Bone mineral content and estimated total body calcium in normal children and adolescents. Bone mineral content in the distal part of the forearm was measured in 301 normal children and adolescents aged from 7-20 years to estimate total body calcium in these age groups. From year 7 to 9 and from year 15 to 20 the mean values in boys were significantly higher than those in girls. In the lower age groups there was a slow increase in estimated total body calcium with age, followed by a sharp increase at the age of puberty.


Determination of fractional renal function in renography with and without individually [131I]albumin-determined blood background. Fractional renal function was determined from 122 renographies using three different blood background subtractions: with individually [131I]albumin-determined correction factors, with direct subtraction of the thorax background curve. In the latter case a systematic error was introduced, since the right kidney's fractional function was overestimated and that of the left kidney accordingly underestimated. With mean correction factors the deviation from 'true' fractional function (as determined individually with [131I]albumin) was negligible. We recommend this principle since it is simple and sufficiently accurate.


A scintillation camera technique for quantitative estimation of separate kidney function and its use before nephrectomy. A scintillation camera technique was used for measuring renal uptake of [131I]Hippuran 80-110 s after injection. Externally measured Hippuran uptake was markedly influenced by kidney depth, which was measured by lateral-view image after injection of [99mTc]iron ascorbic acid complex or [197Hg]chlormerodrine. When one kidney was nearer to the dorsal surface of the body than the other, it was necessary to correct the externally measured Hippuran uptake for kidney depth to obtain reliable information on the true partition of Hippuran between the two kidneys. In some patients the glomerular filtration rate (GFR) was measured before and after nephrectomy. Measured postoperative GFR was compared with preoperatively predicted GFR, which was calculated by multiplying the preoperative Hippuran uptake of the kidney to be left in situ, as a fraction of the preoperative Hippuran uptake of both kidneys, by the measured preoperative GFR. The measured postoperative GFR was usually moderately higher than the preoperatively predicted GFR. The difference could be explained by a postoperative compensatory increase in function of the remaining kidney. Thus, the present method offers a possibility of estimating separate kidney function without arterial or ureteric catheterization.


Work capacity, muscle strength and SDH activity in both legs of hemiparetic patients and patients with Parkinson's disease. In recent muscle metabolic studies, patients with moderate upper motor neuron lesions showed marked difficulty in performing an equal submaximal work load (bilaterally) in two-legged exercise. For a better evaluation of these patients, studies were performed on each leg separately. Six patients with Parkinson's disease and six with moderate hemiparesis were studied. During one-legged submaximal and maximal exercise heart rate, oxygen uptake, and blood lactate were determined. Maximal voluntary contraction in knee and ankle flexion and extension for each leg was measured. Succinate dehydrogenase (SDH) activity in the thigh muscles was determined. During  submaximal exercise, oxygen uptake, heart rate and blood lactate increased more in the paretic leg of hemiparetic patients and in the more affected leg of the Parkinson patients. In hemiparetic patients maximal voluntary contraction of flexors and extensors of the knee was significantly reduced in the paretic leg but was reduced even in the nonparetic knee flexors. SDH activity was very low in both legs in all patients and lowest in the paretic and more affected leg, respectively. It is concluded that (a) the general muscle inactivity per se, secondary to the neurological disorder, may lead to a reduced work capacity; (b) the increased heart rate and blood lactate level seem to be correlated to the relative exercise level of each leg; and (c) in patients with impaired muscle function of one or both legs, evaluation of each leg separately with regard to work capacity and muscle metabolism is of value.


Temperature of mixed venous blood during exercise. The temperature of mixed venous blood (PA-temp) was measured in the pulmonary artery of healthy male volunteers at rest and during bicycle exercise in the supine position. Oxygen uptake, arteriovenous oxygen difference, and heart rate were determined simultaneously. The subjects were studied both in their basal normokinetic circulatory state and in a hypokinetic circulatory state induced by beta-receptor blockade with propranolol. The PA-temp increased linearly with rising oxygen uptake. During beta-receptor blockade the exercise-induced rise in PA-temp was considerably steeper in relation to work load and to oxygen uptake. Thus when the ordinary ability to increase cardiac output was suppressed by propranolol, an identical dynamic exercise induced a significantly higher PA-temp. A significant correlation (r = 0.92) was found between the rise in PA-temp during exercise and the increase in the arteriovenous oxygen difference. This correlation, which has not been described previously, was not altered by beta-receptor blockade. It is concluded that the close correlation between blood temperature and arteriovenous oxygen difference has a clinical potential for hemodynamic measurements. A simple method for the indirect estimation of arteriovenous oxygen difference by means of blood thermometry would be a considerable laboratory advantage.


Available bilirubin binding sites of serum from newborns determined by a direct spectrometric method using bromphenol blue. A new direct spectrometric micromethod for the determination of the available bilirubin binding sites of serum (S-ABBS) using bromphenol blue has been applied to 298 blood specimens collected from infants immediately before starting the first exchange transfusion. A relative number fraction of 0.07 of the material, characterized by having the lowest S-ABBS values, includes seven of the nine cases (i.e. a relative number fraction of 0.78) with autoptically verified kernicterus (KI). The two infants with KI but higher S-ABBS values differed in having severe neurological symptoms before the examination. The mean substance concentration of bilirubin in these nine sera was 288 mumol/l. The correlation of KI to the body mass at birth, to the substance concentration of serum albumin, and to the substance concentration of serum bilirubin is given, and the sources of error concerning the method are discussed. The present method is proposed for determining a type of quantity that is important, among other types of data, in deciding on the need for exchange transfusion in icteric (premature) newborns.


Characterization and significance of collagen induced biphasic aggregation of human platelets. Biphasic collagen-induced platelet aggregation, resembling that induced by epinephrine, was noted in platelet-rich plasma (PRP) of 11 stroke and 1 coronary disease patients. Similar pattern of aggregation was not observed in normal PRP. The occurrence of the biphasic collagen aggregation does not appear to relate to platelet count, smoking habit, medication, or other abnormalities such as hypertension, diabetes, and elevated serum lipid levels. However, platelets of these patients were very sensitive to aggregating agents including epinephrine and adenosine diphosphate. The concentration of collagen that elicited biphasic aggregation in these platelets was too weak to aggregate platelets of normal subjects. We believe that the release threshold of these platelets is reduced to such an extent that minute amounts of collagen, which would be insufficient to induce release from normal platelets, are capable of inducing release from these platelets. Both phases of collagen induced aggregation are probably resulted from the activation of the release mechanism.


Amino acid concentrations in plasma and erythrocytes in aregeneratory and haemolytic anaemias. The concentrations of unbound amino acids in erythrocytes and in plasma from 7 normal individuals, 11 patients with various types of aregeneratory anaemia, and 4 patients with hereditary haemolytic anaemias were determined on a Technicon Amino Acid Analyzer (Perry et al 1970). Most amino acids were normally found in higher concentrations in plasma than intracellularly. Cystine, methionine and trypotophan were almost exclusively present in plasma. Aspartic acid, however, was mainly found in erythrocytes, and glutathione only in erythrocytes. Glutamic acid and ornithine were more concentrated in the cells, while glycine and asparagine showed approximately the same concentrations in erythrocytes as in plasma. In the patients, plasma amino acids showed little deviations from normal, but in the erythrocytes there were striking changes. Erythrocyte glutamic acid concentrations were moderately to markedly elevated in all patients studied, and glycine concentrations in 13 out of 15 patients. In addition, the following amino acids were increased intracellularly in more than one patient: glutamine (8 patients), serine (7), asparagine (5), threonine (4), taurine (3), alanine (2), valine (2), ornithine (2), lysine (2), citrulline (2). Aspartic acid was decreased in erythrocytes from 4 patients with aregeneratory and 1 with haemolytic anaemia.


Cytogenetic differences between bone marrow and spleen in a case of agnogenic myeloid metaplasia developing blast crisis. Chromosome studies of cells from bone marrow and spleen were performed in a patient with agnogenic myeloid metaplasia (MM) developing blast crisis after a chronic phase lasting for 6.5 years. The proportions of blast cells were roughly the same in bone marrow and spleen. In the bone marrow 43 % of the metaphases were abnormal with a marker chromosome whereas all spleen metaphases were normal. The results indicate that chromosomal changes associated with blast transformation in MM may occur in the bone marrow prior to such changes in the spleen and support the concept that bone marrow and spleen may constitute relatively separate pools of haemopoietic tissue in chronic myeloproliferative diseases.


A positive ethanol gelation test associated with high plasma fibrinogen concentration - evidence for soluble fibrin. An experimental study in rabbits. By infusion of large amounts of human fibrinogen into rabbits, the ethanol gelation test turned positive at various plasma concentrations of fibrinogen, depending on the fibrinogen preparation used, and on individual differences among the animals. After incubation of the fibrinogen preparation in the cold the precipitated material gave a positive ethanol gelation test at lower fibrinogen concentration whereas the ethanol gelation test remained negative in the supernatant at a higher fibrinogen level than that of the starting material. It is concluded that the finding of a positive ethanol gelation test is not due to the fibrinogen concentration per se. Most likely the test becomes positive due to the presence of soluble fibrin in the commercial preparations.


Karyotypes in infectious mononucleosis.

Karyotypes in infectious mononucleosis. Using a trypsin-Giemsa banding procedure, chromosome analysis was performed on blood from 21 consecutive patients hospitalized for infectious mononucleosis. Mitoses were harvested after 2 and 24 h in vitro incubation without PHA and after 48 h with PHA. No abnormalities were seen.


Death of blood lymphocytes studied by supravital dye exclusion and 3H-thymidine-autoradiography. Lymphocyte death in peripheral blood of the mouse represents the death of both short- and long-lived lymphocytes. The present data were based on lymphocyte separation, supravital dye exclusion, and autoradiographical procedures. The data strongly indicate that the frequency of intravascular cell death in the population of short-lived lymphocytes is 4-10 times higher than the frequency of intravascular cell death of long-lived lymphocytes.


Congenital dyserythropoietic anaemia with peculiar nuclear abnormality. A patient with clinical and haematological findings compatible with congenital dyserythropoietic anaemia (CDA) most porbably type II is described. In contradistinction to previous observations, electron microscope examination of the erythroid cells in the bone marrow showed the concomitant appearance of nuclei at different maturation stages in a single cell. In addition, a marked tendency toward multinuclearity of the megakaryocytes was found. The mature erythroblasts showed an increased uptake of 3H-thymidine less than is normally found in these cells. Thes findings suggest an impairment in RNA and DNA synthesis.


Congenital dyserythropoietic anaemia with features of both type I and TYPE II. A 13 year old girl with the typical clinical and haematological picture of congenital dyserythropoietic anaemia (CDA) is reported. The bone marrow is highly cellular with 70 per cent erythroid cells, and 28% bi- and multinuclear cells among the orthochromatic and polychromatic erythroblasts. Moderate megaloblastoid changes are present. On light microscopy the findings are in agreement with those described in CDA type II. On electron microscopy both the cytoplasmatic changes described as typical of CDA type II, and the nuclear changes found in type I can be demonstrated. The acidified serum test (Ham test) is negative with normal sera. The patient's red blood cells show increased agglutinability with anti-I and and anti-I antibodies, but no haemolysis. Total serum lipids are about 50% of the normal average. All lipoprotein classes are lowered to about the same extent. The total phospholipid content of the erythrocytes is slightly reduced, with a moderate, relative increase of the lecithin fraction and a decrease of the sphingomyelin fraction. Doubts can be raised about the tenability of the current classification of CDA based on morphological and serological criteria, especially about the distinction between types I and II.


Mechanism of anaemia in experimental bacterial endocarditis. Rabits with Streptococcus viridans aortic valve endocarditis develop anaemia and reticulocytosis which increase with the duration of infection. Mean red cell counts decreased from 6.05 +/- 0.29 X 10(6) per mul before infection to 4.10 +/- 0.18 X 10(6) per mul after 11 to 20 days of endocarditis and reticulocytes increased from 1.16 +/- 0.14 X 10(5) per mul to 4.91 +/- 0.83 X 10(5) per mul after more than 20 days of endocarditis. The anaemia could not be explained by intravascular haemolysis. Anti-erythrocyte antibodies were not detected. Splenomegaly was a consistent finding and also increased with the duration of infection. Red cell half life (T1/2) was shortened to 4.7 +/- 0.3 days in rabbits with endocarditis compared with normal T1/2 of 11.1 +/- 0.5 days. The T1/2 of red cells from infected animals was prolonged when measured in noninfected rabbits and splenectomized animals had a mean red cell T1/2 of 9.25 days after three weeks of infection. These studies suggest that splenic enlargement associated with infection results in red cell sequestration, a mechanism not well recognized as contributing to the anaemia of endocarditis.


Immunoglobulin synthesis in vitro by cerebrospinal fluid cells in patients with meningoencephalitis of presumed viral origin. Cerebrospinal fluid (CSF) cells from six patients with meningoencephalitis of presumed viral origin were incubated in the presence of labeled amino acids. The cells of two of the patients synthesized IgG, IgA, and IgM (one patient) in vitro. The CSF of these two patients had an elevated level of IgG with oligoclonal distribution. The newly synthesized IgG also had an oligoclonal distribution. CSF cells of the other four patients were not shown to synthesize immunoglobulins in vitro. The CSF of these patients had a normal level of IgG with polyclonal distribution. The results demonstrate that in some patients with virus meningoencephalitis an immunoglobulin synthesis takes place locally and that at least part of the IgG shows a restricted heterogeneity. The results also suggest the presence of stimulated lymphocytes in the CSF of the same patients.


Detection of IgG aggregates or immune complexes using solid-phase C1q and protein A-rich Staphylococcus aureus as an indicator system. A radioimmunoassay for detection of C1q-binding IgG aggregates and antigen-IgG antibody complexes is described. The assay makes use of solid-phase C1q and 32p-labelled protein A-rich Staphylococcus aureus as an indicator system. Both 19S and heavier IgG aggregates that fixed C1q were detected. The sensitivity of the assay permitted detection of heavy (19-25S) IgG aggregates at a concentration of 8 mug/ml or less. The results indicated that detection of IgG in this assay is dependent on the degree of IgG polymerization and the molar ratio between the solid-phase C1q and the IgG polymers. Albumin-anti-albumin complexes, preformed at equilibrium with antibody to antigen molar ratios of 2:1 to 3:1 and at antigen concentrations of 25 to 40 mug/ml, were also detectable using the described radioimmunoassay.


A solid-phase radioimmunoassay for C1q-binding immune complexes. I. Delta IgG as indicator molecule. A solid-phase radioimmunoassay for detection of circulating C1q-binding immune complexes (IC) or heat-aggregated IgG (delta IgG) is described. Purified human C1q protein was adsorbed to a fixed area of polystyrene tube surface for 1 hr at 22 degrees C, pH 7.3, mu 0.15. Binding of delta IgG or IC to solid-phase C1q at 22 degrees C progressed over several hours and was enhanced at low mu (0.05). Heating of C1q (56 degrees C for 30 min) reduced the binding by 85%-90%. Binding of IC or delta IgG was retained after several weeks' storage of solid-phase C1q at 4 degrees C. Detection of 2-5 ng delta IgG and less than 50 ng IC (in antibody excess) was achieved in competitive binding or inhibition tests with [125I]delta IgG. Preliminary testing of 48 human sera indicated the usefulness of the assay for detection of IC in patient sera.


Fc receptors in human placenta.

Fc receptors in human placenta. Cryostat sections of placental tissue strongly adsorbed erythrocytes sensitized with IgG antibodies of human, rabbit, and guinea pig origin. No adsorption occurred using erythrocytes sensitized with F(ab')2 fragments. The reaction was strongly inhibited by intact IgG and by Fc fragments, weakly inhibited by pFc' fragments, and not inhibited by Facb and F(ab')2 or albumin. These properties are similar to those of corresponding receptors in normal lymphoid tissues. Results obtained with sections of hydatidiform mole showed that the reaction occurred with the trophoblastic tissue. Porcine placenta had no Fc receptor activity. The presence of an Fc receptor in human placental tissue may therefore be of significance for the selective transfer of IgG from mother to foetus.


The natural history of the frozen shoulder syndrome. A prospective study has been made of 49 patients with the frozen shoulder syndrome (as distinct from tendinitis, calcific deposits and frozen shoulders occurring after coronary infarction or with pulmonary tuberculosis) of whom forty-one have been followed up for 5-10 years, always to their greatest recovery. There were three consecutive stages: pain, stiffness, and recovery. The stiffness stage was usually related to the duration of the recovery stage. The total duration was longer than is generally supposed (an average total of 30.1 months in contrast to about 18 months as often postulated). Generally speaking, the longer the stiffness stage is, the longer is the recovery stage. In 4 patients the second shoulder became similarly affected, 6 months to 7 years after the first, and followed a similar chronological sequence to the first. After greatest recovery, slight restriction of movement was found in more than half the cases, but in only 3, all of long duration, was the restriction a handicap. Arthrography, carried out on both shoulders in all patients during the recovery stage, showed in the affected shoulder fewer rotator cuff defects than expected at this age and fewer (four) than in the contralateral one (twenty-three); seemingly, the condition leads to the obliteration of some defects.


Ultrastructural and histochemical studies of muscle in rheumatoid arthritis. Muscle biopsy material from 12 patients with rheumatoid arthritis was investigated by electron microscopy. Degenerative changes and atrophy of the muscle fibres were observed. The periphery of the fibre was indistinct and showed an increased content of lipofuscin granules and remnants of myofilaments. Mitochondria were frequent in the subsarcolemmal regions, but between the myofibrils these were rarer than in healthy subjects. The triads were often swollen and displaced. Capillaries were more frequent than in normal material; the endothelial cells and especially the basement membrane showed pathological changes. Satellite cells were frequent and are regarded as an indication of regeneration.


Death rate and causes of death in patients with rheumatoid arthritis. Patients with rheumatoid arthritis, 500 males and 500 females, aged 40 years or over, and an age- and sex-matched control population were observed over a 3-year period. During the follow-up, 122 RA patients and 69 controls had died. The most common causes of death in RA patients were cardiovascular diseases (57 patients), renal failure (27 patients), infections (19 patients), and malignant neoplasms (11 patients); in the controls, the respective data are: cardiovascular diseases (35 people), malignant neoplasms (21 people), accidents (7 people), and infections (5 people).


Generalised and localised bone loss in patients with rheumatoid arthritis. Osteoporosis was studied in 307 patients with "definite" or "classical" rheumatoid arthritis by measurement of the clavicular cortical thickness (C.C.T.). Bone loss, as measured by this index, fell with advancing age, and was significantly greater than in non-rheumatoid control subjects matched for age and sex. Bone loss from the clavicles was not greater in patients treated with corticosteroid drugs. Loss of bone from the clavicle correlated with osteoporosis in other parts of the skeleton, as determined by the femoral and metacarpal indices. This suggests that osteoporosis in rheumatoid arthritis is a generalised phenomenon rather than a localised process secondary to adjacent joint inflammation.


Questionable effects of Myocrisin in experimental arthritis in rabbits. In 18 rabbits arthritis was induced in one knee joint by injection with 0.2 ml 3% ovalbumin 4 weeks after sensitization by 3% ovalbumin and 2 mg/ml tubercle bacilli suspended in Freunds incomplete adjuvant. Half of the rabbits were treated with Myocrisin 4 mg i.m. once a week during the experimental period lasting 4-5 months. At killing, both knee joints were examined macroscopically and microscopically. In all rabbits a distinct synovitis was found in the injected knee joint. Histologically, the changes were most pronounced in the rabbits not treated with Myocrisin. An activity index of the synovial membrane changes in the Myocrisin-treated and untreated cases was calculated to 6.3 and 3.6 respectively. Some changes were also found in the uninjected knee joints of 50% of the rabbits. In contrast to some other works, this preliminary investigation suggests that antigen-induced experimental arthritis is suppressed by gold. We feel that this model of experimental arthritis may be suitable for trying out the effect of various drugs.


A comparative study of the protein pattern in serum and synovial fluid. A routine program for evaluation of the protein pattern in serum and synovial fluid has been tested on 25 patients in a consecutive study. The program comprised agar gel electrophoresis, total protein and albumin determination, and immunochemical determination of antitrypsin, orosomucoid, haptoglobin, IgR, and IgA. Linear correlation analysis of corresponding data in serum and synovial fluid gave r-values for the five latter components which varied from 0.74 to 0.87. On this basis reference intervals in synovial fluid could be established. Total protein, haptoglobin and IgG were elevated in rheumatoid arthritis, compared with osteoarthritis.


Renal glomerular function in ankylosing spondylitis. From a study of 38 consecutive patients with ankylosing spondylitis (AS) it is concluded that impairment of renal glomerular function is not seen, despite the recognised pathological changes.


Zinc: its relationship to osteoporosis in rheumatoid arthritis. Preliminary studies indicate that plasma zinc concentrations, as estimated by atomic absorption spectrophotometry, are reduced in rheumatoid arthritis. A relationship has also been established between metacarpal index of osteoporosis and plasma zinc concentrations in rheumatoid subjects.


Dosage of salicylates for children with juvenile rheumatoid arthritis. A preliminary report. The daily dosage of salicylates is traditionally very high for patients with juvenile rheumatoid arthritis. In order to achieve the optimal therapeutic effect, serum salicylate levels are kept at 30-35 mg/100 ml (2175-2540 mumol/l). The recommended daily dosage in the textbooks is about 100 mg/kg of body weight, and the reported dosage/m2 of body surface area has been 3.2 g/m2/day. These dosages are, however, too high in clinical routine. In the present investigation, 19 children were treated with salicylates for 15 days with daily check-ups of the serum salicylate levels. Seven of these children had symptoms of salicylate intoxication which corresponded closely to the serum salicylate levels. If the daily dosage of salicylates exceeds 3 g/m2 of body surface area, intoxication can be expected.


Bacteriological findings in transtracheal aspirates from patients with chronic bronchitis and bronchiectasis: a preliminary report. Thirty-six transtracheal aspirates from 34 patients with chronic bronchitis and bronchiectasis were examined bacteriologically. Bacteria were isolated from 30 aspirates, 23 of which yielded pure culture. Anaerobic bacteria were found in three aspirates, all in pure culture. This preliminary report indicates a greater complexity of the microbial flora in chronic bronchitis and bronchiectasis than hitherto appreciated.


Pulmonary lesions and autoimmune reactions after long-term nitrofurantoin treatment. Hypersensitivity reactions in two women with pulmonary lesions, autoimmune reactions with positive antinuclear factor and liver damage following long-term nitrofurantoin treatment are discussed. One patient had taken nitrofurantoin for more than 1 year and the other for more than 2 when their symptoms appeared. They were in a very poor condition, but recovered when the drug was withdrawn. Lymphocyte transformation test in vitro showed significant blast-transformation, indicating the involvement of immunological mechanisms. Treatment with corticosteroids had not been instituted.


Effects of practolol in combination with terbutaline in the treatment of hypertension and arrhythmias in asthmatic patients. After a run-in period practolol was given in the dose of 100 mg twice daily to 29 patients with chronic bronchial asthma on the indication hypertension (12) and supraventricular arrhythmia (17). During the run-in period, as well as during the practolol period, a long-acting beta2-stimulator, terbutaline, was given in the dose of 5 mg three times daily. Peak expiratory flow (PEF), heart rate and blood pressure were measured under standardized conditions. No change of the lung function was observed during practolol therapy. Systolic as well as diastolic blood pressure fell significantly. The heart rhythm was normalized in 15 of the arrhythmic subjects. No subjective worsening of the asthmatic symptoms or any other side effects were noted. It is suggested that practolol can be safely used in patients prone to bronchospasm, provided a long-acting beta2-stimulating drug is given concomitantly on the usual indications for beta blockers in acute situations.


Predominantly unilateral asthma studied with 133Xe-radiospirometry. Regional lung function in the supine position was studied with 133Xe-radiospirometry in 10 asthmatic subjects in remission, before and after inhalation of specific allergens in the right lateral decubitus position. Regional ventilation and regional lung volume showed a significant decrease in the right lung. The decrease in ventilation was most pronounced in the diaphragmatic half of the lung. The regional perfusion of the right lung decreased less than the ventilation. The change in perfusion, however, became greater with time, whereas the decrease in ventilation remained the same as shortly after the provocation. Predominantly regional asthma could thus be provoked in the regions that receive most of the allergen in the right lateral position. The asthma was easily controlled and caused little discomfort.


Spleen cells transmit osteopetrosis in mice. Osteopetrosis was induced in lethally irradiated, normal mice of grey-lethal and microphthalmic stocks by cell infusions prepared from the spleens of osteopetrotic littermates. Failure of skeletal remodeling became evident within a few weeks after transplantation as calcified cartilage and bone accumulated excessively in the active metaphyses of the long bones. The massive lesions produced were extensively infiltrated with abnormal osteoclasts.


The quantitative relations between diffusion-controlled reaction rate and characteristic parameters in enzyme-substrate reactions systems. II. Charged substrates. The quantitative relationship between the spatial factor and the force-range factor on the one hand and the ionic strength and the charges of reactants on the other has been calculated for non-spherically symmetric reaction systems. New upper limits of combination reactions between enzymes and charged substrates have been obtained. Applying the calculated results to the reactions catalyzed by fumarase and D-glyceraldehyde-3 phosphate dehydrogenase, we have been able to interpret experimental phenomena which could not be accounted for by the conventional theory of the diffusion-controlled reaction. Furthermore, the conditions under which the Bronsted equation is valid in the non-equilibrium steady state reaction system have been discussed.


Experimental studies on curing elapid bite with trypsin. The local injection of trypsin can be regarded as a new and effective therapy for venomous snakebite. Our experiments indicate that when mice or dogs have been injected with the lethal dose of elapid venom subcutaneously, they can all survive and have no symptoms of systemic poisoning if necessary dose of trypsin is injected locally and promptly. When the lethal dose of cobra venom is injected into mice, all of them can survive if trypsin is given within 15 minutes. And even if trypsin is given 20--50 minutes later, 50--90% of the mice can avoid death. The prompt local injection of trypsin is found effective to cure elapid bite as well as antivenins and is a very "broad spectrum' therapy having no specificity. There are no severe side-effects when trypsin is injected locally. The production of trypsin is rather simple and its preservation needs no special conditions. Trypsin can be put into pocketable first-aid auto-injector and can be used after snakebite at the possible earlier time. Even though a rather long time has elapsed after snakebite, the local injection of trypsin is still useful to destroy the large amount of venom stored in the tissues of the bitten area.


Hepatic peroxisome proliferation: induction by two novel compounds structurally unrelated to clofibrate. Two hypolipidemic compounds [ 4-chloro-6(2,3-xylidino)-2-pyrimidinyl-thio] acetic acid, and 2-chloro-5(3,5-dimethylpiperidinosufony)benzoic acid (tibric acid) greatly increased the number of peroxisomes (microbodies) in liver cells of rats and mice. This augmented peroxisome population was accompanied by significant elevation of liver catalase activity. These two hypolipidemic peroxisome proliferators are structurally different from ethyl a-p-chlorophenozyisobutyrate (clofibrate) and other hypolipidemic, arylocyisobutyrate derivatives which cause hepatic peroxisome proliferation. Induction of peroxisome proliferation by these structurally unrelated hypolipidemic compounds suggests a possible relation between hepatic peroxisome proliferation and hypolipidemia.


Alcoholic hepatomegaly: accumulation of protein in the liver. The hepatomegaly that appears after long-term feeding of ethanol results in accumulation of protein that is quantitatively as important as the increase in lipid. The bulk of protein accumulated in the soluble fraction of the cell. Hepatic albumin and transferrin concentrations increase and colchicine-binding protein decreases, thus suggesting an intrahepatic retention of export proteins.


Enemy specification in the alarm-recruitment system of an ant. Many kinds of ants use odor trails to recruit nestmates to food discoveries and new sites; minor workers of the myrmicine Pheidole dentata also use them to recruit major workers ("soldiers") to the vicinity of intruders. This newly discovered alarm-recruitment system has proved to be narrowly specific. Only fire ants and other members of the genus Solenopsis, which include some of the potentially most dangerous enemies of Pheidole, have been found to evoke the response when present as single scouts or small invading forces. The glandular source of the Pheidole trail pheromone and the cues by which Pheidole recognize Solenopsis have been experimentally determined.


Orientation of water in striated frog muscle. Proton and deuterium nuclear magnetic resonance spectra of striated frog gastrocnemius muscle exhibit angular dependence, indicating partial orientation of water in the muscle. Nonzero static dipolar and quadrupolar interactions resulting from the anisotropic motion of the water molecules modulate the spin echo decays, contributing to their nonxponential behavior.


Direction finding by hornets under gravitational and centrifugal forces. The effect of centrifugal and gravitational forces whose resultant ranged between 26 degrees and 45 degrees on comb construction by hornet workers was assessed experimentally. Comb construction by hornets exposed to centrifugation at 1 to 2 days of age differed from that of hornets similarly exposed at 3 to 7 days of age. Juvenile hornets built their cells in the direction of the resultant force, whereas adults resisted the centrifugal force and tried to build in the direction of the gravitational force. Juveniles started their comb from the side walls, whereas adults started from the roof, as did nonspinning, control hornets. The findings suggest that hornets rapidly learn the gravitational force during the first days of life, and that they are aided by geometric cues of the breeding box to build in the direction of the force to which they had become habituated.


Retention of nonhelical procollagen containing cis-hydroxyproline in rough endoplasmic reticulum. Fibroblasts freshly isolated from embryonic tendons were incubated with a proline analog, cis-4-hydroxy-L-proline, which is incorporated into protein and which leads to the intracellular accumulation of nonhelical procollagen. Evidence is presented here that the nonhelical procollagen containing the analog is retained within the rough endoplasmic reticulum and does not pass to the smooth endoplasmic reticulum or Golgi vacuoles at a normal rate.


Calcium ion distribution in cytoplasm visualised by aequorin: diffusion in cytosol restricted by energized sequestering. The distribution of Ca2+ in the cytoplasm following a local rise in Ca2+ concentration is visualized by means of aequorin luminescence and a television system with an image intensifier. Diffusion of Ca2+ through the cytosol is so constrained that a rise in cytoplasmic Ca2+ concentration produced by local Ca2+ entry through cell membrane or by local Ca2+ injection is confined to the immediate vicinity of these sites. The diffusion constraints are lifted by treatment with cyanide or ruthenium red. Thus, energized calcium sequestering, probably by mitochondria, is the dominant factor in the constraints. In cell regions where the sequestering machinery is sufficiently dense, different Ca2+ message functions inside a cell may be effectively segregated, permitting private-line intracellular communication.


Minor salivary glands as a major source of secretory immunoglobin A in the human oral cavity. Secretory immunoglobulin A is the predominant immunoglobulin in labial minor salivary gland secretions. Its mean concentration is four times higher in these secretions than in parotid gland secretion. The minor salivary glands can produce 30 to 35 percent of the immunoglobulin A that enters the oral cavity. This, together with the potential accessibility of these glands to antigenic stimulation, suggest that they may be an important source of the immune factors that are involved in the regulation of the microorganisms in the oral environment.


Vitamin B6-responsive and -unresponsive cystathioninuria: two variant molecular forms. Cystathionase activity in a lymphoid cell line extracts from a vitamin B6-responsive patient with cystathioninuria was increased strikingly by pyridoxal phosphate. Immunodiffusion with antiserum to human hepatic cystathionase showed identity between this cystathionase protein and cystathionase from an extract of normal lymphoid cells. Neither an increase in cystathionase activity nor immunochemical identity was found using extract of cells from a B6-unresponsive patient.


Cross-cultural differences in simple taste preferences. A population of Indian laborers who show high preferences for sour and bitter tastes has been studied. Their judgments of taste intensity and pleasantness of sweet and salty stimuli are in accord with European population estimates, which suggests that dietary history may alter preferences for simple taste stimuli without affecting the gustatory system.


Cochlear tuning properties: concurrent basilar membrane and single nerve fiber measurements. Removal of perilymph from the cochlea has been reported to destroy the sharp tuning of cochlear neurons. That these changes are mechanical in origin is refuted by the concurrent recording of sharp neural tuning with broad basilar membrane responses from the same region of the partially drained cat cochlea. A second cochlear filter is therefore necessary.


Sex recognition in the crayfish Procambarus clarkii. Male crayfish, Procambarus clarkii, show different behaviors toward males (aggression) and females (submission, courtship). Behavioral and neurophysiological tests with water in which the crayfish had been held demonstrated the existence of sex pheromones. The inner rami of the antennules are the site of reception, and the chemicals are probably carbohydrates.


Social class and frequency of XYY and XXY. The karyotype and paternal social class were determined for 10,348 consecutively born males. No significant difference in paternal social class was associated with the occurrence of the XYY or the XXY karyotype. This argues against the suggestion that socioeconomic factors significantly affect the frequency of the nondisjunctional events leading to these chromosome abnormalities.


Stimulation in vitro by 1,25-dihydroxy-vitamin D3 of intestinal cell calcium uptake and calcium-binding protein. Treatment of duodenal tissue from rats deficient in vitamin D with 1,25-dihydroxy-vitamin D3 [1,25-(OH)2-D3] led to more than a doubling of calcium uptake by the isolated cells and the appearacne in those cells of previously undetectable calcium-binding protein (CaBP). Treatment with the precursor, 25-hydroxy-vitamin D3, was without effect on calcium uptake or CaBP. Cells from vitamin D-replete animals took up three and a half times more calcium than cells from deficient animals. This rapid (90-minute) effect of in vitro treatment with a physiological dose (4.7 X 10(-8)M) of 1,25-(OH)2-D is the first such report and is in accord with the regulatory role of the hormone-like sterol.


Transferrin: internal homology in the amino acid sequence. Two regions of the primary structure of human serum transferrin, of 87 and 57 residues, are reported. When these are suitably aligned by placing two gaps, 40 percent of the amino acids in corresponding positions are identical. This indicates that the doubling of an ancestral structural gene occurred during the evolution of the transferrins.


Lymphocytes of the toad Xenopus laevis have the gene set for promoting tadpole development. Nuclear transplantation experiments show that differentiated cells, such as lymphocytes, from the adult frog can express the genes necessary for tadpole development. The transplanted cells were proven to be lymphocytes by immunological methods. The origin of the tadpoles that developed after lymphocyte nuclei injections was ascertained by a karyotypic marker.


Weaning and growth of artificially reared rats. The importance of suckling experience for later feeding in the rat was tested by means of an isolate rearing technique that eliminated oral feeding. Pups reared in the nearly complete absence of suckling and feeding ate and drank at weaning and then grew normally. Furthermore, the characteristics of apparently normal ingestion and growth make the artificially reared rat a useful preparation for other developmental investigations.


Locus of short-term visual storage.

Locus of short-term visual storage. A rod monochromat can preserve visual information in iconic memory even when the initial stimulus is invisible to the subject. Since the initial invisibility is due to rod saturation, it can be shown that all the information must have been stored inside the photoreceptors. Because the spectral sensitivity for producing icons in normal subjects is that of the rods, the conclusion is that in normal subjects, under ordinary viewing conditions, the photoreceptors are the primary store for iconic memory.


Spurious polycythemia.

Spurious polycythemia. Spurious polycythemia is not a primary disease process. It sometimes may be nothing more than an unusual, but normal, physiologic state. In other instances, however, it is associated with a true abnormality of plasma volume. Although there is probably overlap between these extremes, differentiation of these subclasses may be of prognostic significance. The elevation in hematocrit bears no relation to morbidity, and, because there is no evidence of abnormal erythroid proliferation, reduction of red cell volume via phlebotomy or myelosuppression is inappropriate. Nonhematologic parameters, particularly hypertension, are the major factors of significance in the substantial cardiovascular morbidity in spurious polycythemia, and they demand attentive and aggressive management.


[Use of gas chromatography--mass spectrometry in toxicology]. In the present paper, discussion has been focused upon the problem of identifying toxic substances with the aid of the GC/MS system, i.e. gas chromatography - mass spectrometry. Factors involved in a successful combination of a gas chromatography with a mass spectrophotometer have been pointed out. In addition attention has been drawn to the two various ways of obtaining the spectra, i.e. the classic EI spectra and those obtained during chemical ionization, the mode of performing mass fragmentography and, last, the importance and characteristic features of the computer-controlled GC/MS systems.


The topology of red cell membrane lipids in hereditary spherocytosis. The topology of membrane phospholipids in the red cells of patients with hereditary spherocytosis has been studied with the non-penetrating probe 2,3,5-trinitrobenzenesulphonate. There was no significant difference in the assymetric distribution of the aminophospholipids phosphatidylserine and phosphatidylethanolamine across the two halves of the membrane bilayer in red cells of five patients with hereditary spherocytosis as compared to seven normal controls. These studies indicated that the complex processes responsible for membrane lipid assymetry are intact in hereditary spherocytosis.


Identification of some substances secreted by the bovine pineal body and their antigonadotrophic activity in an in vitro system. To aid elucidation of the chemical composition of the antigonadotrophic substances produced by the epiphysis cerebri, 100 bovine pineal bodies were incubated in Krebs-Ringer buffer and the incubate treated to give an ethyl acetate and an aqueous extract. Using thin layer chromatography on fluorescent silica gel plates, 5 indoles were identified and 6 unknown substances isolated from the pineal incubate and from both extracts. The presence of peptides was detected in the incubate and in the aqueous extract. The antigonadotrophic activity of the incubate and of the two extracts was examined using a continuous flow in vitro system with the production of luteinizing hormone (LH) from bovine adenohypophysial tissue as the final parameter. All three fractions were found to result in a somewhat similar production of LH. To distinguish between the antigonadotrophic activity attributable to the indole and the indole/protein components of the pineal secretion, 90 bovine pineal bodies were homogenized and the homogenate incubated in the continuous flow in vitro system in the presence or absence of trypsin and trypsin-inhibitor. Results were inconclusive regarding the role played by the indole and indole/protein fractions in the antigonadotrophic activity of the pineal body.


The effect of inclusion of cerebrospinal fluid in the incubation medium on the in vitro secretion of luteinizing hormone from the bovine adenohypophysis. Six in vitro trials were conducted using bovine tissues to study the effects of addition of cerebrospinal fluid (C.S.F.) to the incubation medium on the secretion of luteinizing hormone (LH) from adenohypophysial tissue, both in the presence and absence of hypothalami. Additionally, a study was made of the effect of including pineal bodies on the secretion of LH in both medium alone and in medium + C.S.F. No marked or consistent effect on LH secretion was observed when the C.S.F. concentration ranged between 5 per cent and 40 per cent, when the tissues were incubated in C.S.F. alone, nor when pineal bodies were added to the culture system. These results do not support the concept that the C.S.F. contains substantial amounts of substances which enhance secretion of LH from the anterior pituitary.


Acute renal failure in Indian and Black patients. This preliminary study of 50 patients suffering from acute renal failure showed the aetiology to be medical in 30 patients, gynaecological in 9 patients, abstetric in 6 patients, and surgical in 5 patients. The commonest medical causes of acute renal failure were septicaemia and nephrotoxins (mainly from herbal medicines). The commonest gynaecological cause of acute renal failure was self-induced abortion. The relevant clinical and biochemical features are described. In spite of adequate dialysis and antibiotic therapy, the mortality was 34%. Adverse factors affecting prognosis were septicaemia, jaundice, the cause itself of the acute renal failure, and delay in beginning dialysis.


The surgery of frontal sinus infection.

The surgery of frontal sinus infection. A clinical and surgical review of 37 patients treated for acute and chronic frontal sinusitis at Groote Schuur Hospital during the 6-year period 1967-1972, is presented. The mode of clinical presentation of this disease and its complications are discussed, and the surgical management of frontal sinus disease as practised at this hospital is described.


Non-surgical management of a retained common duct stone. A case report. A case report of a retained common duct stone is presented, where a successful outcome was achieved with a solution of sodium cholate as a solvent. The non-surgical techniques of removal of retained common duct stones are discussed, and it is concluded that operative intervention is seldom necessary.


Ethrane anaesthesia for caesarean section. Fifty patients scheduled for elective Caesarean section were anaesthetised with nitrous oxide, oxygen, relaxant, and 0,5 - 1,5% Ethrane. The mothers were tilted laterally throughout the operation. Analysis of the maternal blood gas status before induction and at delivery revealed a mild respiratory alkalosis with an associated metabolic acidosis. The mean modified Apgar score (Apgar minus colour) of the infants 1 minute after delivery, was 7/8. All infants achieved the maximum score at 5 minutes. Blood gas studies on umbilical cord blood indicated a relative lack of fetal acidaemia. The results suggest that Ethrane does not cause significant perinatal depression, and that fetoplacental exchange is well maintaned during anaesthesia. The anaesthetic was well tolerated by the mothers and there were no instances of factual recall, no cardiac arrhythmias were observed, no significant hypotension was encountered and blood loss was average.


Fungus cerebri--an unusual complication of mastoidectomy. A case of fungus cerebri complicating mastoidectomy is presented and the pathogenesis is discussed.


Ulceration caused by cytotoxic drugs.

Ulceration caused by cytotoxic drugs. Five cases of severe ulceration of the dorsum of the hand and forearm, caused by the large extravasation of a cytotoxic agent, administered for haematological disorders, are presented.


Subacute combined degeneration of the spinal cord and air encephalography. Subacute combined degeneration of the spinal cord is a rare complication of vitamin B12 deficiency and is seldom encountered today. A case of Addisonian pernicious anaemia is reported in which the classical signs of subacute combined degeneration developed suddenly after air encephalography had been performed. The patient made a complete recovery.


A minimum age for measles vaccine administration to coloured children. The antibody response to further-attenuated live virus measles vaccine was assessed in 67 Coloured children between the ages of 6 and 12 months. Children less than 9 months of age were found to have suboptimal seroconversion rates and it is recommended that the routine administration of measles vaccine should be restricted to children over the age of 8 months. High-risk groups and problems of vaccine administration and storage are discussed.


The management of colon injuries.

The management of colon injuries. Surgical management of colon injuries was assessed in 97 patients. Injuries comprised stab wounds (88 cases), blunt trauma (5 cases), and gunshot wounds (4 cases). Injury involved the right colon in 52,6% and the left colon in 47,4% of patients. Fifty-eight per cent had associated major visceral injury. Patients were divided into two categories; those in whom proximal colostomy or exteriorisation of the perforation was performed constituted the one group, and those who had primary closure, the other. Analysis of results were made with regard to the incidence of wound infection, intra-abdominal abscess formation, peritonitis, and other postoperative complications. Seventeen patients had exteriorisation of the colon performed. Colostomy and colostomy closure had a significant morbidity rate, with a mean total period of hospitalisation of 58,5 days. Eighty patients were treated by primary closure. Septic complications occurred in 36,7% of cases. An analysis of the factors influencing mortality and morbidity was made, with reference to the side of the colon involved, the time interval between injury and surgery, faecal contamination of the peritoneal cavity, associated visceral injury and the presence of more than one colonic perforation. Increased morbidity was noted when the operative delay exceeded 6 hours and when faecal contamination of the peritoneal cavity was marked. Primary closure of a lacerated colon is safe provided that careful consideration is given to the above factors.


The Bernard-Soulier syndrome: hereditary giant platelet disease. A patient with the Bernard-Soulier or hereditary giant platelet syndrome, in whom the characteristic morphological features were present and the in vitro abnormalities of platelet aggregation were demonstrated, is reported. Although rare, this syndrome is important, since surgical procedures may be carried out under cover of infused allogeneic platelets.


Typhoid polymyositis.

Typhoid polymyositis. Four patients with typhoid polymyositis, 3 of whom were members of one family, are described. There was clinical, biochemical and histological evidence of severe muscle involvement which reversed on treatment with Chloromycetin. Muscle involvement in typhoid fever is a recognised pathological entity, but a clinical syndrome involving muscle has not previously been described.


Denervation treatment of affective disorders. It was assumed that affective disorders of any aetiology are systemised adrenergic neuronal denervative conditions. If so, short-term pharmacological denervation must result in completion of pre-existing partial neuronal denervation and in subsequent postdenervation supersensitivity and neuronal recovery. Clinically controlled trials in depressive syndromes of various aetiology support this hypothesis.


Trial labour conducted under continuous epidural analgesia. Two hundred Black women who required trial labour for suspected disproportion were adminstered continuous lumbar epidural analgesia by an obstetrician. The effects, side-effects, and results are described and discussed. Epidural block provides safe, effective analgesia for trial labour, and does not adversely affect the delivery or fetal condition.


Internal iliac artery ligation in obstetrics and gynaecology. Ligation of one or both internal iliac arteries is described in 5 obstetric and 5 gynaecological patients. The procedure was performed for control of severe pelvic haemorrhage. The anatomy and technique are briefly outlined, and the freedom from complications is stressed. Modern views as to the probable postoperative haemodynamics are discussed. A plea is made for more frequent use of this simple operation, and for its routine teaching during the training of pelvic surgeons.


Induction of labour with prostaglandin E2 tablets. The induction of labour with prostaglandin E2 (PGE2) tablets in two dosage regimens, and with desamino-oxy-tocin, has been studied in association with amniotomy. In multiparas at or near term and with a high Bishop score. PGE2 appears superior with regard to the induction-to-delivery interval and the duration of labour, but both preparations are highly effective in this respect. In nulliparas with a low Bishop score, however, intravenous oxytocin after amniotomy is the method of choice.


An assessment of the criteria for selection of patients for an obstetric intensive care unit. Intensive care monitoring of the fetus during labour improves perinatal conditions in 'high-risk" Black women. If the available facilities and staff are to be used with maximal efficiency, a system of priorities is necessary. It would appear that patients with meconium staining of the liquor, with cephalopelvic disproportion, or with two or more indications for monitoring, should have priority for admission to our intensive care unit. Hypertension and antepartum haemorrhage are of less importance, but there are two other problems which need investigation. There is a group of patients in labour who arrive too late to be monitored. They have a considerable perinatal mortality and the reasons for their late arrival need to be ascertained. There is a second group of patients who begin labour before term and deliver babies with a high risk of perinatal death. These problems require further investigation.


Diagnosis and treatment of advanced extra-uterine pregnancy. Eighteen cases of advanced extra-uterine pregnancy are reported. The difficulty of diagnosis is discussed; the only symptoms of any help were amenorrhoea, lower abdominal pain, postmaturity and failed induction of labour. The physical findings were variable and none were absolutely reliable. In 17 cases the fetus was dead on admission and early laparotomy was performed, and in 17 patients it was possible to remove the placenta completely.


Prolapse of the urethra in young Zulu girls. Four young Zulu girls with urethral prolapse are presented; all were under 10 years of age and all were poorly nourished. The treatment is discussed.


Serum human placental lactogen levels in intra-uterine fetal growth retardation. Serum human placental lactogen (HPL) levels were measured in the last trimester of pregnancy in 16 mothers who delivered small-for-gestational-age babies. Only 3 patients had levels which were below the normal range, while 4 others had levels close to the lower limit of the normal range. The finding of a normal serum HPL level therefore does not exclude the possibility of intra-uterine fetal growth retardation. No correlation was found between serum HPL levels at 37-39 weeks and infant or placental weights in full-term normal deliveries.


Biliary pancreatitis.

Biliary pancreatitis. Seventy-one patients with acute pancreatitis are reviewed. Biliary disease was incriminated as an aetiological factor in 17 of these patients. During the period under review, 141 patients with acute cholecystitis were treated. The age and sex incidence in these 3 groups are compared, and some diagnostic problems are discussed.


Tropical thrombophlebitis. The role of relapsing fever in its causation. In tropical thrombophlebitis the leg veins are most often involved, but in some patients thrombosis of the visceral veins may be fatal. As its cause is unknown, attention is called to outbreaks of relapsing fever in the Transvaal which effects labourers on citrus and maize farms and which often develops into thrombophlebitis. Appropriate tests for relapsing fever should be done in patients who develop this complication. Passengers on long overnight journeys by air are liable to deep vein thrombosis and should exercise to avoid it.


Maternal drug ingestion and congenital malformations. Possible interrelationships between maternal drug ingestion and infections during the first trimester and the occurrence of congenital malformations have been studied. Of 1 142 pregnancies, 3,4% ended in malformations clinically detected within 1 week of birth. For the group as a whole there was no evidence of an increased risk ratio in those mothers who ingested medicines. Possible reasons for this are discussed. Similar evaluations were carried out for pregnancies with threatened or actual miscarriages, stillbirths, and deaths occurring between birth and 1 week thereafter. The data from this limited study suggest that drugs are too often incorrectly incriminated when malformations occur. There are many other factors which can create a hostile environment for the fetus. The recommendation however, that women should avoid medicines in the first trimester, unless there are compelling reasons to the contrary, must remain.


Warfarin as a possible teratogen.

Warfarin as a possible teratogen. A case of congenital stippled epiphyses is presented, and attention is drawn to the possibility that this condition was caused by maternal ingestion of warfarin during early pregnancy.


Subacute sclerosing panencephalitis in Southern Africa. A first attempt to gather the available information on subacute sclerosing panencephalitis (SSPE) in Southern Africa has produced records of 79 cases which have occurred since 1955. An important feature of the epidemiology is the clustering of 48 cases in the 5-year period 1970-1974. Thirty of these patients were resident in the Cape Province, and most of them were from the Coloured community. An SSPE registry will be maintained at the MRC Virus Research Unit of the University of Cape Town and an appeal is made to all practitioners to contribute any relevant data on patients with this disease.


The effect of lidoflazine on ventricular ectopic activity in chronic ischaemic heart disease. The efficacy of lidoflazine was evaluated in 11 patients with chronic ischaemic heart disease. All patients had suffered one or more myocardial infarctions and all were bad risk patients with frequent ventricular ectopic beats. The patients were followed for periods of up to 23 months and 6-7 Holter tape recordings were performed at 4-weekly intervals. The frequency of ventricular ectopic beats decreased in 7 and remained unchanged in only 1 patient. One patient developed a recurrent acute myocardial infarction and 2 patients died, presumably of cardiogenic cause, but drug causation could not be excluded. It is concluded that the results justify further study of lidoflazine, not only as an anti-anginal but also as a ventricular antidysrhythmic agent.


Gas in the wound: what does it mean?

Gas in the wound: what does it mean? Gas-forming infections on the surgical service are usually due to anaerobic microorganisms such as clostridia, peptostreptococci or bacteroides, or to one of the aerobic coliforms. Factors that predispose to the development of gas infections include lower extremity vascular disease and diabetes mellitus. Early treatment based on the inital Gram-stain study as well as the clinical presentation is helpful in reducing tissue losses and increasing overall survival. Treatment for nonclostridial gas infections includes prompt adequate surgical debridement and appropriate parenteral antibiotics. When available, hyperbaric oxygen should be added to the treatment plan in all extensive clostridial infections.


Etiology of pneumatosis cystoides intestinalis. Pneumatosis cystoides intestinalis is an uncommon condition of previously unknown etiology. Experimental work is discussed which proves that either one of at least two clostridial species can produce PCI after relatively atraumatic contamination of the peritoneal cavity of germfree animals. This work strongly supports the bacterial etiology of PCI. It further suggests that vigorous and early treatment be directed toward control of the clostridial organisms in those cases where fulminating conditions associated with PCI are present.


Septic complications following gastric surgery: relationship to the endogenous gastric microflora. The microflora of the stomach is derived from both the ingestion of food and saliva and the reflux of proximal intestinal contents through the pylorus. Normally, this microflora is inhibited by gastric acid and normal gastric motility. In disease states, however, such as bleeding or obstructing duodenal ulcer, gastric ulcer or carcinoma, the level of gastric acid is reduced or the gastric motility is altered. Thus, endogenous microflora persists and often becomes the source of postoperative wound infections following gastric resection.


Management of infected vascular prostheses. Management of an infected vascular prosthesis must be aggressive. Aerobic and anaerobic cultures should be obtained immediately and broad spectrum antibiotics started at once and modified as culture and sensitivities direct. A period of intensive local wound care should be carried out for several days if possible, before removal of the infected prosthesis. Prolonged local therapy is usually ill-advised since healing is rarely permanent until the graft is removed and the patient is constantly in danger of suture line disruption. Hemorrhage requires immediate removal of the infected portion of the prosthesis. Revascularization should be considered at the time of graft excision only if limb viability is questionable; otherwise it is best to wait until the infection has cleared and the wound has healed. Immediate or late revascularization will usually require an extra-anatomic bypass through uninfected tissue. The best form of treatment is, of course, prevention, which includes meticulous surgical technique, elimination of sources of contamination prior to surgery, and the use of prophylactic, systemic and local antibiotics.


The problem of infection in total prosthetic arthroplasty of the hip. In summary, deep wound infection carries a special and disastrous significance for the patient with a total joint prosthesis. Such patients seem to be at greater than usual risk of infection, and special precautionary measures to prevent it are not only justified but imperative. These include careful preoperative preparation; special attention to rigid and exacting operative techniques for control of potential exogenous contaminants; sensible preoperative, intraoperative, and postoperative antibiotic prophylaxis for control of potential endogenous cantaminants; and continued supervision of the patient throughout the postoperative years so as to prevent potential metastatic infection from other primary sources. Pre-existing and active infections of the hip constitute contraindications to total prosthetic arthroplasty, but these rules may be suspended in certain special situations provided that the patient is willing to cooperate with the arduous and prolonged program of treatment, and fully understands the special risks involved.


The use of antibiotics in open fractures. The use of the term "prophylactic antibiotics" is probably not appropriate because we are in fact treating contaminated wounds. Only broad spectrum antibiotics that can be expected to be effective against coagulase-positive Staphylococcus aureus should be selected for antibiotic therapy in open fractures. We have found cephalothin-cephalexin therapy to be effective in significantly reducing the infection rate. However, the final selection of antibiotic treatment should be determined by the previous experience of organisms isolated and sensitivity studies done from open fracture wounds in each institution. These organisms will vary from hospital to hospital.


Pathophysiologic alterations during bacterial infusions for the study of bacteremic shock. Clearance of Pseudomonas aeruginosa from the blood stream in normal dogs was measured. An intravenous infusion of bacteria at a dose of 10(6) per milliliter per minute for two or five hours resulted in reproducible bacteremia in the 10(2) range per milliliter of blood without systemic side-effects. An identical bacterial infusion 24 hours later was characterized by enhanced clearance of bacteria and partial pyrogenic tolerance. A lethal bacterial dose of 4 X 10(7) per milliliter per minute infused for five hours exhibited an eightyfold higher bacteremia, shock and death within 24 hours. These events were characterized by leukopenia, hypothermia and hypoglycemia. Experimental results indicated that intact leukocyte bactericidal activity is the most important defense mechanism of the host in bacterial systemic infections.


Role of peritoneal absorption in ascites. The movement of water, electrolytes and protein across the peritoneum was studied experimentally and clinically in ascites. In the experimental and clinically in ascites. In the experimental studies, large amounts of solutions of various osmolar and colloid osmolar concentrations were infused rapidly into the peritoneal cavities of 32 dogs. In 26 of these dogs, the ureters were ligated before the experiment was begun; the other six dogs served as controls. The clinical studies were done in five patients with ascites. Tritium, 35S and RISA dilution techniques were used to study the kinetics of the different components of peritoneal fluid. Osmolarity changes were measured in plasma and peritoneal fluid by the freezing point depression method. Volume changes of peritoneal fluid were measured serially up to 24 hours for the assessment of the peritoneal absorption rate. The rate of fluid movement across the peritoneal membrane seems to be influenced, among others, by the composition of the intraperitoneal fluid, as well as by the properties of the membrane itself. An asymmetric pattern of peritoneal absorption rate of the different compositional elements of ascitic fluid was observed in this study which seems to interrelate with dynamic equilibrium which develops between ascites and the physiologic body fluid compartments. No cessation of peritoneal fluid absorption or a maximal reabsorption rate was observed in this study; nevertheless, variations in the rate of peritoneal absorption due to miscellaneous influences are possible.


A demonstration of microvilli on the luminal surfaces of epithelial cells of the canine extrahepatic biliary tract. Micromorphologic evidence is presented which indicates that in the dog the lining epitheliums of the intramural portion of the common bile duct and proximal part of the cystic duct are organized into convoluted folds. The mucosal lining of the extramural portion of the common bile duct appears to contain simple crypt structures. The mucosal surface of the hepatic duct is characterized by parallel ridges, longitudinally aligned with the long axis of the duct. The epithelial cells of the entire canine extrahepatic biliary tree present a topographic-dome shaped appearance, and their luminal surfaces are densely covered with microvilli.


Some immunologic characteristics of carcinoma of the colon and rectum. The leukocyte migration inhibition assay was used to asses in vitro cell mediated immunity in patients with surgically staged carcinoma of colon and rectum. Tumor cells and extracts were used in both the autologous and the homologous systems. The study was doubly controlled by the use of leukocytes from normal healthy volunteers and by autologous intestinal mucosa cells and extracts. The results revealed that the leukocytes of patients were significantly sensitized to autologous tumor cells but not to homologous tumor cells or extracts when compared with the leukocytes of normal healthy volunteers. Leukocytes of patients tested with autologous tumors or mucosa showed that only those of patients with Dukes C classification were significantly sensitized to their tumors. These results would suggest that patients with Dukes C classification were highly sensitized to their tumors and that carcinomas of the colon and rectum are heterogenous tumors.


Microaggregate formation during regional hypoperfusion. Occlusion of the infrarenal aorta in the dog is associated with formation of microaggregates. Etiologic factors involve stasis, acidosis and hypoperfusion. Upon restoration of flow, microaggregates are transported through the inferior vena cava to the pulmonary circulation as microemboli. The volume of microaggregates appearing in the inferior vena cava after restoration of flow in our experiments is small and seems inadequate to cause significant pulmonary mechanical obstruction. The vasoactivity of these microparticles, although to date unknown, may be significant in the etiology of the pulmonary alterations which were described previously.


Mechanisms of hypocalcemia in acute hemorrhagic pancreatitis. Thyrocalcitonin release mediated by glucagon secreted from the acutely inflamed pancreas has been postulated as a possible mechanism for hypocalcemia in acute pancreatitis. To test this hypothesis, hemorrhagic pancreatitis was induced in a group of thyroidectomized pigs. No source of thyrocalcitonin other than the thyroid has been described in the pig. Their subsequent serum calcium concentrations were compared with those in a group of thyroid intact pigs also given hemorrhagic pancreatitis. The results indicate that the hypocalcemia observed during the first 24 hours following induction of pancreatitis is not related to the presence of an intact thyroid. Differences observed in the degree of hypocalcemia between the two groups 30 to 48 hours after pancreatitis developed may be of significance but could be explained by dilutional differences alone. Thyrocalcitonin apparently has little if any role in the hypocalcemia observed during the course of acute pancreatitis.


Hypoglycemic effects of endotoxin in eviscerated dogs. Terminal stage, endotoxin shock in the dog is associated with profound hypoglycemia. The response of eviscerated dogs with absent pancreatic and hepatic function is compatible with insulin independent peripheral tissue catabolism of glucose, and an increased lactate-pyruvate ratio suggests anaerobic metabolism. Increased survival in dogs administered exogenous glucose indicates reversible, fuel dependent changes of peripheral tissue metabolism. Since hyperglycemia has been a predominant finding in clinical endotoxin shock, species differences are emphasized, but perhaps closer scrutiny of the terminal stages of clinical endotoxin shock would be more compatible with this experimental model. In any event, an explanation of the metabolic changes in this model may prove valuable in understanding the physiopathology of endotoxin shock.


Intraoperative bacterial transmission.

Intraoperative bacterial transmission. A clinical evaluation of bacterial penetration through operating room gowns was made during 100 general surgical procedures. A comparison of the degree of penetration through the standard cloth and a commercially available disposible gown was carried out. Cloth gowns, even in the dry state, were shown to be ineffective bacterial barriers. In addition, routine laundering of scrub suits failed to eliminate pathogenic bacteria.


Experience with extended use of Foley catheter following repair of the bladder. This study compares the results in patients who had anterior repair of the bladder managed with Foley catheter drainage for the traditional four or five postoperative days with a similar group of patients managed with continuous Foley catheter drainage far beyond the traditional period. Although the series was not large, the consistent, excellent results indicated that extended indwelling transurethral catheter technique is highly successful in avoiding common problems frequently encountered with operations upon the bladder and it is safe, effective and exceptionally simple.


The timing of biliary tract operations in patients with pancreatitis associated with gallstones. In a review of the surgical management of 64 patients with gallstone pancreatitis, recurrence of pancreatitis requiring readmission was noted in 48 per cent of those who had correction of biliary tract disease delayed to a separate admission. When patients were operated upon during the recovery phase of the first admission for pancreatitis, the hospital stay was reduced, there were no deaths and the morbidity was not increased. None of these patients had a documented recurrence of pancreatitis.


Percutaneous cannulation of the femoral artery for monitoring. This technique for the percutaneous placement of an intra-arterial cannula in the common femoral artery offers a simple method for the monitoring of blood pressure and blood gases. The morbidity of this procedure is low, and it is technically less difficult than radial artery cannulation.


Pre- and postnatal toxicity induced in guinea pigs by N-nitrosomethylurea. Oral administration of N-nitrosomethylurea at maximally tolerated doses to guinea pigs on alternate days from days 34-58 of pregnancy induced prenatal toxicity, as evidenced by a high frequency of stillbirths and intrauterine growth retardation, and postnatal toxicity, as evidenced by stunting and progressive mortality. Similar administration of N-nitrosomethylurethane at maximally tolerated doses did not induce such toxic effects.


The effects of exogenous cortisone acetate on development (especially skeletal development) and on circulating levels of corticosteroids in chick embryos. Chick embryos were treated with cortisone acetate on day 8 of incubation and the subsequent growth of the whole embryo and the development of the tibia studied to day 18 of incubation. Cortisone, at 10 ng to 2 mg/embryo decreased general body growth; above 0.5 mg/embryo it also retarded morphogenesis by as much as 3 Hamilton-Hamburger stages; and above 1 mg/embryo gross abnormalities were produced. The growth and differentiation of the tibia were affected to a greater extent than was the whole body. The reductions in tibial and total body weight were not linearly related to dose of cortisone injected. The exogenous cortisone acetate resulted in drastic alterations in the circulating levels of cortisone, cortisol, corticosterone, and progesterone, but plasma progesterone level was most readily correlated with the growth retardation. This study emphasizes that avian embryos can readily compensate for exogenous corticosteroids and that caution must be exercised when attributing causality to the substance administered.


An unusual two-tailed mouse.

An unusual two-tailed mouse. A malformation that resulted in the formation of 2 complete tails is described in a mouse that was heterozygous for the sex-linked gene Bent-tail (Bn). One of the tails appeared normal and contained 29 vertebrae, whereas the other tail consisted of 27 vertebrae and had several bends or kinks in it and also had malformed vertebrae similar to those described for the Bn gene. A comparison of the malformation with previously described bifurcated tail conditions in the mouse is presented. It is possible that this 2-tailed mouse represents a special case of X-chromosome inactivation.


Chemosis, proptosis and amaurosis in a 19-year-old male. An ectopic pinealoma was excised in 1966 and the patient received radiotherapy postoperatively. The patient developed diabeted insipidus, hypopituitarism, chemosis, proptosis, and loss of vision in the left eye. The left eye was enucleated in 1974 and a large orbital mass was found to contain malignant cells consistent with the diagnosis of germinoma. The orbital mass was in all likelihood a metastasis from the original focus of the tumor.


Cholinomimetic teratogens: studies with chicken embryos. The cholinomimetic compounds carbachol, decamethonium, neostigmine, succinylcholine, trimethylphenylammonium, and others were tested for their interference with normal chick development. All these compounds led to abnormalities of the cervical vertebrae; at higher dosage interference with normal morphogenesis involved the whole vertebral column. Hypoplasia of the leg muscles occurred with lower incidence. Responses, tested with carbachol, rose from 24 to 72 and 96 h, then declined to 120 h of incubation. Two of the cholinometic compounds used in combined treatment produced a high degree of synergism. Gallamine, benzoquinomium, butyrylcholine, and bethanechol had protective effects. Acetylcholine, at high dosage, caused defects different from the above. It is suggested that the cholinomimetic teratogens interfere with normal development by displacing acetylcholine from its receptors or by forming complexes with it.


The case of the dramatic impression.

The case of the dramatic impression. A patient has presented with mysterious vision loss following administration of eye drops for lid edema. The patient (and his attorney) blame the eye drops and the prescribing ophthalmologist. The consulting ophthalmologist describes the examination techniques and rationale that led to correct diagnosis and cure.


Effects in mice of high and low environmental temperature on the maternal and fetal toxicity of 2-sec-butyl-4,6-dinitrophenol (dinoseb) and on disposition of [14C]-dinoseb(12). Swiss-Webster female mice were treated with 2-sec-butyl-4,6-dinitrophenol (dinoseb) and maintained in an increased environmental temperature (32 degrees C) for 24 h or a decreased temperature (0-6 degrees C) for 1.5-4 h. In two experiemtns animals maintained at low temperature were kept wet during the cold exposure, to enhance the reduction in body temperature, by rinsing them with water at approximately 30 min intervals. Results from nonpregnant females indicated that increased temperature lowered the LD50 for single injections of dinoseb from 20.2 to 14.1 mg/kg and that reduced temperature for 4 h had no effect on the LD50. A 24 h exposure to 32 degrees C enhanced the effect of 3 daily dinoseb treatments of pregnant mice; it increased maternal mortality, decreased fetal body weight, and increased frequency of fetal anomalies. Fetal body weight and the frequency of malformations were the same in groups exposed to low temperature and maintained at room temperature. Disposition of [14 C] dinoseb was also determined in nonpregnant mice exposed to temperatures of 0, 24, and 32 degrees C. The periods of environmental temperature studied (3-24 h) had no effect on the rate of disappearance of dinoseb from plasma or other tissues examined.


A comparison of four projection perimeters. Instrument specifications. In addition to the original and highly popular instrument designed by Goldmann, three other projection perimeters are now available. Features of the Goldmann, Topcon, Marco and Rodenstock machines are examined and compared.


Incorporation of 5-lododeoxyuridine into the DNA of mouse embryos: its relation to embryotoxicity. Pregnant female ICR mice were administered, ip, either a trace (200 muCi/kg) or teratogenic (200 muCi + 300 mg/kg) dose of [6(-3)H] 5-iododeoxyuridine (IdU) on day 10 of gestation. Maternal liver, spleen, intestine, and kidneys, and placentas and embryos were removed at various time intervals after injection, weighed, and homogenized in cold 0.5 m perchloric acid. The half-lives of IdU-derived nucleotides in the acid-soluble fraction ranged from 31-46 min (trace) to 57-131 min (teratogenic) for the tissues analyzed. [3H]IdU was incorporated into the DNA of all mitotically active tissues after both dosages. The presence of the label in iodouracil was demonstrated by thin-layer chromatography of DNA bases extracted from maternal spleen and embryo. Growth of embryos following injection on day 10 resulted in decreased 3H-specific activity in the DNA fraction and concomitant retention of total activity. It is suggested that the previously demonstrated embryotoxicity of IdU is related to its retention at its presumed intracellular site of action.


Selection of the experimental unit in teratology studies. In teratology experiments the litter (pregnant female) rather than the fetus is advocated as being the proper experimental unit upon which to base the statistical analysis. It is pointed out that per litter tests, by being based on the average fetal response within a litter, do take the individual fetus into account. Actual experimental data are used to show that when litter effects are present a per fetus analysis is invalid and may seriously exaggerate the significance level. It is also shown that there appears to be little loss in sensitivity in performing per litter tests even in the unlikely event that there are no litter effects. Thus it certainly seems prudent to analyze teratology data with test procedures that treat the litter as the experimental unit.


The relation between maternal restraint and food deprivation, plasma corticosterone, and induction of cleft palate in the offspring of mice. The blood level of corticosterone was measured in mice following the injection on day 14 of pregnancy of a dose of corticosterone sufficient to cause a low frequency of cleft palate in the fetuses. This was compared with the blood levels present during maternal restraint and food deprivation that produced a similar frequency of cleft palate. The mean blood level over the 24 h following injection of corticosterone was 660 mug/100 ml, and during a similar period of restraint was 485 mug/100 ml. Other mice were subjected either to restraint or food deprivation for 24 h beginning day 14 of pregnancy, the plasma corticosterone levels measured during that time, and the frequency of cleft palate in late fetuses compared with the individual plasma corticosterone levels during treatment. There was a significant (P less than 0.025) correlation between high maternal corticosteroid levels and the frequency of cleft palate in the offspring of the restrained mice but not in the food-deprived animals. It is suggested that in some stressed mice endogenous plasma corticosterone can reach levels sufficient to account for the development of cleft palate.


Chromosomal abnormalities in maternal and fetal tissues of magnesium- or zinc-deficient rats. The effect of dietary deficiency during pregnancy of zinc or magnesium on maternal and fetal chromosomes was studied. Pregnant rats were given a zinc-deficient or a magnesium-deficient diet from the beginning of pregnancy and maternal bone marrow and fetal liver were removed on day 19 of gestation. Chromosome spreads were prepared and metaphases examined for abnormalities. Both magnesium- and zinc-deficient maternal bone-marrow and fetal liver cells showed significantly more chromosomal abnormalities than did those of controls. The chromosomal aberrations occurring in highest incidence in magnesium-deficient animals were terminal deletions and fragments. A higher than normal incidence of "stickiness" was also observed in cells from magnesium-deficient animals. In zinc-deficient animals, on the other hand, the chromosomal aberrations with the highest incidence were gaps and terminal deletions.


Influence of low-intensity ultrasonic irradiation on prenatal development of two inbred mouse strains. Effects of low-intensity ultrasonic irradiation on prenatal development of DHS and A/HeMk mice were studied. On day 8 of gestation (VP day = 0) pregnant females were exposed to ultrasonic waves with a frequency of 2.25 MHz and power of 40 mW/cm2 for 5 h. A low frequency of severe cranial and facial anomalies occurred that was attributable to the irradiation in both strains. The difference in frequency of malformed fetuses was marked between irradiated and untreated control A/HeMk mice, but not DHS mice. Fetal growth inhibition and death were also produced in both strains, although the possible effect of binding the pregnant mice for irradiation cannot be discounted.


Prenatal exposure to oral contraceptives and transposition of the great vessels in man. The hypothesis that female sex hormones in the first trimester of pregnancy are causally related to transposition of the great vessels (TGV) was tested by a retrospective study of 135 cases of TGV ascertained through the British Columbia Health Surveillance Registry. During 1962-1972 there was no increase in the annual incidence rates of TGV. Analysis of questionnaires completed on 58 cases revealed no definite association between inadvertent use of oral contraceptives or other sex hormones during early pregnancy and TGV.


Cellular and biochemical aspects of growth retardation in rat fetuses induced by maternal administration of selected anticancer agents. Single ip injections of 600 mg/kg 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DIC) and 900 mg/kg 5-[3,3-bis(2-chlorethyl)-1-triazeno]-imidazole-4-carboxamide (BIC) were given to pregnant Wistar rats at day 12 and the animals were killed 4 h after injection and at days 13-17 of gestation. Fetal tissues were used to determine total DNA, RNA, and protein and the data used to derive cell number and cell weight, RNA, and protein/cell. Both compounds reduced total fetal body weight, DNA, RNA, and protein but reduction of RNA by BIC was not statistically significant. These effects were observed 4 h after injection, increased with age (days 13-17), and were 3-4 times greater for DIC than BIC. By using the value of 6.2 mumug DNA/cell, cell number and per-cell values for weight, RNA, and protein, and weight: DNA, RNA:DNA, and protein:DNA ratios were computed. The per-cell values and ratios in the DIC-exposed animals were 8-44% greater and in BIC-treated animals 0-11% greater than control animals of the same gestational age. Percentage of body water was the same in the experimental and control animals. The differences in DNA, RNA, and protein are believed to be related to drug-induced growth retardation incident to total fetal DNA reduction resulting in diminished cell number.


Cholinomimetic teratogens. II. Interaction with inorganic ions. Treatment of chicken embryos after 96 h of incubation showed that the teratogenic activity of the cholinomimetic compounds carbachol, neostigmine, decamethonium, and tetramethylammonium is reduced in the presence of calcium acetate. Similarly, supplementation with potassium acetate reduced the teratogenicity of carbachol and tetramethylammonium.


Pattern of anomalies following single oral doses of ethylenethiourea to pregnant rats. Single oral administration to rats of 240 mg/kg ethylenethiourea on days 10-21 of gestation produced visceral anomalies involving the nervous, urogenital, and ocular systems, and osseous anomalies affecting the axial and appendicular skeletons. The types of anomalies and organs affected were dependent on the stage of prenatal development at the time of treatment.


Successive spontaneous abortions with diverse chromosomal aberrations in human translocation heterozygote. A patient who had 3 first-trimester spontaneous abortions (blighted ova) was found to be carrying a balanced 13/14 Robertsonian translocation. In the 2 cases cytogenetically analyzed, different chromosomal aberration were found (trisomy 16 and supernumerary D elements). Histologic examination of the placentas of all 3 abortions revealed hypovascular or avascular villi, hydropic degeneration, and occasional atypical stromal (Hofbauer-like) cells. In 2 cases the decidua was examined by light microscopy and was diffusely inflamed with a plasmolymphocytic infiltrate. The relation of the maternal translocation to the repeated abortions with chromosome anomalies is discussed.


Studies of the development of congenital anomalies in rats. III. Effects of inhibition of mitochondrial energy systems on embryonic development. Pregnant rats were treated with various inhibitors of mitochondrial oxidative energy metabolism and with lowered oxygen tension, and the embryo fetuses examined for the occurrence of congenital malformations and for changes in enzymatic activities. Treatment with all agents tested resulted in the production of skeletal anomalies. Sodium phenobarbital was the most teratogenic of the drugs tested and produced a high incidence of malformations which included cleft palate, tail anomalies, spinal retroflexion, domed head, and facial hypoplasia. Diphenylhydantoin produced a low incidence of syndactyly and oligodactyly. In addition to its effects on fetal growth and development chloramphenicol appeared to interfere with implantation. Tissue preparations from embryos exposed to sodium phenobarbital and chloramphenicol showed markedly lowered levels of DPNH oxidase activity. Cytochrome oxidase activity was also markedly lowered in the preparations from chloramphenicol-exposed embryos. Enzyme activities in preparations from embryos exposed to malonate and diphenylhydantoin appeared unaffected, although the drugs are strong inhibitors of electron transport in vitro; the lack of apparent effect may be due to the fact that both drugs do not bind to the enzyme preparations and were diluted 100- to 200-fold during preparation and assay of the tissue homogenates.


The teratogenic effects in rabbits of doxycycline, dissolved in polyvinylpyrrolidone, injected into the yolk sac. A technique was developed for injecting agents into the yolk sac of rabbits to study their teratogenic effects. On the 9th day of gestation the rabbits were laparotomized during ether-oxygen narcosis. The test substance was injected into the yolk sacs in one horn of the uterus, and as control the corresponding solvent was injected into the other horn. On the 28th day of gestation the rabbits were killed, resorptions counted, and fetuses examined for malformations. Three series of studies were made: physiological saline; polyvinylpyrrolidone; and doxycycline dissolved in polyvinylpyrrolidone (DIP). The rate of resorptions and malformations significantly increased after injection of Vibravenos. As polyvinylpyrrolidone was not teratogenic it is concluded that the teratogenic effects of DIP were probably caused by doxycycline.


The lungs in lymphangiomyomatosis and in tuberous sclerosis. Two cases of pulmonary lymphangiomyomatosis (PL) are described and 33 other cases from the literature are reviewed. These are compared with one case of tuberous sclerosis with pulmonary involvement (PTS) and 32 other cases from the literature. There are no differences in lung function between these two conditions, both of which show airways obstruction associated with diffuse radiological lung changes. There are, however, both clinical and radiological differences and also differences in the distribution of the lesions and the histological location of the excessive smooth muscle; these indicate that PL and PTS are probably different entities and not polar forms of one condition. Finally, the strictly female incidence of PL suggests a sex-linked disorder, and it is postulated that this may be related to congenital pulmonary lymphangiectases.


Physiological activity in mediastinal teratomata. The clinical details of two patients with benign mediastinal teratomata are presented. Both patients developed inflammation of the root of the neck, the first after a small dose of radiotherapy and the second after a larger dose of radiotherapy and exploration of the thoracic inlet. In both cases, exploration of the inflamed area was followed by persistent discharge of fluid which was sterile on culture. In the first case, this was found to have a high cholesterol, lipid, and amylase content. In both cases, a benign mixed teratoma, with contents including intestinal epithelium and pancreatic tissue, was removed at thoracotomy. The suggestion is made that leakage of digestive enzymes from pancreatic, intestinal or salivary tissue may be a cause of inflammation in and around teratomata, especially after surgical exploration. Early thoracotomy is advised when the condition is recognized.


Primary sarcoma of the lung.

Primary sarcoma of the lung. Primary sarcoma of lung is defined to exclude sarcomata of lymphatic origin. A series of nine patients is presented, all of whom were seen in Edinburgh. In each case there is histological proof of the diagnosis or sarcoma. From the same population and during the same period of time, 6000 cases of bronchial carcinoma presented. Eight of the nine patients underwent resection of the tumour, and the pathological findings and clinical results are described. From a review of the literature and from the Edinburgh series, a general series of 59 cases of primary sarcoma of the lung has been selected. The criteria for selection were directed at the assessment of the results of surgery in the treatment of this lesion. The five-year survival rate after 'curative' surgery is 52%, and the prognosis after surgery does not appear to depend on the radical nature of the operation.


Fascia lata valves: a clinicopathological study. Sixteen frame-mounted fascia lata valves removed from the mitral, aortic or--in one patient--pulmonary position have been detailed histologically. These valves had remained in 15 patients (11 men and four women) for periods varying between 10 and 44 months. The reason for the original transplantation was either chronic rheumatic endocarditis or calcific aortic disease. In the mitral position, the leaflet in position nearest the site of the original anterior mitral valve cusp showed the least changes. The remaining two leaflets of the fascia lata valve in the mitral position, as well as those removed from the aortic or pulmonary position, showed more severe changes; these consisted of degeneration of collagen tissue and often a severe decrease of nuclei belonging to the fibroblastic series. These changes, as well as superimposition of fibrin or fibrous tissue, tended to become more pronounced the longer the valve had remained in the patient. Viability studies in valves removed from two patients have also been undertaken showing very greatly reduced activity. The possible causes for valve dysfunction have been reviewed, and the findings in this study suggest that contraction of fibrous tissue, which sandwiches the fascia lata valve cusps, may contribute to failure of satisfactory valve function. It is concluded that fascia lata forms a poor substitute for replacement of diseased cardiac valves.


Coronary artery fistula: report of three cases. Three children are described with a right coronary artery fistula communicating with a right heart chamber. Each had a continuous murmur like that of a patent ductus arteriosus but situated at a lower level. Aortography established the diagnosis and excluded any accompanying malformation. It is concluded that to prevent complications surgical treatment should be recommended.


Oesophagomyotomy for achalasia of the cardia. Experience of 48 cases of achalasia of the cardia, treated by oesophagomyotomy, and of three cases of failed 'Heller' operation, treated by jejunal interposition, is recorded. Some technical details and the results are discussed.


Effect of atropine on sputum production. The effect of atropine on sputum production has been studied in patients with asthama, chronic bronchitis, and bronchiectasis in some of whom there was bronchorrhoea. In three patients a reduction in sputum volume was observed after atropine but it would seem that the decrease was mainly due to the inhibitory effect on salivary secretion which facilitates spitting. The one patient treated with long-term oral atropine showed a marked reduction in sputum volume although chemical constituents and viscosity levels remained unchanged, suggesting that in this case atropine had an inhibitory effect on bronchial gland secretion.


Variability of routine pulmonary function tests. Pulmonary function tests sometimes indicate a progressive deterioration and at other times a 'stepwise' worsening which may be followed by improvement. Interpretation depends on the extent of random or diurnal variations in function. Routing pulmonary function tests (VC, FEV1, FRC, and airway resistance (Raw)) were repeatedly measured in normal subjects, patients with stable irreversible airways obstruction, and patients with stable restrictive disease. In all groups there was a significant (P less than 0.001) diurnal variation in Raw, with high values in the morning, low values at noon, and rising values in the evening. The midday Raw values were about 80% of the highest daily values. The considerable random and diurnal variability seen in all tests is reflected in the range of high and low values (% of mean individual response) in individuals. The largest variation in an individual between measurements taken at two different times was 81% in Raw (range: 40% above to 41% below the mean). There was less variation in FEV1 (29%), FRC (62%), and VC (30%). Thus the finding of a stepwise change in function could reflect its natrual variability. When repeated studies are done to assess progress or the effects of therapy on disease, there are many factors, including the time of day at which the tests are performed, which should be standardized as far as possible.