Assembly of bacteriophage phi X174: identification of a virion capsid precursor and proposal of a model for the functions of bacteriophage gene products during morphogenesis.

A capsomeric structure sedimenting with an S value of 108 in sucrose gradients was isolated from Escherichia coli infected with bacteriophage phi X174. The 108S material contained viral proteins F, G, H, and D, and the relative amounts of these proteins in the 108S material were similar to those in the infectious 132S particle, which has previously been described as a possible intermediate in the assembly of 114S phage particles. Electron micrographs indicated that the size and shape of the 108S material resemble those of the 132S particle. The 108S material contained no DNA, and its formation occurred independently of DNA synthesis. The 108S material accumulated in infected cells when viral DNA replication was prevented either by mutation in phage genes A or C or by removal of thymidine from a culture infected with wild-type phage or with a lysis gene E mutant. Upon restoration of thymidine to cells infected with the lysis gene E mutant and then starved of thymidine, the accumulated 108S material was converted to 132S particles and to 114S phage particles, implying that the 108S material is a precursor of phage particles. A model that proposes possible functions for the products of phi X174 genes A, B, C, D, F, and G during viral replication and phage maturation is described.


Glucocorticoids and development of audiogenic seizure susceptibility in DBA/1Bg mice.

Metopyrone, an inhibitor of glucocorticoid synthesis, blocks the development of susceptibility to audiogenic seizures in C57BL/6Bg mice after either acoustic priming at 19 days of age or ethanol withdrawal at 70-80 days of age, whereas it has no effect on the development of genetic susceptibility in DBA/1Bg mice. This suggests that there may be similar developmental mechanisms for effects of acoustic priming and ethanol withdrawal on audiogenic seizure risk, which may be different from that for the genetic susceptibility of DBA/1Bg mice.


Study of variations in the male and female glottal wave.

A reflectionless metal tube which can act as a pseudoinfinite termination of the vocal tract was used to collect glottal volume-velocity waveforms produced by 10 male and female adult subjects. From each subject glottal volume-velocity samples were collected of normal, loud, and soft voice; falsetto and creaky voice; monosyllables with rising and failing intonation; and three-syllable utterances containing primary lexical stress on one of the three syllables. Analysis of the data indicates a wide variation of the glottal waveform shape, its rms intensity and fundamental frequency, phase spectrum, and intensity spectrum. It is observed that as the fundamental frequency changes over time, the glottal source varies in one of two different ways. In one type of change, the harmonic relations in the glottal spectrum become steeper as fundamental frequency rises. In a different type of glottal-wave change, relations between harmonics tend to remain the same despite a change in the fundamental frequency; the source spectrum in this case is simply shifted along the frequency and amplitude axes as a function of fundamental frequency. To account for these variations in the glottal source, at least three factors must be known: the sex of the speaker, the voice register in which he phonates, and the linguistic context in which the phonation occurs.


Erythropoietic protoporphyria: juvenile protoporphyrin hepatopathy cirrhosis and death.

Severe hepatic cirrhosis and failure in erythropoietic protoporphyria is rare. An 11-year-old boy is described who developed protoporphyrin hepatopathy (protoporphyrin 5.75 mg/gm liver wet weight), cirrhosis, and liver failure and died.


Plasma hormone levels in normal and lead-treated pregnant mice.

Dietary lead (0.5%) was given to mice which, after mating, exhibited a vaginal plug. Estradiol, progesterone and prostaglandins E and F 2 alpha were determined in the plasma by radioimmuno assay at different times thereafter. The increase in estradiol and decrease in prostaglandins prior implantation are not greatly altered by lead treatment, whereas the subsequent increase in progesterone and later in estradiol is abolished. It is concluded that the lower number of pregnancies seen in lead-treated mothers is due to a maternal hormonal imbalance caused by lead.


[Placental pathology of the small-for-gestational-age newborn infant].

The problem of the newborn that is small for its gestational age is emphasized. Fetal growth is dependent upon the growth potential of the fetus and the availability of intrauterine nutrition. Proper nourishment for optimal fetal growth will require adequate maternal and placental circulations, sufficient quantities of circulating nutrients in the maternal blood, and a proper area of placental membrane, which is capable of achieving satisfactory maternal-fetal transfer. Many factors appear to produce this syndrome including genetic anomalies, intrauterine infection and deficiencies of placenta and cord, but in most small-for-dates infantes the common underlying situation appears to be a state of intrauterine malnutrition, mediated by a maternal-fetal vascular insufficiency. Placental factor probably accounts for only a small proportion of deprived fetuses. However, the present knowledge on the histopathology of the placenta from cases of small-for-date babies is relatively poor to reach a final conclusion. More research in the direction of the maternal side of the placenta and in particular to the placental bed, including more complete study of the lesions in the uteroplacental vessels will probably clarify the problem of fetal growth retardation.


[Study on breast feeding in a suburban area].

Human milk is considered the best nourishment a child can have during his first months of life, providing that it exists in sufficient amount. In a study of the feeding characteristics in suburban areas of Mexico City, it was found that 71 mothers would continue to breast-feed their children up to the twelfth month. Supplemental feeding began during the first four months with: fruit, vegetables, eggs, meat and in final stages, soups and cereals. The great majority of the mothers thought that human milk is the ideal food for their babies. The medical concept about breast-feeding in the suburban areas of Mexico City is mistaken, due to information based on foreign studies contrary to national reality. In spite of the widespread belief that breast-feeding has decreased in frequency, in this study it was found that it is still popular and commonplace. We recommend that through all information sources, the inestimable value of human milk as an ideal nourishment, due to its nutritional, economical, psychological and hygienic properties, should be emphasized.


[Serologic survey for the determination of antibodies against various virus infections, Mycoplasma, beta hemolytic A Streptococcus and Toxoplasma gondii, performed on children of a State-of-Mexico municipality].

A seroepidemiologic inquest was carried out in 667 children from the county of Huixquilucan, Mexico, looking for serum antibodies against infections caused by the following microorganisms: Epstein-Barr virus; cytomegalovirus; syncytial respiratory; para-influenza 1, 2 and 3; measles; rubella; mumps; Mycoplasma pneumoniae, beta hemolytic A Streptococcus and Toxoplasma gondii. The findings are reported. Considerations are made on the incidence of these diseases in different age groups and a comparison is established with the findings in other countries, since there is no previous information in Mexico for some of the viral agents studied.


[Osteopetrosis (report of 2 cases)].

Two distinct and characteristic cases of osteopetrosis are presented. The first concerns a fourth month old baby with the malignant form of the disease, initiated since the newborn period. He was admitted because of abnormal ocular movements and probably deafness. At the physical examination he showed bilateral optic atrophy, abnormal ocular movements, hepatosplenomegaly and petechia. The diagnosis was confirmed by clinical means and radiological studies of virtually all of his skeleton. Several fractures were found. Laboratory tests showed marked anemia, trombocytopenia "tear cells", evidence of medullary erythropoiesis and myelofibrosis. An increased alkaline phosphatase was detected in serum and in granulocytes. The second case corresponds to a 26 year-old female with the benign form of the disease. She had multiple pathological fractures specially of her lower limbs, that produced severe impotence in her gait. In this case, the diagnosis is suspected on clinical basis and confirmed with the characteristic radiological findings. Some of the more distinct features of the disease are discussed, specially those concerning the genetic mode of inheritance and consanguinity, the etiopathogenic, pathophysiology, clinical, laboratory, prognosis and treatment, with particular reference to the radiological and hematologic problems related with this metabolic disorder.


[Lipoid nephrosis in a child with advanced Hodgkin's lymphoma].

This is a case of an eight year old male, with Hodgkin's disease grade IV-B, with initial clinical presentation of nephrotic syndrome. The renal biopsy showed minimal change lesions. He had a complete remission of the nephrotic syndrome and Hodgkin's disease after been given prednisone and chemotherapy respectively. The remission of the nephrotic persisted 22 months and the Hodgkin's disease, 23 months. It has been established that cellular immunity is altered in Hodgkin's disease. The etiopathogenesis of lipoid nephrosis is unknown. There are clinical and experimental evidences showing cellular immunity in patients with lipoid nephrosis, suggesting a possible involvement of this mechanism in the etiopathogenesis of lipoid nephrosis. This could explain a relationship between the nephrotic syndrome (lipoid) and Hodgkin's disease. Our patient, besides Hodgkin's disease, showed clinical, biochemical and histologic changes, as well as clinical course compatible with nephrotic syndrome with minimal changes lesions.


[Early diagnosis of hip dysplasia].

Stress is placed on early diagnosis and treatment of dysplasia of the hip, which should ideally be made at birth. The frequency of this condition with dislocation in babies born at Hospital Infantil de Bogotá was 2.7 per 1,000. The frequency of breech presentation in babies with dysplasia of the hip was 20.2%. The average age at the first consultation for this condition was 24 months. The most important clinical signs for the diagnosis are Barlow's and Ortolani's signs and limitation in abduction of the hip. X-ray studies bear an unquestionable importance in the diagnosis; however, a normal film in the newborn does not discard a clinical diagnosis of dysplasia. Examination of the hips should be a routine in all newborn services in the country. A special regulation in this sense should be set. In this campaign, there should be a joint participation of pediatricians, obstetricians and orthopedists. The pediatrician must control the hips of the child, even if they apparently normal, until walking is initiated. The principles of treatment of dysplasia of the hip in all its varieties are described. The main objective of this work is to invite the medical body to participate in a preventive campaign directed to detect dysplasia of the hip in the newborn and to obtain, with an early treatment, the solution to this severe nosological and social problem.


[The Saethre-Chotzen syndrome (acrocephalosyndactylia type III)].

A ten year old girl with Saethre-Chozen's syndrome and normal intelligence is described and her phenotype is compared to previously reported cases.


[Kernicterus in a premature infant with a minimun bilirubin amount].

A case of kernicterus in a premature neonate whose highest level of serum indirect bilirubin was 1 mg. is reported. The predisposing factors are discussed and a strong emphasis is placed upon the need for prevention.


[The general integral medical plan. Preliminary report].

A  pilot plan of medical studies was started in 1974 as a tentative solution to problems found in general medical practice and in medical education. This article is only a part of the integral evaluation and describes the attitudes assumed by the students when confronted with sets of objectives. Their responses are evaluated and will be used in the prosecution of determined aims.


[Elongation of the columella in patients with bilateral [abial fissure].

The results of secondary nasal tip elongation in bilateral cleft lip were analyzed. Brown and Mc Dowell's, Cronin and Millard's techniques, were used in thirty-five patients, who were seen at the Cleft Lip and Palate Clinic at the Hospital Infantil de Mexico for a five year period (1970-1975). Such correction was performed in 16 patients following Brown and Mc Dowell's technique, 10 by Millard, 8 by Cronin's and just one by Abbe Stlander's technique. 60% of the patients were males and 40% were females. The follow-up control (5 years) was made in 30 patients; the results are shown.


[Juvenile rheumatoid artritis (a single or various diseases?].

Some characteristics of juvenile rheumatoid arthritis that appeared in recent literature have led us to think that it can be divided into the following four groups: I. Seronegative poliarthritis, with more or less systemic symptoms. With the same characteristics it may appear in adulthood. II. Seropositive poliarthritis, identical to the adult rheumatoid arthritis. III. B-27 negative oligoarthritis, complicated frequently with chronic uveitis and autolimited course. IV. B-27 positive oligoarthritis evolving to ankylosing spondylitis. These groups may represent different diseases.


[Congestive heart failure].

A description is made of what it is and what causes a congestive heart failure, together with the symptoms. The aim of a treatment is to increase the strength and efficiency of the heart contraction and to reduce abnormal retention of sodium and water. To achieve this, several regimens and drugs are used.


[Heart arrest and reanimation].

The author describes when stoppage of the heart muscle is really true and the most important causes of it. It is an emergency that must be prevented and to achieve this, the premonitory symtoms and their treatment are described.


[Cystinolysinuric lithiasis].

Cystinuria is a disease characterized by the excessive  elimination of cystine and of dibasic amino acids (lysine, arginine, and ornithine) through urine of homozygotes. This study included 6 children complaining of abdominal pain with or without hematuria. The existence of renal radio-opaque lithiasis was confirmed in 5 of them and in the sixth, it was vesical. The clinical and analytic data were practically normal with the exception of the qualitative test of the amino acid urinary excretion that showed increase in urinary excretion of cystine. Likewise, percentages of tubular reabsorption were pathological in all the patients showing values between 35.4% and 74%. The diagnosis of systini-lysinuric lithiasis was established through amino acid excretion study in the six patients which was below normal; it fluctuated between 36% and 74%. Lysine, together with cystine, was the most frequently affected.


[Lymphocyte membrane markers in monoclonal gammopathies].

The distribution of peripheral blood lymphocytes with immunoglobulins (Ig) in 14 patients with monclonal gammapathies has been studied. The patients have been divided in two groups, one including patients never treated, the other those studied during or after treatment. The results, compared with 11 control subjects, show that lymphocytes with surface Ig from the same class of the serum paraprotein increased in every case of the first group and in some cases of the second.


[Physiopathological study in 2 cases of Bartter's syndrome].

Batter's syndrome is characterized by retardation in growth pitressin-resistant hypostenuria, hypokalemic alkalosis, high activity of the jux angiotensin-renine-aldosterone system with normal blood pressure; vascular insensibility to angiotensin and hypertrophy and hyperplasia of the juxtaglomerular apparatus. In both patients we studied, we found negative balance of sodium and potassium conditioned to a renal loss of them.


[Behavior and clinical significance of the eAg/ anti-e system in carriers of HBsAg].

An investigation has been carried out in 315 patients with acute and chronic HBsAg positive and negative hepatitis in order to study the relationship between a new recently identified antigen/antibody system designed eAg/anti-e and HBV pathology. eAg was detected in sera of 37,8% patients with acute hepatitis who recovered normally and of 65% patients with acute protracted hepatitis and circulating HBSAg. eAg was not found in the serum of any of 52 cases of acute HBsAg negative hepatitis. Prevalence of eAg positivity was also demonstrated especially in patients with more severe forms of chronic hepatitis. Anti-e was not found in any of 20 patients with acute protracted hepatitis, but in 40% of subjects with acute hepatitis who recovered, in 54,5% of asymptomatic HBsAg carriers and in 30% of patients with chronic persistent hepatitis. Our results confirm the specific association between eAg/anti-e system and hepatitis B infection and indicate that eAg determinant is associated with continuing activity and chronicity of hepatitic process. In contrast, anti-e is correlated with normal recovery of acute hepatitis, but it may be indicative also of asymptomatic carriage of HBsAg and of non-progressive liver disease.


[Usefulness of bone-marrow culture in the etiological diagnosis of septicemia].

Considerations are made on the importance of septicemia and the difficulty for an early diagnosis in most patients. The great usefulness shown by bone-marrow culture in the diagnosis of typhoid fever is pointed out and it is considered that this procedure may lend great help in the etiologic diagnosis of general infections. Twenty patients with septicemia are analyzed and the frequency of bone-marrow culture and of blood culture positiveness are compared and it is found that the percentage is greater for the first than for the second.


[Histotypes HL-A in the Ligurian population of the islet San Pietro in Sardinia].

The frequency of 17 HLA antigens of loci A and B has been studied by microlymphocytoxicity test in 114 subjects of islet S. Pietro, very close (a few miles) to South-west of Sardinia, but genetically very different from it, deriving the population from a region (Liguria) of continental Northern Italy. The data have been compared with those of a village of Southern Sardinia and with those of a population living in Liguria (continental Italy). The results confirm the striking genetical difference between people of the two islands (S. Pietro and Sardinia) and the close similarity between S. Pietro and Liguria from the genetical point of view.


[Composition of the cerebrospinal fluid in the premature newborn infant].

The composition of the spinal fluid was determined in 54 healthy premature infants in the first week of life. The infants were divided into three groups according to their gestational age; the results in each group, submitted to variance analysis, indicated similar values. The results in these premature infants were then compared with those in 79 normal full-term infants. The spinal fluid of the pre-term children showed higher bilirubin concentrations, more hemoglobin and higher levels of protein, indicating a greater permeability and immaturity of the blood-brain barrier. There were more erythrocytes in the premature infants, while the number of leukocytes and their differential count were similar in both groups; the only difference was the number of eosinophils, which were absent in the premature infants.


L-histidine ammonia-lyase from a T-strain Mycoplasma (Ureaplasma urealyticum).

L-histidine ammonia-lyase (E.C. 4.3.1.3) activity was shown to occur in cell-free extracts of Ureaplasma urealyticum. The activity of the crude enzyme depends on the presence of thiol compounds. However, higher than optimal concentrations of reduced glutathione, were shown to cause some inhibition of enzyme activity. This enzymatic reaction is characterized by a "lag" phase, whose duration depends on assay conditions. The substrate saturation curve shows a sigmoidal pattern probably due to the presence (in crude enzyme preparations) of some inhibiting impurity which reversibly combines with the substrate. Statistically significant increases of enzyme activity were demonstrated in crude enzyme preparations obtained from mycoplasma cells grown in broth medium supplemented with 16 mM L-histidine.


[Infectious agents in diarrhea of hospitalized children in Costa Rica].

Shigella, toxigenic Escherichia coli (stable toxin) and rotaviruses were frequently found among 50 children hospitalized with diarrhea studied during one year. These agents were less common among 45 controls without diarrhea, of comparable age and from the same wards as the cases reported. There was a greater frequency of respiratory symptoms in the diarrhea associated with rotaviruses. These were characterized by frequent bowel movements and vomiting and often fever. The bacterial diarrheas showed, in general, a more severe clinical picture than the viral ones. The rotaviruses had a low endemic level during April-October, but their prevalence increased in December and January; in such months these viruses were found in more than 50 per cent of the diarrheal cases.


[Microbiological pollution of the environment due to breeding. I. Enterobacteriaceae due to cattle breeding].

Enterobacteriaceae from faeces of cattle belonging to four cattle farms situated in the Ferrara district were investigated. At the same time, investigation was made of effluent sewage and recipient wells (upstream and downstream). The cattle (of the Italian Frisona breed) resulted uncontaminated by Salmonellae, but proved to be very susceptible to Arizona, Citrobacter, Shigella and S. gallinarum-pullorum infections, coming from the environment. Predominant species in faeces were as follows: Proteus, Klebsiella, Enterbacter and coliforms. One farm proved to be heavily polluted by Edwardsiella tarda. Yersinia enterocolitica strains were also isolated from faeces and sewage.


The influence of carbohydrate-containing media on some biological properties of Staphylococcus aureus.

After growth of S. aureus strains on glucose medium all the colonies obtained were negative for coagulase production. About half of the colonies grown on mannitol or maltose media were coagulase negative. Thermostable-nuclease and hemolysin activity were not affected by the carbohydrate media.


[Blood coagulation disorders in infants with infectious gastroenteritis].

The study included 28 infants with infectious gastroenteritis who evolved with disturbances of coagulation and in whom laboratory tests were practiced by micromethods through capillary puncture. The most frequently seen abnormality was a combination of vitamin K dependent factors deficiency with thrombocytopenia. Another observation in our study is that hypofibrinogenemia in infants with infectious gastroenteritis is not always secondary to disseminated intravascular coagulation. A decrease in fibrinogen in these cases is explained by a lack in synthesis of this factor in infants with malnutrition since out of 16 malnourished infants, 75% evolved with hypofibrinogenemia, while eutrophic infants evolved with normal fibrinogen. The disseminated intravascular coagulation syndrome was seen more frequently in patients with infectious gastroenteritis complicated with septicemia and shock, 57% of the patients did not show manifestations of bleeding nor of thrombosis which justifies in these cases a systematic investigation of the coagulation mechanism.


[Effects of diphtheria and tetanus toxins on liver regeneration in the rat].

The effects of diphtheria toxin and tetanus toxin on the regenerating rat liver were studied. The following parameters were used: liver regeneration percentage, mitotic index, protein content and serum complement C3 fraction level. Diphtheria toxin does not affect the liver regeneration, that what confirms the poor sensitivity of the rat to this toxin. Tetanus toxin inhibits the cellular division, while causes an increase in the cell protein content, resulting in hepatocyte hypertrophy. Both toxins cause a fall of the serum complement C3 fraction.


[Hemodynamic and respiratory function following acute spinal cord injury (author's transl)].

Twenty two cases of the cervical and thoracic cord injury were studied to determine hemodynamic and respiratory function within 7 days from the injury. Most patients showed a tendency of bradycardia and hypotension on admission which were more remarkable in the group of lower cervical cord or the upper thoracic cord lesion than the upper cervical cord group. Such a hypotension and bradycardia tended to recover within 7 days. In cervical cord injury, cardiac output remained unchanged, which indicated that initial hypotension was due to decreased total peripheral resistance. Respiratory rate was slightly increased in most patients, but did'nt show any significant difference among the level of the lesion. PaO2 and PaCO2 were within normal range on admission, however PaO2 decreased gradually in 7 days only in cervical cord injury. Increased pulmonary arterial pressure was confirmed during the above hypoxemic period. It suggests that disturbance of neurological control of pulmonary circulation might play a significant role in the respiratory insufficiency of cervical cord injury.


Thyrotoxicosis and lactate-producing angina pectoris with normal coronary arteries.

Three patients with thyrotoxicosis are described, in whom the presenting symptom was severe cardiac pain at rest or on effort and who were admitted to hospital with suspected or proven myocardial infarction. All patients were studied by selective coronary arteriography and left ventriculography after thyroid function tests which confirmed thyrotoxicosis. There was no demonstrable disease of the major coronary arteries in any of the patients, yet myocardial infarction and left ventricular aneurysm were shown to be present in 1, and there was definite electrocardiographic evidence of ischaemia in all 3. In addition, under stress the myocardium of all 3 patients produced lactate. It is recommended that thyrotoxicosis be seriously considered in the differential diagnosis of cardiac pain, particularly in younger women. The cause of the pain seems related to the cellular effects of thyrotoxicosis on the myocardium and current views of these effects are summarised. Of the 3 patients, 1 died suddenly 6 months after becoming euthyroid, indicating that the disease may not be as benign as expected. A guarded prognosis and continued medical follow-up are recommended when thyrotoxicosis presents with angina pectoris even when normal coronary arteries have been demonstrated.


Effect of verapamil studied by programmed electrical stimulation of the heart in patients with paroxysmal re-entrant supraventricular tachycardia.

Atrioventricular (AV) conduction, ventriculoatrial (VA) conduction, and the mechanism of tachycardia, were studied by programmed electrical stimulation before and after the administration of verapamil, in 10 patients with paroxysmal re-entrant supraventricular tachycardia. In 7 patients the tachycardia circuit was confined to the AV node. In 3 patients an accessory pathway conducting only in the ventriculoatrial direction was used during tachycardia. When administered intravenously during tachycardia, verapamil terminated the arrhythmia in 9 patients. Verapamil lengthened the effective and the functional refractory period of the AV node and the AV nodal transmission time in all patients in whom this could be studied. As a result of these changes, it was not possible to initiate tachycardia in 3 patients. The width of the zone of atrial premature beats able to initiate tachycardia (the tachycardia zone) narrowed in 5 patients, and increased in 2 patients. In 6 of these 7 patients the tachycardia zone shifted to longer premature beat intervals. Verapamil resulted in slowing of the heart rate during tachycardia. Apart from slowing in heart rate during tachycardia and termination of tachycardia after intravenous verapamil, the 3 patients with an accessory pathway showed no beneficial effect of verapamil on the mechanism of initiation of tachycardia. Five patients were restudied after 2 to 3 weeks of oral administration of verapamil. Though less, effects were similar to those obtained after intravenous administration.


Vasodilator therapy in acute myocardial infarction. Use of sublingual isosorbide dinitrate.

The haemodynamic effect of a long-acting vasodilator isosorbide dinitrate has been studied in 10 patients after an acute myocardial infarct, all of whom had evidence of left ventricular failure. Left ventricular filling pressure measured as the mean pulmonary artery wedge pressure was raised in all patients and fell significantly from 20+/-6 to 13+/-5 mmHg (P less than 0-001) within 10 minutes of sublingual isosorbide dinitrate. This 35 per cent fall in left ventricular preload was accompanied by significant fall in mean pulmonary artery pressure from 30+/-7 to 20+/-4 mmHg (P +less than 0-001) and mean right atrial pressure from 11+/-3 to 6+/-2 mmHg but cardiac output measured by thermodilution was unchanged. Mean systemic blood pressure was also significantly reduced. This improvement in left ventricular performance resulting from a reduction in left ventricular filling pressure and systemic blood pressure indicates that there may be a place for long-acting vasodilator in the treatment of acute myocardial infarction.


Two-dimensional echocardiography with a wide angle (60 degrees) sector scanner.

A wide angle (60 degrees) sector scanner producing a real-time two-dimensional echocardiogram has been used to examine healthy infants, children, and adults. Its method of use is described and findings from longitudinal and transverse scans are presented. The points of difference between the various types of electronic and mechanical two-dimensional scanning systems are discussed. This equipment minimises problems of chest contact and rib and lung interference and, by providing echocardiograms of high line density from a wide angle, is a suitable real-time two-dimensional scanning system for examining patients of all ages.


Aortic root and left atrial wall motion. An echocardiographic study.

The echocardiographically recorded movement of the aortic root was studied by analysing the relation between posterior aortic wall motion and other intracardiac events. The systolic anterior movement of the aortic root continued beyond aortic valve closure and in cases with mitral regurgitation began significantly earlier than in normal subjects. The diastolic rapid posterior movement began after mitral valve opening but did not occur in patients with mitral stenosis. The total amplitude of aortic root motion was increased in patients with mitral regurgitation, diminished in cases of mitral stenosis, and was normal with aortic regurgitation. In patients with atrioventricular block an abrupt posterior movement followed the P wave of the electrocardiogram irrespective of its timing in diastole. These observations correlate with the expected changes in left atrial volume during the cardiac cycle both in the normal subjects and patients with heart disease. The results support the hypothesis that phasic changes in left atrial dimension are largely responsible for the echocardiographically observed movement of the aortic root and indicate a potential role for echocardiography in the analysis of left atrial events.


Assessment of ventricular elements of mitral valve by left ventriculography.

In the left ventriculogram in the right anterior oblique projection the plane of the mitral valve is seen in profile and the papillary muscle shadows are outlined. The distance from the middle of the papillary muscles to the plane of the mitral valve during systole was used to assess the average length of the chordae tendineae, and the area of the papillary muscle shadows was measured as an index of hypertrophy in a series of hearts with mitral valve disease. Valvar mitral stenosis is characterised by slight reduction in the length of chordae tendineae and more hypertrophy of the papillary muscles, while in subvalvar mitral stenosis there is more shortening of the chordae tendineae and less papillary muscle hypertrophy. Valvotomy may lengthen the chordae tendineae in subvalvar mitral stenosis. In rheumatic mitral regurgitation length of chordae tendineae and papillary muscle size were normal. The measurements were not useful in assessing non-rheumatic mitral regurgitation.


Functional status of patients with large ventricular septal defect and pulmonary vascular disease 6 to 16 years after surgical closure of their defect in childhood.

We have reviewed 27 patients now 6 to 16 years after closure of a ventricular septal defect at 3 to 12 years of age associated with pulmonary hypertension with a view to assessing their quality of life, respiratory function, and exercise performance. All the patients led normal unrestricted lives. Their subjective lack of symptoms was, in general, confirmed by the results obtained from assessment of lung function tests and two-stage exercise testing in 19 volunteers. Abnormal ventilation in relation to work load was noted in 5 patients and a slightly low exercise cardiac output in 6. Although the patients led normal lives and had a satisfactory response to exercise, measurement of pulmonary artery pressure showed striking pulmonary hypertension on effort. Despite the satisfactory progress of these patients their more long-term future must be one of conjecture and their residual pulmonary hypertension, indicative of residual pulmonary obstruction, must lend weight to arguments for earlier closure of ventricular septal defect before 1 to 2 years of age when changes in the pulmonary vascular bed may be reversed after closure of the defect.


Modified axial lead system in children.

Preliminary studies have been made on the use of the modified axial lead system in infancy and childhood. A highly significant correlation between internipple distance and height suggested that internipple distance be used as an index for the selection of a template to facilitate placement of the chest electrodes (Z and X). A series of 4 triangular templates was designed. The use of a template one size too large or too small was shown not to lead to any significant error in waveform measurement. A further study showed that the reference level for the application of the praecordial electrodes should be the 5th intercostal space as for adults, but that no serious diagnostic error was likely to arise if the 4th or 6th intercostal space was chosen by mistake. A study of the Frank lead system suggested that the use of the 5th intercostal space as a reference level was more appropriate than the 4th intercostal space, which is generally adopted by users of that system. The conclusion reached was that the axial lead system is the preferred orthogonal lead system for children, with templates for 4 ranges of internipple distance (less than 10 cm; 15 to 20 cm; and less than 20 cm--adult build) being proposed to simplify electrode placement.


Training and electrocardiographic abnormalities in the elderly.

Electrocardiograms (CM5 lead, where one lead is attached in the V5 position and one at the manubrium sterni, with the neutral lead on the back of the neck) have been recorded from 14 men and 25 women aged 60 to 75 years, at rest, during progressive bicycle ergometer exercise to 75 to 85 per cent maximum oxygen intake, and during the subsequent recovery phase. Earlier studies showing a high frequency of ischaemic electrocardiographic abnormalities in women are confirmed; it is suggested that this may reflect a high work load per unit mass of myocardium. Training induces an elevation of the ST segment at rest and during recovery, with a reduction in ST depression during work at a given heart rate, the exercise changes being related to the intensity and frequency of training selected by the subject. Possible explanations of the response to regular exercise include not only the development of the collateral circulation, but also a lessening of the hyperkalaemia of effort and a reduction in the work load per unit mass of myocardium secondary to hypertrophy or a change in the average dimensions of the heart.


Ischaemic heart disease in the elderly.

Studies were made for evidence of heart disease on 501 people aged 65 and more living at home; 22-4 per cent had clinical and/or electrocardiographic evidence of ischaemic heart disease. The prevalence of ischaemic heart disease increased with age, and was slightly greater in men than women. The frequency of ischaemic heart disease increased with increasing current cigarette consumption and with total cigarette consumption. There was no increase in relation to any of the following possible risk factors: systolic and diastolic blood pressure, blood glucose, serum cholesterol, skinfold thickness, percentage of ideal body weight. The survival over a 5-year period of all subjects with ischaemic heart disease did not differ significantly from that of all subjects together, but the mortality of subjects with ischaemic heart disease and an abnormal electrocardiogram was 1-5 to 2 times that of subjects in whom ischaemic heart disease was diagnosed on the basis of angina pectoris or past cardiac infarction, the electrocardiogram being normal.


Long-term prognosis of treated acute massive pulmonary embolism.

Seventy-two patients surviving initial treatment by pulmonary embolectomy, streptokinase, or heparin for acute massive pulmonary embolism have been reviewed 1 to 9 years later. Of these patients, 17 had additional cardiorespiratory disease. There were 12 late deaths (41% of those patients with, and 9% of those patients without additional cardiorespiratory disease). No death was due to chronic pulmonary hypertension, and none to certain recurrence of pulmonary embolism. The causes of death were malignant disease (6 patients), cardiopulmonary disease other than pulmonary embolism (4 patients), and 'sudden' (2 patients). Though venous interruption surgery was not used, and long-term anticoagulation rare, the incidence of possible or probable recurrent embolism was low (6%). There was no definite evidence of persistence or subsequent development of pulmonary hypertension after treatment in any patient. Resolution of embolism as judged by symptoms, signs, electrocardiogram, and chest x-ray examination was almost always complete. Some pulmonary arteriograms 1 to 6 months after initial treatment showed minor abnormalities, but others at a later date were normal. Perfusion lung scans carried out 1 to 8 years after initial treatment often showed minor abnormalities.


Nomogram for calculation of left ventricular volumes.

A nomogram has been devised for the rapid derivation of left ventricular volumes from single-plane angiograms obtained in the 30 degrees right anterior oblique projection. The left ventricular volumes are derived from the use of the area-length formula of Dodge. The computed left ventricular volumes may then be adjusted to correspond to the actual volumes by an appropriate conversion chart.


Fistula from coronary arteries to left ventricle after myocardial infarction.

Coronary arteriography and left ventriculography, performed in a 42-year old patient with unstable angina seven months after a myocardial infarct showed communications from both the left anterior descending and right coronary arteries to the left ventricular chamber. The area of communication corresponded to the site of infarction as established by electrocardiogram and left ventriculogram. Whether this is a congenital or acquired lesion is unclear.


Varicella myocarditis presenting with unusual ventricular arrhythmias.

A 10-year-old boy with varicella developed syncopal episodes caused by runs of self-terminating ventricular tachycardia and ventricular fibrillation. These arrhythmias were thought to be caused by varicella myocarditis and were resistant to most common antiarrhythmic agents. Continuous electrocardiographic recording and analysis proved extremely useful in the management of this case. Mexiletine, a new antiarrhythmic drug, was finally effective in controlling recurrent attacks of ventricular tachycardia.


Recurrent migraine after propranolol.

A 70-year-old woman with angina pectoris developed a migrainous headache 3 days after starting oral propranolol. She had not complained of headaches since her second and third decade when she had suffered occasional attacks of migraine. It is likely that propranolol was the cause of her headache, since it recurred when she was rechallenged with the drug.


Lack of mutagenic effect of halothane or chloroform on cultured cells using the azaguanine test system.

Halothane with and without nitrous oxide and chloroform alone were tested for mutagenic effects at the 8-azaguanine locus on the chromosomes of Chinese hamster lung fibroblast cells in culture. No significant numbers of mutations were found after 24 h exposures to 1-3% of these anaesthetics, or to 75% nitrous oxide.


Effect of intermittent exposure to a low concentration of nitrous oxide on haemopoiesis in rats.

Wistar strain albino rats were exposed to 1% nitrous oxide in air for periods ranging from 1 week to 6 months. Their peripheral blood and bone marrow were examined for evidence of alterations in haemopoiesis. Apart from a transient polycythaemia during the first week no change in haemopoiesis was found.


Evidence of a role for the peripheral chemoreceptors in the ventilatory response to doxapram in man.

In seven normal subjects premedicated with atropine and pethidine and lightly anesthetized with thiopentone, the ventilatory response evoked by doxapram 20 mg i.v. was delayed on average from 15.7 s to 23.0 s when changing from air to oxygen breathing. Mean VE, immediately after the administration of doxapram was increased by 3.3 litre and 1.9 litre when breathing air and oxygen respectively. These findings indicate that doxapram has an effect on the peripheral chemoreceptors and are consistent with drug activity on both peripheral and central respiratory control mechanisms.


Observed and predicted accumulation of local anaesthetic agents during continuous extradural analgesia.

After lumbar extradural injections of ligocaine or etidocaine for surgical anaesthesia further accumulation in the plasma was minimal following top-up injections for pain relief after operation. The dose regimens were: 20 ml of 2% plain lignocaine HCl solution for surgical anaesthesia followed by 10 ml every 1 h until 4 h, and 20 ml of 1% plain etidocaine HCl solution for surgical anaesthesia followed by 10 ml every 2 h until 8 h. Plasma drug concentrations measured after initial doses were used to predict those following successive doses. Agreement between predicted and experimental values was good and further projections were made concerning the local accumulation of etidocaine.


The binding of thiopentone to kwashiorkor serum.

The binding of thiopentone to normal and kwashiorkor serum has been investigated. It has been confirmed that thiopentone is bound to albumin predominantly. In kwashiorkor serum, less binding to albumin occurs, but secondary binding sites appear. The significance of these observations is discussed.


The interrelation of personality and postoperative factors.

A composite statistical analysis was made of the results from four trials comprising patients undergoing upper abdominal operations. It revealed a marked correlation between the neuroticism score as measured by a personality inventory before operation and the percentage vital capacity impairment found after operation. Neuroticism correlated also with pain as measured by a visual analogue scale. The vital capacity impairment and subjective pain readings were interrelated and both neuroticism and vital capacity impairment were related to the chest complication rate. Personality assessment before operation can identify one group of patients who will have marked pain and limitation of vital capacity after operation.


Serum cholinesterase: effect on the action of suxamethonium following administration to a patient with cholinesterase deficiency.

Purified serum cholinesterase 90 mg was administered to a patient with cholinesterase deficiency. The effect on the action of suxamethonium was studied. The half-life (44.7 h), time constant (64.5 h), rate constant (0.0155 h-1) and distribution volume (2740 ml) of the cholinesterase activity were determined.


Macroautoradiographic study of the distribution and excretion of 14C-pentobarbitone in rats pretreated with phenobarbitone.

The distribution and excretion of pentobarbitone were studied, using macroautoradiography, in two groups of rats at times ranging from 1 min to 70 min after the i.v. injection of 100 muCi given as 30 mg/kg of 14C-pentobarbitone. In a control group, the carbon-14 concentration (concentration of pentobarbitone) in the brain remained always greater than that in heart blood (unchanged pentobarbitone and metabolites). In a group subjected to enzyme induction (pretreated with phenobarbitone), however, the carbon-14 concentration in the brain exceeded that in the heart blood initially and then decreased rapidly. In the induced group, the carbon-14 concentration in the urine and small intestine (almost all of which was metabolites) increased with time. In particular, 70 min after the injection, the carbon-14 concentration in the small intestine of the induction group was twice that of the control group. It was concluded that in the induction group the rapid decrease in carbon-14 concentration in the brain was mainly a result of an increase in the metabolic breakdown of pentobarbitone in the liver.


Effect of thiopentone on myocardial function.

In a canine preparation designed to separate myocardial from peripheral cardiovascular effects of the drug. It was found that thiopentone produced minimal depression of the heart. Only in much greater concentrations was significant depression found. It is concluded that the cardiovascular effects of thiopentone i.v. are not a direct effect on the heart.


Estimation of blood enflurane concentrations by gas-liquid chromatography.

A simple and reliable method for the estimation of enflurane concentrations in whole blood is described. This involves exraction with n-heptane and estimation by gas-liquid chromatography using methoxyflurane as an internal standard. Reproducibility was good and extraction from whole blood was reliable.


Clinical impressions of enflurane.

Enflurane was used in 150 non-selected patients and was found to be a most satisfactory inhalation anaesthetic. Induction and recovery times were rapid and these characteristics, together with its rather pleasant smell, made it readily acceptable to the patient. Although such features suggest that it would be an ideal agent for children, very high concentrations of enflurane were required to produce adequate anaesthesia in infants and small children. Normal sinus rhythm continued following the injection of adrenaline during enflurane anaesthesia and adequate muscle relaxation was obtained for lower abdominal surgery. The degree of metabolic breakdown of enflurane is considerably less than with other inhalation agents and, if this is reflected in terms of minimal renal and hepatic toxicity, there is every reason to believe that enflurane may be preferable to the volatile anaesthetics currently in use.


Enflurane (Ethrane) anaesthesia in man. Metabolism and effects on biochemical and haematological variables.

In 10 patients serum inorganic fluoride increased to a mean peak value of 16 micronmol.litre--1 after 2 h of enflurane anaesthesia. Four days after anaesthesia, serum inorganic fluoride had decreased to the values before operation. The maximum daily inorganic fluoride excretion in urine (UFV) did not exceed 200 micronmol.litre--1. In a group of 20 patients routine biochemical and haematological variables were measured before and after enflurane anaesthesia. There were only minor changes in these variables, attributable to the surgical procedure. It is concluded that renal dysfunction is unlikely to follow enflurane anaesthesia in patients with previously normal hepatic and renal function.


Hepatitis-B virus infection in anaesthetists.

To determine whether anaesthetists are at risk from developing hepatitis-B virus (HBV) infection from their patients, 95 anaesthetists working with black South Africans (who have a high prevalence of hepatitis-B antigenaemia) were questioned about attacks of viral hepatitis and their blood was tested for hepatitis-B (surface) antigen (HBsAg) and antibody (Anti-HBs). Anti-HBs was detected in the serum of 17.9% of the anaesthetists, but none was a chronic carrier of HBsAg. Two anaesthetists had suffered from acute viral hepatitis during their careers, one of whom is now positive for Anti-HBs. Forty-five of the anaesthetists (47.4%) were known to have anaesthetized patients with HBs antigenaemia, and of these seven were Anti-HBs-positive. Anaesthetists working with a population having a high carrier rate of HBV appear to be more at risk from HBV infection than the general population.


Haemodynamic responses to antagonism of bocurarine block with atropine-neostigmine mixture in children.

Following antagonism of tubocurarine block with a mixture of atropine 20 microgram/kg and neostigmine 50 microgram/kg in 20 children, heart rate decreased from a control value of 110.4 beat/min to 90.1 at 5 min and 89.2 at 6 min (P less than 0.02). Stroke volume index did not change during the first 5 min from a control value of 36.3 ml. beat--1.m--2 but a significant increase to 48 ml. beat--1. m--2 was observed at the 6th and 7th mins following the injection of the mixture (P less than 0.05). Cardiac index and mean arterial pressure remained unaltered throughout the period of observation. Normal sinus rhythm was maintained in all patients. It was concluded that antagonism of tubocurarine with an atropine-neostigmine mixture does not produce any important haemodynamic change in children.


Modification of the circulatory effects of extradural block combined with general anaesthesia by the addition of adrenaline to lignocaine solutions.

The cardiovascular changes associated with extradural block were measured in two groups of patients who were also receiving light general anaesthesia. In the first two group (five patients) 2% plain lignocaine 20 ml was used and decreases occurred in mean arterial pressure, cardiac output, stroke volume and peripheral resistance. In the second group (10 patients) 2% lignocaine 20 ml to which adrenaline 1:200,000 had been added was used. Decreases in arterial pressure and peripheral resistance occurred in all patients, but the responses of the cardiac output and heart rate were variable, decreasing in three patients and remaining stable or increasing in seven patients. A high segmental block was presumed to have occurred in those patients who developed bradycardia and a decreased cardiac output. The differences between these studies in anaesthetized patients and those previously reported in conscious volunteers are discussed.


Some circulatory and respiratory effects of morphine in patients without pre-existing cardiac disease.

Haemodynamic and respiratory effects of i.v. morphine (10 mg/70kg body weight) were studied in 10 adults with unimpaired circulatory function. There were significant changes in mean arterial pressure, mean heart rate, respiratory rate and tidal volume, at 10-, 30- and 60-min intervals. Transient changes in mean total systemic resistance and mean stroke volume were also seen at 10 min. The results strongly suggest a peripheral vasodilator response to morphine. Respiratory depression was not demonstrated.


Peripheral vascular effects of morphine in patients without pre-existing cardiac disease.

The effect of doses of morphine (10 mg/70 kg) on the forearm blood flow and vascular resistance was evaluated in 10 adults. The present findings were correlated with the central haemodynamic changes observed previously. Consistent and significant increases in forearm blood flow and significant decreases in forearm vascular resistance were observed in all patients.


Anaesthesia for patients susceptible to malignant hyperpyrexia. A study of pancuronium and methylprednisolone.

In a study of human malignant hyperpyrexia-susceptible muscle a comparison between pancuronium and methylprednisolone showed that both drugs produced qualitatively similar depression of the halothane-induced muscle contracture. From this and other evidence, it is suggested that pancuronium is a suitable drug for use in malignant hyperpyrexia-susceptible patients.


Preoperative serum cholinesterase concentration in chronic renal failure. Clinical experience of suxamethonium in 81 patients undergoing renal transplant.

Serum cholinesterase concentrations were measured in 181 patients in chronic renal failure. Significant differences in cholinesterase concentrations were not found in patients undergoing dialysis and changes appear to be independent of the method of treatment used. Clinical experience with suxamethonium to facilitate tracheal intubation was satisfactory in 80 patients undergoing renal transplant. Apnoea occurred in one patient who was found subsequently to have atypical cholinesterase inheritance.


Adverse reactions to procainamide.

1 Data from a comprehensive drug surveillance programme are analysed to provide details of procainamide use and toxicity in medical wards of teaching hospitals in five countries. 2 Out of a total of 488 recipients 9.2% had one or more adverse effect attributed to the drug; common effects being arrhythmias, gastro-intestinal upsets and drug fever. Although occasionally of major severity, no patient died as a consequence of procainamide toxicity. 3 Toxicity was directly related to total daily dose and duration of hospitalization but was not related to age, weight of the patient or presenting urea or albumin concentrations.


Cardiovascular effects of a new inotropic agent, U. K. 14275, in patients with coronary heart disease.

1 The chronotropic and inotropic properties of U.K. 14275, a phosphodiesterase inhibitor were assessed in patients with coronary heart disease. 2 Left ventricular function was assessed in eight patients with acute myocardial infarction using the non-invasive measurement of systolic time intervals. 3 Twelve patients with angina pectoris were studied during diagnostic coronary arteriography. Left ventricular function was assessed using a high fidelity catheter tipped transducer in the left ventricle. 4 In both groups of patients U.K. 14275 infused intravenously in doses of 32, 64, 128 and 256 microgram kg-1 bodyweight min-1 enhanced the contractile state of the left ventricle without altering the heart rate.


Acebutolol metabolite plasma concentration during chronic oral therapy.

1 We have measured the plasma concentration of acebutolol and a major metabolite in patients on chronic oral therapy with this drug, using a new assay, specific for each species. Our study suggests: 2 The acetyl metabolite was present in concentrations greater than those of acebutolol at all times during the dosing interval in all seven subjects. 3 The ratio of the mean steady-state plasma concentrations of the acetyl metabolite to unchanged acebutolol was 2.7 +/- 1.0. 4 Previous studies using non-specific methods that measure plasma concentrations of the acetyl metabolite and acebutolol as a single species cannot be used to determine pharmacokinetic parameters or to provide reliable correlations of plasma drug concentration with effect. 5 Future studies determining plasma concentration of acebutolol should take this metabolite into account. 6 Further work will be necessary to determine the metabolite's contribution to acebutolol's effects in man.


Carbamazepine and carbamazepine-10, 11-epoxide concentrations in human brain.

1 Carbamazepine (CBZ) brain and plasma concentrations were measured in twenty-one patients undergoing brain surgery for tumour removal. The drug was administered prophylactically at doses ranging from 6.9 to 14.8 mg/kg for 4-5 days before the intervention. 2 In seventeen cases where sample were collected 10-14 h after dosing, CBZ brain levels ranged from 2.2-14.5 microgram/g. A significant linear relationship (p less than 0.01) was observed between brain and plasma concentrations with a brain/plasma ratio of 1.1 +/- 0.1. 3 Carbamazepine 10,11-epoxide (CBZ-Epox), present in all samples, could be quantified in three brain specimens. Its brain concentrations ranged from 1.5-2.7 microgram/g with a brain/plasma ratio of 1.1-1.2. 4 Parieto-occipital areas tended to show higher CBZ concentrations while lower values were found in temporal regions. Very low CBZ levels were found in two gliomas while in meningiomas CBZ levels were similar to those observed in normal tissue. 5 The data, showing a linear relationship between brain and plasma concentrations of both CBZ and its epoxide, give additional significance to the plasma level monitoring of antiepileptic drugs.


Factors influencing plasma phenobarbitone levels in epileptic patients.

1 Various statistical techniques were used to study the effects of age, sex and concurrent therapy with other anticonvulsants on the relation between plasma phenobarbitone levels and doses of (i) phenobarbtione, (ii) methylphenobarbitone or (iii) primidone, in epileptic patients. 2 Methylphenobarbitone and primidone are converted to phenobarbitone in the body. The mean doses of phenobarbitone, methylphenobarbitone and primidone which produced the  same plasma phenobarbitone level (15 microgram/ml) were, respectively, 1.75,2.75 and 7.75 mg kg-1 day-1. 3 For both phenobarbitone and methylphenobarbitone dose requirement to achieve a given plasma phenobarbitone level fell progressively with age. Sex influenced the relation between plasma phenobarbitone level and phenobarbitone or methylphenobarbitone dose. Interactions were detected between primidone and both phenytoin and carbamazepine. 4 In individual patients, within the limits of dosage studied, the relation between plasma phenobarbitone level and drug dose was not rectilinear if phenobarbitone itself was taken, but was rectilinear if methylphenobarbitone was taken.


The influence of age on the response to anticoagulants.

1 A group of 114 patients on long-term anticoagulant therapy was studied. The daily maintenance dose of both phenprocoumon, bishydroxycoumarin and warfarin was found to be significantly lower in patients aged between 61 and 70 years than in the those between 50 and 60 years of age. The mean daily dose of bishydroxycoumarin, hower, when expressed on a weight basis, was not significantly lower in the elderly. 2 For bishydroxycoumarin but not for phenprocoumon and warfarin there was found a statistically significant correlation between the daily maintenance dose and the weight of the patient. 3 The mean daily dose of both bishydroxycoumarin and warfarin was 30-40% lower than that recommended in the literature. 4 'Correction' was made for potential drug interference by excluding patients in continuous medication with order drugs known to influence the treatment with orally administered anticoagulants. The interindividual variation in dosage requirements of coumarin drug was thereby reduced in the age groups above 60 years. 5 The level of vitamin-k dependent coagulation factors, measured by Owren's 'P and P' method (PP%) was significantly lower (P less than 0.001) in patients of advanced age (between 61 and 70 years) than in younger patients (between 50 and 60 years). 6 The plasma concentration of albumin was significantly lower in patients over 60 years than in those under that age. 7 Correlation (P less than 0.01) was found between the daily maintenance dose of phenprocoumon and the plasma concentraction of albumin.


Plasma prednisolone levels from enteric and non-enteric coated tablets estimated by an original technique.

1 A quantitative thin layer chromatographic technique for the estimation of plasma prednisolone levels has been devised with a minimum level of estimation of 10 ng/ml. 2 A comparative study of the absorption of 5 and 10 mg prednisolone from enteric and non-enteric coated tablets (5 mg) was carried out in healthy subjects. 3 Mean plasma half-life and peak plasma concentrations obtained from the non-enteric coated preparation agree well with previous studies in normal subjects reported by other investigators using competitive protein binding or radioimmunoassay techniques. Intersubject variability in bioavailability was noted. 4 Enteric coating increased the lag time before prednisolone appeared in the blood but did not alter the bioavailability of prednisolone compared to the equivalent dose of the non-enteric coated tablet.


Prevention of adverse drug interactions.

1 The awareness and recognition of adverse interactions between drugs by prescribers is low. 2 A 6-month prospective study on patients on long-term outpatient anticoagulant therapy in the Grampian area has been carried out to evaluate a simple and cheap warning system. 3 The practitioners of patients in the test group were issued with warning labels which showed drugs known to interact. A reduction in the initiation of prescriptions for potentially interacting drugs was shown between the test and control groups (no warning labels). 4 The 140 practitioners who completed the study found the system to be convenient and useful. Extension to other high-risk drugs with the potential to interact with other drugs is planned. This system has the advantage of being drug and patient-orientated whereas lists of drug interactions or drug discs require more conscious effort by the prescriber.


The disposition of sodium fusidate in man.

1 In a pharmacokinetic study in six volunteers serum fusidic acid concentrations were obtained after rapid intravenous administration of 100 mg. 2 Analysis of the data suggests that the serum concentration/time curve is biphasic and that the curve can be described by the following equation: cp=5.9e(-1.82t)+4.3e(-0.13t). 3 The disposition characteristics of sodium fusidate have been calculated from this relationship and a plasma half life for sodium fusidate of between 5 and 6 h obtained. 4 Subsequently plasma fusidic acid levels have been measured in the same volunteers on three occasions after sodium fusidate (500 mg) given either as a slow intravenous infusion, or orally as a capsule or as a suspension. 5 Serum levels and AUC after a capsule were about 75% of those obtained after the infusion (30 and 70 mg/1 at peak respectively) whereas levels and AUC after the suspension were only about 50%.


Effect of nomifensine on brain amines and epilepsy in photosensitive baboons.

1. The literature, both clinical and experimental, suggests that tricyclic antidepressants are potentially epileptogenic. Using the experimental model of epilepsy provided by the photosensitive baboon, Papio papio, the epileptic potential of four antidepressant drugs, two of which are tricyclic, has been assessed. The drugs used were imipramine 1, 10 and 20 mg/kg, chlorimipramine 1, 10 and 20 mg/kg, maprotiline 1 and 10 mg/kg and nomifensine 10 and 20 mg/kg. In a second series of experiments the 5-hydroxytryptamine (5-HT) precursor 5-hydroxytryptophan (5-HTP) 10 and 25 mg/kg has been administered before administration of imipramine 10 mg/kg and chlorimipramine 10 mg/kg. 2. The results of the experiments indicate that at 10 mg/kg imipramine, chlorimipramine and maprotiline all induce seizures and lower the seizure threshold. In contrast nomifensine at this dose did not alter the seizure threshold. 5-HTP 25 mg/kg administered before the antidepressants, abolished seizures. These results are discussed in the light of other experiments which have attempted to explain the pathophysiology of epileptic seizures following antidepressants, and it is concluded that dopaminergic mechanisms are probably responsible for the differing effect noted with nomifensine.


A simple gas chromatographic method for the determination of nomifensine in plasma and a comparison of the method with other available techniques.

1. A rapid simple gas chromatographic technique for determining nomifensine in plasma is described. 2. Nomifensine is rapidly absorbed after oral administration to man. 3. Following a 100-mg dose, peak levels of an acid-labile conjugate of 2--3 microgram/ml are reached about 1.5 h after administration. 4. The conjugate is cleared with a half-life of between 1 and 2 hours.


Determination of nomifensine by a sensitive radioimmunoassay.

1. A radioimmunoassay (RIA) has been developed for determination of both nomifensine and total nomifensine (nomifensine + conjugated nomifensine) in serum, plasma, and urine. 2. Antibodies were prepared in rabbits by immunization with N-(8-Nomifensine) succinamic acid-bovine serum albumin. 3H-labelled drug was used as tracer. Separation of free from antibody-bound nomifensine was carried out using dextran-coated charcoal. For determination of total nomifensine, the acid-labile conjugate was split by acidification. 3. The limit of detection for nomifensine is 300 pg/ml plasma and the cross-reactivity of the metabolites is less that 1%. The influence of conjugated nomifensine on the results of nomifensine can be corrected. 4. Pharmacokinetics of nomifensine were determined in healthy volunteers after oral administration of 100 mg 14C-labelled drug. Peak levels of 14C radioactivity (2,150 ng/ml), total nomifensine (1,252 ng/ml) and nomifensine (53 ng/ml) appeared within 1.5-2 h; the half-life of elimination from plasma was 1.5-2 hours. The advantages of this routine method are high sensitivity, the requirement of small amounts of plasma, and simple handling.


Influence of nomifensine and desipramine on tyramine pressor responses in healthy volunteers.

1. Pressor responses following a series of bolus intravenous injections of tyramine were used to assess the influence of single oral doses of nomifensine 75 mg on peripheral sympathetic neuronal uptake mechanisms in healthy volunteers. Desipramine 50 mg served as a positive control. 2. Following each treatment the effect of tyramine was diminished, with a shift to the right in the tyramine dose-response curve. In addition, there was a suggestion that in these experimental conditions nomifensine was less potent than desipramine.


Effects of nomifensine in vitro on uptake of 5-hydroxytryptamine and dopamine into human platelets.

1. The effect of nomifensine on the uptake of 5-hydroxytryptamine (5-HT) and dopamine (DA) into human platelet-rich plasma has been studied. 2. A significant inhibition of DA uptake was observed at nomifensine 10(-6) M. 3. 5-HT uptake was significantly inhibited only at nomifensine 10(-4) M or more. 4. These results are consistent with those from previous animal experiments and suggest that the human platelet may be used as a model for studying DA uptake as well as that of 5-HT.


Effects of nomifensine, an inhibitor of endogenous catecholamine re-uptake, in acromegaly, in hyperprolactinaemia, and against stimulated prolactin release in man.

1. Nomifensine, an inhibitor of endogenous catecholamine re-uptake, did not affect the growth hormone (GH) or prolactin levels in patients with acromegaly or hyperprolactinaemia. It does not, therefore, have any therapeutic role in these conditions at the dosage used in this study. 2. It had no effect on thyrotrophin-releasing hormone (TRH)-induced thyrotrophin (TSH) or prolactin release in males, yet caused marked suppression of monoiodotyrosine (MIT)-induced prolactin release in males but not in females. 3. The significant suppression of MIT-induced prolactin release in males is likely to reflect the dopamine (DA) agonist activity of the drug and its lack of effect in the other situations tested could be dose related. 4. It is proposed that the difference in male and female patterns of prolactin response to MIT after nomifensine, could be due to a "damping" effect of oestrogen on the hypothalamic dopaminergic system.


A profile of nomifensine.

1. Nomifensine is a new antidepressant of novel chemical structure (a tetrahydroisoquinoline) with a pharmacological and therapeutic profile which differentiates it from any existing group of psychotropic agents. 2. The basic animal pharmacological profile is similar to that of the tricyclic antidepressants, imipramine and desmethylimipramine, but with a comparative lack of peripheral anticholinergic and cardiotoxic effects. 3. The pattern of effects on monoamine neurotransmitters is unique amongst antidepressants in that nomifensine is a potent dopamine agonist, has a powerful inhibitory effect on noradrenaline uptake and a weaker inhibitory effect on serotonin uptake. These pharmacological differences are reflected in the behavioural activity of the drug. 4. Clinically nomifensine has been shown to be an effective non-sedative antidepressant; its relative lack of anticholinergic and other somatic side-effects (particularly on the cardiovascular system) have been confirmed in patients.


A comparative review of the pharmacology of nomifensine.

1. Nomifensine is a new substance which showed, in tests for antidepressant activity, a pronounced effect which is quantitatively better than that of the reference substances. 2. With regard to thymoleptic effects in animal studies the effect of nomifensine is similar to that of tricyclic antidepressants, but nomifensine has no pronounced anticholinergic activity. 3. Nomifensine influences the cardiovascular system very slightly. 4. The mechanism of action of nomifensine differs from that of tricyclic antidepressants and must be clearly differentiated from phenylalkyl amines with sympathomimetric activity. 5. Nomifensine is a compound with a special, new profile of action, and thus cannot be calssified in known categories.


Enhanced growth of syngeneic Moloney sarcoma with decreased immunity in the regressors.

S.c. cellular transplants of MS tumours have a high incidence of rejection in adult BALB/c mice, which can then be used as syngeneic regressors. When these tumours were inoculated within a glass cylinder which had been implanted s.c. in BALB/c mice 2 days earlier, 51% of the animals died with progressively growing tumours, compared with 2% in animals which had received the same inoculum directly s.c. This experimental model demonstrates tumour enhancement in a syngeneic system, and duplicates what has been previously reported in two different allogeneic tumour-host combinations, where it was demonstrated that immunological enhancement was operating, since the addition of either progressor serum or soluble tumour antigen significantly increased tumour incidence. For the purpose of investigating whether the glass cylinder model could also modify the immune response of the host to a second tumour challenge, a leukaemia virus known to crossreact with MS was used. Regressors were challenged i.p. with a lethal dose of a leukaemia virus, PLLV. Regressors bearing a glass cylinder showed a 22% survival rate which was significantly lower than that of the s.c. inoculated regressors (71%). This decrease in cross-immunity suggests that the artificially constructed privileged site created by the glass cylinder, by conditioning for tumour enhancement, also decreases immunological memory.


Further investigations of the effects of the hypoxic-cell radiosensitizer, Ro-07-0582, on local control of a mouse tumour.

The tumour used, designated MT1, is a more radiosensitive form of the anaplastic MT tumour previously described. No explanation for the increased radiosensitivity was found, but it was shown not to be due to infection or to a change in immunological status, growth rate or histology. The sensitivity has remained constant throughout the present work. No cytotoxicity in the tumour was observed when 1 mg/g body weight of Ro-07-0582 was injected immediately after a single dose of X-rays; indeed a small protective effect was seen. A radiosensitization enhancement of 1-5 was achieved with a relatively low drug dose of Ro-07-0582 in a 5F/4d fractionated regime. The interval between the injection of a low dose of Ro-07-0582 and the start of irradiation was found to be critical, the optimum interval being 45-60 min. The subsequent incidence of distant metastases was not increased by the use of Ro-07-0582 at the time of "primary" tumour irradiation.


Effects of cytotoxic agents on TdR incorporation and growth delay in human colonic tumour xenografts.

The relationship between the utilization of 3H-thymidine in situ ([3H]-TdR fractional incorporation or TFI) and tumour growth delay after treatment with various cytotoxic agents has been examined. It is shown that (a) it is not possible to predict tumour growth delay, or to select the most effective agent, from changes in TFI 1 day after treatment; (b) there is a good correlation between tumour growth delay and the time for recovery of TFI to the pretreatment level; (c) there is a relationship within a tumour line between the depression of TFI 4 days after treatment and growth dealy induced by the same treatment. This relationship appears to be independent of the mechanism by which the agent exerts its cytotoxic effect.


Cell kinetics of urethane-induced murine pulmonary adenomas: III. Implications of the disparity between the rates of entry into DNA synthesis and into mitosis.

Metaphase arrest by vincristine in urethane-induced murine pulmonary adenomas became linear after an interval of 60 min. The rate of entry into metaphase was 0-191%/h, which was considerably less than the 1%/h for the rate of entry into DNA synthesis obtained previously by double labelling. The duration of prophase plus metaphase was calculated to be 1-7 h. A growth fraction of 9% and a cell-loss factor of 52% were derived. The disparity between rates of entry into DNA synthesis and into metaphase was investigated by microdensitometry on Feulgen-stained squash preparations of tumours of varying ages. Tne DNA profiles showed an increasing frequency of hyperdiploid nuclei with age. Circumstantial evidence for polyploidy was provided by the presence of many binucleate cells in the tumours. By analogy with the liver, these cells may well represent a stage in the development of polyploidy, and the possible relevance of these findings to the neoplastic process is considered.


Metastasis of a transplantable mammary tumour in rats treated with cyclophosphamide and/or irradiation.

We report observations on the spread by metastasis and infiltration of a transplantable tumour in rats treated by 60Co gamma-irradiation of the primary, irradiation plus parenteral cyclophosphamide, or parenteral cyclophosphamide alone. The proportion of animals with overt disseminated disease and the extent of spread were measured with respect to the time elapsed after implantation and treatment of the primary tumour. The incidence of metastatic disease was broadly similar for all treatment groups, but the extent of dissemination was greater in rats whose treatment included cyclophosphamide.


I-fibrinogen as an oncophilic radiodiagnostic agent: distribution kinetics in tumour-bearing mice.

Fibrinogen radioiodinated by the iodine monochloride method was tested as a tumour radiodiagnostic agent in mice. The I-fibrinogen cleared from the blood of tumour-bearing mice more rapidly than from that of normal mice, but it cleared from the whole body more slowly, suggesting it accumulated in a substantial tumour-related compartment in the abnormal mice. The tumour concentration steadily increased for 4 h after injection, at which time it reached a peak concentration of 11-4% of the injected dose/g. This concentration was higher than the peak concentration for Ga-citrate (not reached until 24 h) or any other oncophilic radiopharmaceutical tested in this tumour model. The early accumulation is consistent with the use of 123I as a tracer label for fibrinogen. A combination of the large tumour concentration of I-fibrinogen, an increased catabolic rate induced by chemical modification, and the exceptional nuclear properties of 123I for scintigraphic imaging, could lead to a very useful radiodiagnostic procedure for cancer.


Nuclear magnetic resonance in cancer, XII: Application of NMR malignancy index to human lung tumours.

Sixty specimens of human lung tissue from 52 individuals were inspected at 22.5 MHz by proton magnetic resonance techniques. The purpose of the study was to evaluate the diagnostic capabilities of the nuclear magnetic resonance (NMR) technique for the diagnosis of malignancy. The combination of two NMR parameters (spin-lattice (T1) and spin-spin (T2) relaxation times) into a malignancy index yielded 3 cases of overlap between the two populations of tissue. The mean and standard deviations obtained were 1.966 +/- 0.262 for normal tissue, and 2.925 +/- 0.864 for malignant specimens. In addition, analysis of the electrolyte and water content of the tissues confirm that factors other than specimen water content influence the relaxation time.


Spectral and metabolic characteristics of mitochondrial fractions from rotenone-induced tumours.

Mitochondrial fractions isolated from tumours induced with the respiratory inhibitor rotenone lack respiratory control, oxidative phosphorylation, are partially or totally insensitive to cyanide and have a near-normal content of respiratory carriers. These characteristics are more similar to those of mitochondria from atrophic mammary gland than to those of mitochondria from spontaneous mammary adenomas. Thus, the characteristic structural and biochemical mitochondrial alteration of rotenone-induced tumours would represent a lack of mitochondrial differentiation as the tumour develops from the atrophic mammary gland. Slices of rotenone-induced tumours are insensitive to oligomycin and dinitrophenol, thus indicating that glycolysis would be their sole source of metabolic energy.


Malignant round-cell tumours of bone: an analytical histological study from the Cancer Research Campaign's bone tumour panel.

A study of 40 cases of malignant round-cell tumour of one was made from the files of the Cancer Research Campaign's Bone Tumour Panel. Five pathologists made a careful study of observer error, involving repeated examination of routine paraffin sections, to determine whether the cases were a homogeneous group or a collection of differing sub-groups. Cell outline, nuclear staining, nuclear pleomorphism, conspicuous nucleoli, reticulin pattern and intracellular glycogen were the histological features selected for study. For each feature, the results were analysed to assess the importance of differences between tumours, between samples of tissue from the same tumour, and between observers. It is concluded that round-cell tumours of bone are a heterogeneous group, although completely distinct sub-groups could not be identified. Certain histological features tend to be associated, and it is reasonable to distinguish on histological grounds between Ewing's sarcoma and reticulum-cell sarcoma, although some tumours are not typical of either group.


Influence of irradiation and chemotherapy on the ovaries of children with abdominal tumours.

The ovaries of children with abdominal tumours were studied in 12 autopsy specimens. Ovaries from 25 children who died in accidents or after a short acute disease served as controls. All ovaries from normal children showed follicle growth, but follicle development was inhibited in 67% of the children with abdominal tumours. The effect of treatment with cytotoxic drugs and/or abdominal irradiation on ovarian morphology was investigated. Normal ovaries were found only in children who had received no chemotherapy or a short course. All patients who had been treated with radiation therapy either alone or in conjunction with chemotherapy had severely damaged ovaries: follicle growth was inhibited in all cases, and the number of small non-growing follicles was markedly reduced in most. It is argued that abdominal irradiation might impair follicle development as well as destroy small follicles.


A combination of chlorambucil, vinblastine, procarbazine and prednisolone for treatment of Hodgkin's disease.

Seventy patients with Hodgkin's disease have been treated with a combination of chlorambucil, vinblastine, procarbazine and prednisolone (Ch1VPP). The complete remission rate of 75-7% compares well with that produced by other combinations. The combination is non-toxic, easily administered and can be given safely to outpatients. Its main advantage is that it is far less upsetting to patients than combinations containing nitrogen mustard.


Thermal injury and the sodium, potassium and water exchanges of skin.

A number of changes in tissue content of Na, K and water are known to occur after injury. In order to elucidate the exact sequence of these changes, experiments were made on explants of guinea-pig flank skin maintained in vitro. This work explores some techniques using explants subjected to graded thermal injury (37 degrees-50 degrees). Stages of increasing damage were identified as higher temperatures were applied and these could be related to the developing changes in cation and water contents. This study is intended to explore a number of possible methods for use in a complete in vitro model to investigate particular problems and events associated with severe trauma.


Coxsackievirus B3 infection in pregnancy and its influence on foetal heart development.

Infection of mice on the 12th or 14th day of pregnancy with Coxsackievirus B3 resulted in the birth of growth-retarded young which died soon after birth and exhibited an abnormal heart development. The ratio of heart weight to body weight in these offspring was higher than normal. The auricles were prominent  and the ventricles developed such that the heart apex was bifid in appearance. This anomalous cardiac development may have been due to a direct viral pathogenicity in the developing tissue or, as seems more likely, resulted from a generalized disturbance in foetal growth attributable to a virus-induced pancreatic insufficiency in the mother. Retarded development in the pulmonary system also resulting from aberrations in foetal growth may have been contributory to impaired postnatal cardiac growth.


Effect of partial portal vein ligation on immune glomerular deposits in Schistosoma mansoni-infected mice.

Portosystemic collateral circulation was induced in mice infected or not with Schistosoma mansoni by partial ligation of the portal vein. The effects on immune glomerular deposits were assessed and compared to findings in unoperated infected, sham-operated and normal animals. Mesangial immune deposits of IgM, IgA, IgG and C3 were found by immunofluorescence significantly more frequently in operated than in unoperated infected mice. Schistosomal antigen was demonstrated in 5 animals out of 38 infected ones, 4 of the 5 having been operated. The results suggest that portosystemic collateral circulation might be an important factor in the genesis of schistosomal glomerulopathy, perhaps by diversion of antigens or complexes from the Kupffer cells. The high percentage of glomerular immune deposits found in uninfected ligated animals (71-4%) suggests furthermore that non-specific immune factors possibly of intestinal origin could be involved.


The effect of anti-lipolytic agents on isoprenaline-induced myocardial necrosis in the rat.

The effect of inhibiting isoprenaline-induced lipolysis on the degree of damage produced in the rat myocardium by this amine has been investigated by pre-dosing rats with the anti-lipolytic agent 5-fluoro-nicotinic acid. The degree of myocardial necrosis produced in animals given isoprenaline alone and those pre-dosed with the anti-lipolytic agent was measured by the use of an automated flying spot microscope to show absence of formazan from dead muscle fibres in sections treated to demonstrate succinic dehydrogenase. The use of the anti-lipolitic considerably reduced the degree of myocardial damage produced by a standard dose of isoprenaline bitartrate. This was associated with an inhibition of the post-isoprenaline rise in plasma free fatty acid levels. The results are discussed in relation to the possible protective roles of the lowering of plasma free fatty acid levels and inhibition of the adenyl cyclase system at the plasma membrane of the myocardial cell produced directly by the anti-lipolytic.


Photochemotherapy for pustular psoriasis (von Zumbusch).

Photochemotherapy (PUVA) with oral methoxsalen and UV-A was instituted in 8 patients with generalized pustular psoriasis (von Zumbusch). Complete clearing of skin lesions and of systemic symptoms was achieved in all patients. Patients who had been on systemic treatment prior to PUVA had to be treated with considerably more UV-A energy than patients who had received topical therapy alone. Seven patients were kept in complete remission by maintenance therapy for an observation period of up to 1 1/2 years. Side effects of systemic pre-PUVA treatment resolved during several months of maintenance therapy.


A dosimeter for long wave ultraviolet radiation.

A polymer film, which incorporates phenothiazine as the chromophore, has been developed as a personnel dosimeter for long wave ultraviolet radiation. It is stable, reproducible and is particularly suited to monitoring the doses received by patients undergoing photochemotherapy for psoriasis.


Histological findings in clinically normal palmar skin of patients with psoriasis.

Light microscopy was used to examine the clinically normal palmar skin of 18 psoriatic patients (10 inactive and 8 active) and 18 non-psoriatic control patients. Histological changes in both epidermis and dermis vary with activity of the disease. The findings support the view that defective keratin formation precedes excessive proliferation of epidermal cells.


Thin-layer chromatography of phospholipid components of normal and psoriatic epidermis.

The phospholipid pattern of human epidermis from 23 psoriatic patients and from 14 healthy individuals has been determined using lipid thin-layer chromatography. An increased amount of total phospholipids and statistically significant differences in some phospholipid components were found in psoriatic patients as compared to healthy controls. These abnormalities may be related to the altered architecture of the plasma membranes and their surface coats observed in psoriatic keratinocytes.


Incorporation of I-14C-acetate into epidermal lipids. A comparison between isolated epidermal cells and epidermal slices.

Suspensions of pig epidermal cells were prepared by trypsinisation of epidermis and incubated with I-14C-acetate in Eagle's minimum essential medium containing 10% serum. The incorporation of radioactivity into the total lipids of the cells increased with time despite the decrease in the proportion of viable cells which occurred during the period of incubation. The pattern of incorporation into the phospholipids and glycolipids showed similar changes with time to those observed previously with rat epidermal cell suspensions. Pig epidermal slices were incubated with I-14C-acetate in Eagle's minimum essential medium in the presence and absence of 10% serum. The proportion of radioactivity incorporated into the polar lipids was much greater in the epidermal slices than in the suspensions of epidermal cells. The pattern of incorporation in the phospholipids and glycolipids of epidermal slices differed from that found with epidermal cell suspensions and the pattern did not alter so markedly with the time of incubation. However, in each case reproducible patterns of incorporation were obtained under controlled conditions. The method of analysis can therefore be used to study lipid changes in small biopsies of normal and pathological skin.


5-Hydroxytryptamine and tryptamine pathways in scleroderma.

Levels of 5-hydroxyindoleacetic acid, indoleacetic acid and total indoles were determined in the urine of 23 patients with systemic scleroderma and 7 patients with cutaneous scleroderma, before and after peroral loading with L-tryptophan (0-1 g/kg body weight). Before loading, 5-hydroxyindoleacetic acid levels were normal in nearly all cases of systemic scleroderma as well as of cutaneous scleroderma; however after loading, in nearly one half of cases there was no normal increase of this metabolite. These results suggest impaired transformation of serotonin into 5-hydroxyindoleacetic acid. A disproportionately high ratio of total indoles to indoleacetic acid suggests the presence of excess of tryptamine. The results of the study may indicate that in scleroderma metabolism of biogenic amines derived from tryptophan is abnormal, probably as a result of impaired activity of monoamine oxidase.


Amyloid production by dermal fibroblasts. Electron microscopic studies on the origin of amyloid in various dermatoses and skin tumours.

Electron microscopic investigations in 7 patients with different dermatoses or skin tumours containing amyloid showed that amyloid is synthesized in the cytoplasm of dermal cells. In 3 cases of localized primary amyloidosis of the skin highly active cells were demonstrated, showing grossly dilated cisternae of rough endoplasmic reticulum, resembling fibroblasts. Their intracellular product seemed amorphous, later filamentous, and was then released into the extracellular space. Extracellular aggregations of typical amyloid filaments were found partially surrounded by thin cytoplasmic remnants of the cells producing them. Subclinical amounts of amyloid found in porokeratosis of Mibelli, in superficial basal-cell carcinoma, in senile skin, and in clinically normal skin of a patient with malignant melanoma showed the same characteristics. Other cell types such as plasma cells and mast cells were well preserved and seemed stimulated; however, no amyloid precursors were found in their cytoplasm and no release was seen. We, therefore, conclude that dermal amyloid is generally produced by falsely programmed fibroblasts.


The wages of warmth: changes in erythema ab igne.

Biopsies from 20 patients with erythema ab igne (EAI) were examined and compared with biopsies from the legs of 7 elderly control subjects. Epidermal thinning and flattening of the dermo-epidermal junction were seen in most of the tissues examined but were more prominent in the EAI biopsies. Basal cell degenerative change with vacuolation was frequently observed in the EAI specimens. Epidermal atypia amounting to preneoplastic change was observed in 4 EAI biopsies. The dermis was thinned and showed (a) marked oedema and connective tissue disruption and (b) accumulation of elastic staining material. Both haemosiderin and melanin were found within the dermis. The small blood vessels showed a striking abnormality in 7 patients and 2 control biopsies in that the endothelial cells were enlarged and the nuclei were hyperchromatic and irregular in size and shape. This change may be due more to stasis than to chronic heating.


Evaluation of crew skin flora under conditions of a full quarantine lunar-exploration mission.

Crew-members of the Apollo 14 lunar exploration mission underwent a pre-flight seclusion designed to stabilize their health by freeing them from exposure to potentially infectious agents. After the flight, the crew-members were quarantined to protect the biosphere from possible lunar contamination. These isolations, along with the complete isolation of the spaceflight itself, provided the opportunity for a skin flora survey which included the sampling of seven sites at five different times. Quantification and identification of all aerobic and anaerobic bacteria from each site were performed. The results indicated that the pre-flight quarantine measures resulted in a decrease in total numbers of isolates as well as a decrease in the anaerobes. This was followed by a continued decrease throughout the flight with a return to the pre-flight norm within 16 days after the flight. The quantitative load of aerobic bacteria increased during the flight, due largely to an increase in coryneforms and micrococcaceae. The quantitative load of anaerobic bacteria decreased before and during the flight. No instance of microbial shock or intercrew transfer of micro-organisms was demonstrated. These findings indicate that alterations in the skin flora do not pose any unusual problem during short duration space flights. Further, there are no indications that problems will arise on longer missions.


Antibodies to UV DNA and photosensitivity.

Antibodies to ultraviolet light denatured DNA (UV DNA) have been measured in the sera of patients with systemic lupus erythematosus, discoid lupus erythematosus, and light sensitive skin lesions. Antibodies were found in significant levels in the patients with SLE but not in the other groups. It appears that although UV denaturation of dermal DNA occurs in vivo this is not sufficient to induce antibodies to UV DNA in patients with a normal DNA repair mechanism. This may not be the case in patients with SLE in whom a break in tolerance to Native (N-) DNA has already occurred and where antibody to N-DNA will cross react with UV DNA.


Ascorbic acid and melanogenesis.

The ascorbic acid contents of skin, plasma and urine were estimated in 12 vitiligo cases, one albino and 10 normal subjects. All the estimations were repeated after saturation with ascorbic acid. There was no difference between the two groups with regard to the ascorbic acid contents of their plasma or urine. The ascorbic acid level of vitiliginous skin was decreased; however, this difference just falls short of significance at the level P = 0-05. Further investigations with a larger group of patients are indicated.


Cutaneous sarcoidosis treated with methotrexate.

Sixteen patients with cutaneous sarcoidosis, 15 of whom also had involvement of other organs, were treated with methotrexate (MTX) orally once a week in an open study. The treatment period was from 1 to 72 months (mean 23 months). In 12 patients the skin lesions cleared, and in 3 of 4 patients who had sarcoid uveitis this cleared as well. The chest X-ray of 6 patients showed no corresponding improvement in pulmonary changes or in hilar adenopathy. Ten patients suffered side effects, usually nausea on the day MTX was taken. Two had transiently increased transaminase levels. Treatment was discontinued in 2 patients due to nausea. It is concluded that MTX is a useful alternative to systemically administered glucocorticoids in the treatment of disfiguring cutaneous sarcoidosis and sarcoid uveitis. The effect of MTX on hilar adenopathy and pulmonary sarcoidosis is uncertain.


Factitious skin lesions in a mother and two sons.

A family is described in which a woman, probably in a state of 'hysterical conversion', produced factitious lesions in her own skin (dermatitis artefacta) and in the skin of two sons (child abuse). Non-accidental injury to a child's skin may form part of a spectrum of skin artefacts in the parent.


Cutaneous infection by Cryptococcus laurentii.

Cryptococcus laurentii was isolated twice from cutaneous granulomas in the leg and foot of a 40-year-old man. Histologically the cells of C. laurentii were found in groups in the dermis and also inside giant cells. There was epithelioid cell infiltration in the dermis and subcutis. An atypical mycobacterium was isolated in addition to C. laurentii. Therapy with anti-tuberculous drugs after an initial amphotericin B infusion was found to be satisfactory.


A mortality study among workers in an English asbestos factory.

The previous report on this cohort study of workers in an asbestos textile factory (Knox et al., 1968) showed little evidence of increased mortality among workers who had entered the factory after the implementation in 1932 of the first Asbestos Industry Regulation (1931) but observed that no firm conclusions could be drawn, as little carcinogenic effect would be expected for 20 years after first exposure. A further 8 1/2 years of follow-up has revealed some asbestos-related disease in this latter group, although very much less than for employees first exposed before 1933. Among the 963 workers first exposed in 1933 or later, mortality was increased for carcinoma of the bronchus (31 deaths; 19-3 expected for all lung cancers) and non-malignant respiratory disease (35 deaths, 25-0 expected), and a further 5 deaths were attributed to pleural mesothelioma.


Insulation workers in Belfast. A further study of mortality due to asbestos exposure (1940-75).

A follow-up study of 162 men already working as insulators (laggers) in 1940 has been extended from 1965 to 1975. By the end of 1975 there were 40 survivors when 108 had been expected. Until 1965 there had been an overall excess of deaths; these were due to asbestosis with or without tuberculosis and to alimentary cancer, as well as to bronchial carcinoma and mesothelioma. From 1965 onwards the overall death rate among survivors is not so excessive but there is still a marked excess of deaths from bronchial cancer and mesothelioma. The continued risk of death attributable to malignancy after asbestosis had ceased to contribute directly, does not appear to be caused by any changes which occurred before 1940 in the conditions at work.


An investigation into the health of kapok workers.

Kapok is a cotton-like fibre obtained from the fruits of Ceiba pentandra, a tree surgeon in tropical countries. In Sri Lanka ginning of kapok is usually done by machine in poorly ventilated buildings where workers are exposed to a great deal of dust. Forty-one workers in five ginneries in Colombo were examined. Mill fever occurred in 28 (77-8%) of the 36 workers who were able to give a history. Chronic bronchitis, which is an uncommon condition in Sri Lanka, was detected to seven workers with an average of 20-9 years' service in the industry. It is suggested that chronic bronchitis is an occupational hazard of workers who are exposed to kapok dust for long periods. Byssinosis was not found in any of the workers studied.