyunsaturated" and "saturated" diets appeared to be associated with an increased sensitivity to ADP greater than observed in rabbits on a normal diet or in normal animals in other studies.


The morphology of alveolar tissue destruction.

Destruction of intra-alveolar stroma in regions of tuberculous pneumonia is described. This destruction is associated with phagocytosis of argentophilic granules and fibre fragments by macrophages. The specific features of stromal destruction consist of sequestration, fragmentation, lysis, and other, less obvious, changes in reticulin and collagen fibres found in the air spaces. These findings have important implications in chronic fibrosing pneumonitis where similar intra-alveolar stromal changes occur. Destructive stromal changes have also been noted within granulomatous nodules of sarcoidosis in the region of giant cells. Some of the latter also contain argentophilic fibre fragments.


A morphological study of the effects of 5-hydroxytryptamine and indomethacin on rat mesenteric venules.

A method is described for preparing venules of the rat mesentery for electron microscopy after the application of 5-hydroxytryptamine (5-HT) and pretreatment with indomethacin. Local application of 5-HT caused the leakage of colloidal carbon and the emigration of leucocytes into the venule wall. 5-HT also caused endothelial cells to bulge and their nuclei to contort. It increased the number of protrusions on both the luminal and abluminal surfaces of the endothelium and increased the width of the subendothelial space, and the degree of vesiculation in the endothelial cells. Systemic treatment with indomethacin significantly decreased the amount of carbon passing through the endothelium after the local application of 5-HT, but enhanced some of the other effects of 5-HT. Thus it increased the bulging of endothelial cells and contortion of their nuclei, and further increased the number of surface protrusions and the subendothelial space. It had no effect on the emigration of leucocytes resulting from the application of 5-HT.


The preparation, properties and action on Staphylococcus aureus of purified fractions from the cationic proteins of rabbit polymorphonuclear leucocytes.

A micropreparative electrophoresis system for purifying the major staphylocidal fractions of cationic proteins from rabbit polymorphonuclear leucocytes is described. The most staphylocidal fraction prepared is also the most cationic and contains two bands migrating immediately behind protamine sulphate on analytical acid gel electrophoresis. SDS gel electrophoresis indicates that these proteins have low molecular weights between 3,500 and 14,400. The staphylocidal activity of the fraction is affected in the same manner as a crude extract of rabbit PMN granules by iron compounds, respiratory inhibitors, and compounds affecting energy transfer and oxidative phosphorylation. It is stable to heating up to 80 degrees and amino acid analysis shows that it contains 24% arginine. Electron microscopy of staphylococcal spheroplasts treated with the purified fraction or with the crude extract shows that they both have a very marked "blebbing" and distorting action on the double membrane. Comparisons are made between the action of the purified fraction and protamine, and it is concluded that they have very similar, although not identical, properties and actions on staphylococci.


Possible role of connective tissue in epidermal neoplasia.

Interactions between epidermal cells have been defined within a proposed mathematical model of mammalian skin. Testing the model in a computer suggests that in highly proliferating conditions of the epidermis competition for cell space in the basal layer may be sufficient to generate considerable forces in the papillary dermis. Data shown from human and pig epidermal hyperplasia indicate that basal cells are submitted to considerable lateral forces and that these and not dermal hyperplasia are the forces responsible for the increasingly folded dermo-epidermal junction. When the model was examined in condition of persistently high mitotic rate it was found that it could remain stable only if new connective tissue synthesis was not induced by the developing papillary tension. This complex and counterproductive relationship that may occur between epidermis and dermis and its possible role in the development of neoplasia are discussed.


Leukocyte migration agarose test (LMAT) in sarcoidosis using Kveim test material.

The two-stage leukocyte migration agarose test (indirect LMAT), shown to be a sensitive in vitro assay for cell-mediated immunity, was used to study Kveim reactivity in vitro in patients with sarcoidosis. No Kveim-induced inhibition of leukocyte migration in agarose or Kveim-induced lymphocyte transformation in vitro was found in 23 patients with sarcoidosis, suggesting that the Kveim reaction is not an expression of cell-mediated immunity.


Toxic epidermal necrolysis. Five case reports of unusual presentation in Zambians.

A new clinical presentation of epidermal necrolytic reaction affectting a limited area is reported in 5 Zambian patients. No definite causative factor could be identified in any of these cases. A staphylococcal aetiology is suspected because of the compatible histological features. However, none of the patients had pyogenic skin lesions and staphylococcus was not isolated from the skin lesion.


Possible defects in triacylglycerol and phosphatidylcholine metabolism in psoriatic epidermis.

Biopsies of normal skin, psoriatic lesions and the adjacent psoriatic skin were incubated with I-14C-acetate, 32P-orthophosphate and U-14C-glycerol. Total incorporation of I-14C-acetate into psoriatic lesions (17 samples) was 50% higher than in the adjacent uninvolved epidermis (9 samples) and 120% higher than into normal epidermis (10 samples). In the psoriatic lesion a much higher proportion of the total incorporation was into the neutral lipids and was due mainly to a very high incorporation of I-14C-acetate into the triacylglycerols. The I-14C-acetate incorporated into the phospholipids and especially phosphatidylcholine was proportionally much less in the psoriatic lesion and uninvolved psoriatic epidermis than in normal epidermis even though the incorporation of 32P-orthophosphate and U-14C-glycerol, both representing de novo synthesis, into the phospholipids in the psoriatic lesions and uninvolved epidermis were higher (four-fold in lesion) than in normal epidermis. Our findings (1) are evidence for a much increased triacylglycerol synthesis in psoriatic epidermis which would account for the long-known observation of lipid droplet accumulation in psoriatic cells; (2) suggest that in psoriatic epidermis there is a defect in phospholipid metabolism mainly involving phosphatidycholine and the deacylation (phospholipase A)-reacylation (phospholipid acyltransferase) cycle for fatty acid transfer.


Glucose tolerance in eczema.

The glucose tolerance of thirty-nine patients with eczema was studied by the intravenous glucose tolerance test. The glucose disappearance rate for the eczema group was 1.69 +/- 0.13 mg % per min and for that controls was 2.92 +/- 0.12, indicating impairment of glucose tolerance in eczema patients.


Oral methoxsalen photochemotherapy of recalcitrant dermatoses of the palms and soles.

PUVA therapy successfully cleared various dermatoses mainly confined to the palms and soles in 18 of 20 patients treated. The conditions treated were: plaque-type psoriasis, pustular psoriasis, endogenous eczema and persistent palmoplantar pustulosis. Seventeen patients were treated in a controlled study of PUVA therapy versus no treatment at all and in 16 of these patients the disease was cleared in the PUVA-treated areas while the untreated areas remained unchanged or deteriorated. Twelve of the 18 patients were maintained in a clear state by continued maintenance PUVA treatment over 6--31 months while 3 patients had a spontaneous remission and are free of disease off all treatment.


Induction of UV light tolerance by PUVA in patients with polymorphous light eruption.

A tan induced by 8-methoxypsoralen-long wave ultraviolet light has proved an effective photoprotective sunscreen in 5 patients with long wave ultraviolet light-induced polymorphic light eruption.


Treatment of pustular psoriasis with clofazimine.

Two cases of generalized pustular psoriasis (von Zumbusch) were successfully treated with clofazimine. No side effects were noted except deep red staining of the skin which faded afterwards.


Assessment of the skin penetration properties of different carrier vehicles for topically applied cortisol.

Four commercially available topical preparations of cortisol, Alphaderm, Calmurid HC, Efcortelan and Topisone, had trace quantities of tritiated cortisol added to them. The resultant radiolabelled creams were applied to the dorsum of the pig and the penetration of the steroid was assessed. Alphaderm was shown to deliver approximately 16.0 times more cortisol to the skin than Topisone, approximately 8.0 times more than Efcortelan and approximately 3.0 times more than Calmurid HC.


Oral treatment of ichthyosis with an aromatic retinoid.

An aromatic retinoid (Ro-10/9359) was used for oral treatment of five cases of ichthyosis (three lamellar, two X-linked. Complete clearing of the skin lesions was achieved in all five patients within 24.2 +/- 3.2 days (X-linked 21.75 +/- 6.5, lamellar 23 days). Histopathology showed reduction of the hyperkeratosis, and thickening of the granular layer. Clinical side effects were of mild intensity and included cheilitis, conjunctivitis and pruritus. All side effects were reversible upon reduction of the daily dosage. In three patients treatment was discontinued after clearing of lesions. Fresh lesions re-appeared 6 weeks later. One patient with X-linked ichthyosis developed two recurrences during maintenance treatment; one patient with lamellar ichthyosis was kept in complete remission for 9 weeks on a reduced daily dosage.


Atopic dermatitis and congenital deafness.

In a family with perceptive, non-progressive hearing loss several of the members suffered from atopic dermatitis. The proband had a severe atopic dermatitis and an extremely high IgE value. Some of the family members suffered from atopic dermatitis, others from deafness, and some from both diseases. The co-existence of these two disorders has been previously described in two families. Atopic dermatitis and perceptive, non-progressive congenital deafness might be genetically associated.


Yellow nail syndrome associated with mental retardation in two siblings.

Two siblings with yellow nail syndrome and mental retardation are described. In addition to nail changes, the younger brother was found to have congenital lymphoedema and idiopathic pleural effusion, and the elder brother, lymphoedema praecox. They had in common a history of respiratory tract infections. Their intelligence quotient as measured by the Suzuki-Binet tests was 30% and 70%, respectively.


Non-inflammatory dermal elastolysis.

A 33-year-old woman is described who suffers from an idiopathic loss of mid-dermal elastic tissue which leads to wrinkling of the skin and to discrete perifollicular protrusions. In accordance with Sheley & Wood (1977) we conclude that these findings represent a new entity for which we propose the term 'non-inflammatory dermal elastolysis'.


Ultraviolet light inhibition of oriented fibrin formation in psoriasis.

Radially-oriented fibrin crystallization was induced by incubation of blood from psoriatic patients with killed Pseudomonas aeruginosa. The phenomenon was inhibited by irradiation of the buffy coat in plasma with UV-B. It was not inhibited by UV-A unless trioxsalen had been added. Addition of UV-A-irradiated plasma to non-irradiated buffy coat also inhibits the fibrin formation.


Mouse screening test for evaluating protection to longwave ultraviolet radiation.

Albino mice photosensitized to psoralens were used for evaluating a sun-barrier preparation for use against longwave ultraviolet radiation. The difference in thickness of the treated and control ears at various times after irradiation was used as a measure of photoprotection.


A comparison of the anatomical uniformity of irradiation in two different photochemotherapy units.

Measurements have been made of the anatomical distribution of ultraviolet radiation resulting from the irradiation of an inanimate manikin in a PUVA 6000 unit and a PUVA 4000 unit. The dosimeter used was phenothiazine film. The results indicated a very similar pattern of relative UV dose on the surface of the manikin from both units.


The effect of a single plunking at different times in the hair cycle on the growth of individual mouse vibrissae.

Mouse vibrissae have been plucked at precise times throughout the hair cycle and the time of appearance of the new hair noted for each individual follicle. It was found that plucking a vibrissa at any time during the cycle resulted in the induction of a new hair and in no case did the follicle continue the same cycle. All the vibrissae grew at the normal rate of 1.0 mm/day for most of the growing period and whenever plucked during this period a new hair appeared after 8--11 days. When the growth rate fell to 0.6--0.7mm/day at the end of the growing period plucking resulted in the appearance of a new hair after 7 days. When the growth rate fell to 0.1--0.3 mm/day a new hair appeared 5 days after plucking, thus the time of normal eruption was not altered. When whiskers were 10--15 mm long and about half way through the active growth phase their follicles were surgically transected at one of three different levels: (1) just above the dermal papilla which left all or most of the differentiating matrix cells, (2) mid-follicle and (3) at the level of the sebacaous gland. In each case the distal part of the hair was then plucked. In five out of ten cases when the cut was made just above the dermal papilla a new hair erupted after a variable time 10--15 days. In all other cases the existing hair cycle was completed after a delay of a few days. This emphasizes the importance of the differentiated matrix cells in the maintenance of the hair cycle.


The long term effect of repeated pluckings on the function of the mouse vibrissal follicles.

Single mouse vibrissae were plucked repeatedly at the same time of the cycle (10--15 days after eruption) for ten successive cycles from eight individual follicles. After three pluckings the first grey whisker appeared, after six pluckings all were grey. Two follicles stopped producing whiskers after seven pluckings and another two after the 8th. Henceforth only 50% of the follicles continued producing whiskers until the end of the experiment. All the follicles which ceased to produce whiskers had a keratogenous cyst occupying most of the follicle in direct contact with the dermal papilla. In all cases the isolated dermal papilla was condensed and rounded in shape. Both loss of pigment and cyst formation could be due to the mechanical damage in the follicle caused by repeated plucking.


Alopecia areata: immunofluorescence and other studies.

In a study of 24 patients with alopecia areata, scalp biopsies were examined for immunofluorescence; all were negative. A number of other tests also failed to confirm an auto-immune aetiology for this disease. A possible explanation lies in the heterogeneity of alopecia areata, only a small proportion of cases being of the auto-immune type.


Leukoderma in the nude C57BL/6 mouse.

The nu gene bred into mice causes the animals to be athymic and nude, that is their hairs do not project past the follicular orifice making them appear to be hairless. The gene has been bred into C57BL/6 mice. C57BL/6 mice which are homozygous for the gene are runted and nude and develop leukoderma around 6 weeks of age. The leukoderma is caused by shedding of short stubby, barely visible black hairs, probably a normal hair cycle. This type of leukoderma is not vitiligo, a disease which causes the skin to turn white because of destruction of the melanocytes in the epidermis or hair bulbs.


Complement components in blood serum and suction blister fluid in erythropoietic protoporphyria.

Complement factor's C3c, C4, factor B, C3d and the immunoglobulin IgA were determined in suction blister fluid of patients with erythropoietic protoporphyria and in normal controls. The levels increased when the skin of the patients had been previously irradiated with 'white light', but with Kromayer radiation, and were interpreted as being the result of increased vasopermeability.


Genital warts: incidence of associated genital infections.

Two hundred and seventy-eight men and 200 women who presented to a Special Treatment Clinic with genital warts were screened for accompanying genital infections. One hundred and twenty-nine of 212 presentations (61%) in women compared to 98 of 303 presentations (32%) in men were accompanied by another genital infection P less than 0.001). Recurrent presentation with warts was commoner in men (P less than 0.001). In both sexes recurrences were less likely to be accompanied by another genital infection. (P less than 0.002). Yeasts (25%), C. vaginale (21%), N.gonorrhoea (12%) and T. vaginalis (12%) were the commonest pathogens in women. Non-specific genital infection (17%) and gonorrhoea (10%) were the commonest accompanying infections in men. The identification and treatment of these infections, especially in women, is important for the rapid eradication of warts, for, by increasing genital moisture they can create and maintain a favourable environment for wart proliferation. In addition to screening all patients with warts for other sexually transmitted diseases, women should be screened for yeasts and C. vaginale.


Failure of metronidazole treatment in Ethiopian mucocutaneous leishmaniasis.

Metronidazole was found to be of no value in the treatment of five cases of Ethtiopian mucocutaneous leishmaniasis.


An hereditary syndrome of lumpy scalp, odd ears and rudimentary nipples.

A syndrome, consisting of a congenital abnormality of the scalp, ears and nipples inherited as an autosomal dominant trait, is reported. Ten affected members of a family over five generations are recorded and the four living affected members are described in detail. A review of congenital localized aplasias of skin suggests that this may be a new syndrome.


Follicular atrophoderma with multiple basal cell carcinomas (Bazex).

Five patients from a single family are reported who have an inherited condition of which the main features are follicular atrophoderma, abnormalities of scalp hair and multiple basal cell carcinomas. Thes abnormalities are consistent with the syndrome described by Bazex et al. (1964). The pattern of inheritance of this condition is discussed.


Co-existence of pemphigus, anti-skeletal muscle antibody and a retroperitoneal paraganglioma.

Occasional reports have appeared in the literature describing a relationship between pemphigus vulgaris and malignancy (Krain & Bierman, 1974; Tagami et al., 1976). Carcinoma of the ovary, stomach, breast, endometrium and bronchus have all been associated with pemphigus (Krain, 1974). The association between pemphigus and thymoma is well known (Stillmand & Baer, 1972). Pemphigus has also been described in connection with various lymphoproliferative malignancies (Naysmith & Hancock, 1976). The purpose of this paper is to describe a patient who suffered from a rare retroperitoneal tumour in association with pemphigus vulgaris. His serum contained a high titre of anti-skeletal muscle antibody, although he showed no clinical manifestations of myasthenia gravis. He also had immunological manifestations suggestive of lupus erythematosus.


Epithelioid sarcoma--a case report.

A case of epithelioid sarcoma is reported which clinically resembled sporotrichosis.


Urticaria-like lesions associated with systemic lupus erythematosus: response to dapsone.

A cases of systemic lupus erythematosus is reported, presenting with urticaria-like lesions and complement deficiencies, which was completely controlled by dapsone.


Psoriasis and occlusive vascular disease.

To test the hypothesis that psoriasis is associated with an increased incidence of occlusive vascular disease (thrombophlebitis, myocardial infarction, pulmonary embolization, and cerebrovascular accident), the clinical records of 323 psoriatic and 325 non-psoriatic patients admitted to the dermatology service of the Roger Williams General Hospital were examined. The data obtained in this study suggest that (1) the occurrence rate of occlusive vascular disease is significantly greater in the psoriatic than in the non-psoriatic dermatological patient. This is particularly true in the male population; (2) psoriasis predisposes to occlusive vascular disease; and (3) the psoriatic patient with certain predisposing factors is at greater risk of experiencing an occlusive vascular episode than both the non-predisposed psoriatic and the non-psoriatic dermatological patient.


HLA antigens in persistent palmoplantar pustulosis and its relationship to psoriasis.

HLA typing was performed on 93 patients with persistent palmoplantar pustulosis. The incidence of either HLA B13 or BW17 was not significantly increased as compared to controls. In addition the frequency of BW35 was no different from controls. However, the present results document a significantly increased frequency (38.7%) of B8. Taken together these data are good evidence that palmoplantar pustulosis is a genetically distinct disease entity from psoriasis vulgaris, despite the increased incidence of psoriasis in the condition.


Multinucleate epidermal cells in non-neoplastic dermatoses.

Multinucleate epidermal cells (MEC) originated from keratinocytes were observed histologically in 92 of 197 cases of non-neoplastic dermatoses, such as lupus erythematosus (26 of 70), lichenoid eruptions (26 of 47), Hailey-Hailey disease (5 of 5), psoriasis vulgaris (20 of 49) and so on. Most of these cells had two nuclei, and a few had three nuclei. MEC usually showed perinuclear bands of eosinophilic material which also showed positive staining for epidermal fibres (tonofilaments). In all cases of Hailey-Hailey disease, close correlation between formation of MEC and dyskeratotic tendency was observed. From these findings, it is concluded that the mechanism of formation of MEC in these dermatoses may be similar to that of Bowen's disease, in which dyskeratotic tonofilaments become entangled with the spindles of the mitotic apparatus so that normal cell division cannot take place. It seems likely that MEC are a manifestation not only of malignant dyskeratosis but also of benign one.


Dermo-epidermal relationships in pyogenic granulomata.

The epidermis of pyogenic granulomata is presented with an unusual problem of distorted dermoepidermal relationships. In this study we have attempted to delineate the problem and have studied the way in which the epidermis copes with its difficulties. Sixteen pyogenic granulomata with (where possible) paralesional skin (and for comparison ten Campbell de Morgan spots) were studied by cell kinetic techniques. High labelling indices were found in the epidermis and in the endothelium in the pyogenic granulomata (contrasting strikingly with the findings in the Campbell de Morgan spots). A variable morphological response was found ranging from hyperplasia with parakeratosis to epidermal thinning and atrophy. Possible mechanisms for the epidermal changes are discussed and it is suggested that the data produced from this and similar studies may aid the understanding of dermo-epidermal interaction in a variety of common skin disorders including psoriasis.


Towards characterization of epidermal cell migration promotion activity in serum.

The effect of various fractions of serum on active epidermal cell migration in vitro has been studied by incubating small explants of normal human skin in the presence of the fractions and determining the extent of migration after 48 h incubation. Serum was fractionated by combining ammonium sulphate precipitation and molecular sieve chromatography using Sephadex G-200. The components of serum responsible for most, if not all, of the migration promotion activity were localized in the G-200 third peak (albumin fraction) of the supernatant after precipitation of the serum with ammonium sulphate at 50% saturation.


A new form of cellular arrangement in guinea-pig ear epidermis.

A new type of squame arrangements is described in guinea-pig ear epidermis. It is characterized by overlapping obliquely-angled outer cells and squames, which thus form a roof-tile pattern. This pattern develops in epidermis that is thicker than about 42 micron; in thinner epidermis the outer cells and squames form the usual columnar stacks. It is concluded that the roof-tile pattern, which is usually directed towards the ear edge, is typical of slight to moderate hyperplasia. In extreme hyperplasia, when the strata granulosum and corneum are destroyed, only cellular disorder is seen.


Human infections with Microsporum persicolor in Denmark.

The geographical and ecological spread of Microsporum persicolor is reviewed. It is concluded that M. persicolor is a zoophilic dermatophyte prevalent mainly in Europe and seldom reported as the cause of human infection. Twelve Danish cases of M. persicolor infection are described--their clinical features, mycological findings, and treatment. The localization of these fungal infections is reviewed on the basis of the present material and 58 cases from the literature.


An assessment of (1) cyproterone acetate and (2) ethinyl oestradiol and lynoestrenol (Minilyn) in the treatment of idiopathic hirsutism.

The administration of cyproterone acetate can be effective in the treatment of 'idiopathic' hirsutism. In 5 similarly affected patients treated with ethinyloestradiol and lynoestrenol (Minilyn) the rate of hair growth was reduced in only two, even though the serum total testosterone was reduced in each instance.


Generalized Hailey-Hailey disease.

A woman of 60 developed a generalized erythroderma. The case history revealed classical symptoms of Hailey-Hailey disease for 17 years. Light- and electron microscopic investigations confirmed the diagnosis of generalized Hailey-Hailey disease--an extremely rare condition. Two additional cases with widespread clinical manifestations are presented. These observations underline the fact that the whole epidermis is genetically disturbed and may react to various insults with suprabasal acantholysis.


Buckley's syndrome.

An infant girl with chronic eczema, recurrent infections, elevated IgE and impaired neutrophil chemotaxis appeared to belong to the group of patients described by Buckley, Wray & Belmaker (1972). An hereditary influence is suggested by a similar defect found in the patient's mother. Levamisole improved the in vitro defect and the clinical picture.


Localized crusting as an artefact.

Four patients are reported, two with gross crusting of the nose and two with gross crusting of the lips considered to be artefacts. The crusting was easily removed using soft paraffin or Viscopaste.


Eruptive melanocytic naevi following severe bullous disease.

Two patients developed eruptive naevi following severe bullous disease. The naevi developed after an interval of months and remain unchanged 4 years later. Eruptive naevi have been described after convulsions and both patients developed bullous disease after treatment for convulsions.


Ways of expressing results of human bone marrow progenitor cell culture.

In human bone marrow culture studies the number of granulocyte progenitor cells (CFUc) is expressed as the number of colonies per 10(5) incubated, nucleated cells. However, this provides little information on cell proliferation kinetics of granulopoiesis. The ratio of progenitors (CFUc) to end cells (metamyelocytes or granulocytes) is related to the effectiveness of granulopoiesis and this allows an estimate to be made of an amplification factor within the maturing and proliferating compartments. We measured an index equal to the number of CFUc per 10(5) falls when a large number of granulocytes is produced by each progenitor cell. This was observed in many patients with a neutropenia. An estimation of the total number of metamyelocytes is based on the ratio of the number of metamyelocytes to the number of blood granulocytes. This allows an estimate of the total number of CFUcs, which is of clinical interest.


A comparison using quantitative enzyme cytochemistry between leucocyte alkaline phosphatase levels in the bone marrow and blood of the rat.

Leucocyte alkaline phosphatase (LAP) levels have been compared in neutrophil polymorphs in bone marrow and blood in the rat, using a quantitative enzyme cytochemical technique. It has been shown that LAP levels are higher in bone marrow than blood, both in normal animals and those with experimentally-induced local inflammatory lesions. In the latter group both marrow and blood LAP levels were higher than in controls; blood levels rose because of the outpouring of cells with moderately high LAP levels into the blood and marrow levels rose because only cells with very high LAP levels remained. The inverse relationship between neutrophil age and alkaline phosphatase content, previously demonstrated in the peripheral blood of the rat, has also been shown to exist in the bone marrow.


Correction of the bleeding time in patients with storage pool deficiency by infusion of cryoprecipitate.

Five patients with Hermansky-Pudlak syndrome: storage pool deficiency, albinism and ceroid containing bone marrow macrophages and three patients with uncomplicated storage pool deficiency were treated with cryoprecipitate from 16 donors. Within 2 h of transfusion, bleeding times decreased towards a third of initial values. This effect lasted for at least 4 h but had disappeared after 24 h. Six of these eight patients were also treated with an equal volume of human albumin solution. Infusion of albumin had no effect on the bleeding times. The abnormal platelet function tests and biochemical abnormalities (decreased values of platelet total adenosine diphosphate (ADP), adenosine triphosphate (ATP(I) and serotonin) remained unchanged. On four occasions infusion of cryoprecipitate twice daily protected patients with Hermansky-Pudlak syndrome and storage pool deficiency from bleeding during surgery. The mechanism of action of cryoprecipitate in this clinical situation is obscure.


Malignant histiocytosis: a clinico-pathological study of 12 cases.

The clinico-pathological features of 12 cases of malignant histiocytosis (histiocytic medullary reticulosis), aged 12-60 years, were studied. Special emphasis was put on the analysis of the haematological, cytological and histopathological findings of the disease. Bone marrow aspirates and biopsies from involved tissues (liver, lymph node, spleen and skin) were found best suited for establishing the diagnosis. Cytochemical and ultrastructural data support the concept that the neoplastic cells belong to the mononuclear-phagocyte system. Three untreated patients died in less than 6 months. Median survival of the nine treated patients was 1 year. Seven patients were treated with the combination chemotherapy CHOP and four achieved a complete remission. Three of them are alive and continue in unmaintained remission for more than 1 year, surviving so far for 18+ to 31+ months. Two cases showed evidence of CNS involvement, one during life and the other as a post-mortem finding. The differential diagnosis from other related or unrelated disorders and the possible aetiological factors responsible for the disease are discussed in detail.


Erythrokinetic studies in myelofibrosis: their significance for prognosis.

Eighty-three patients with myelofibrosis have been studied by erythrokinetics and have been followed up until death or for at least 12 months. Because of a large plasma volume the venous haematocrit gives only a poor idea of the red blood cell volume. The red cell survival was reduced in the majority of cases but significant haemolysis was rare. The amount of haemolysis of autologous and isologous red cells was similar, suggesting an extra-corpuscular origin for the haemolysis. Plasma iron turnover was always increased, sometimes markedly, but red cell iron incorporation was reduced in 70% of cases, indicating ineffective erythropoiesis. Surface counting showed an absence on diminution of sacral iron fixation and a rapid and marked splenic uptake in more than 90% of the cases; uptake of iron by the liver occurred in half the cases, usually not very high; iron release from the spleen was absent or reduced in 67% of the cases. The degree of ineffective erythropoiesis as measured by radio-iron incorporation and release by the spleen, the amount of haemolysis, and the red cell volume were strongly correlated with prognosis. These factors enabled a more precise prediction to be made of the clinical outcome in the 2 years following the study, than the clinical data alone. A prospective study might show whether erythrokinetic studies are also useful in determining the choice of treatment.