Relationship between gentamicin susceptiblity criteria and therapeutic serum levels for Pseudomonas aeruginosa in mouse infection model.

In this study estimations of in vivo and in vitro gentamicin susceptibility for a series of strains of Pseudomonas aeruginosa were compared. The series included an extremely susceptible strain, typically susceptible strains by current susceptibility criteria, and strains with enzymatic and permeability-mediated resistance. In vivo testing was done by using a mice protection test involving six 1-h doses of gentamicin and an inoculum of 50 50% lethal doses of P. aeruginosa. Both normal mice and cyclophosphamide-treated mice were used. It was found that peak serum levels and serum levels of gentamicin obtained just prior to the sixth dose (fifth dose trough levels) required for protection were much higher than minimal inhibitory concentrations (MICs) or minimal bactericidal concentrations (MBCs) obtained in high-cation medium. However, first dose trough levels were similar to MICs or MBCs. Only an extremely susceptible strain, 280, could be treated at antibiotic dosages and serum levels which are considered likely to be safe in humans. A distinct inoculum effect was found in the mice tests, with a 10-fold increase in inoculum producing a 4-fold increase in the amount of gentamicin required, but no inoculum effect was found for MICs. These results suggest that current susceptibility criteria in use for gentamicin and P. aeruginosa overestimate gentamicin susceptibility, particularly when low-cation growth medium is used for susceptibility testing and when treating disseminated infection.


Unpredictable response of Pseudomonas aeruginosa to synergistic antibiotic combinations in vitro.

The combined activity of ticarcillin and each of three aminoglycosides, gentamicin, tobramycin, and amikacin, was studied with 45 clinical isolates of Pseudomonas aeruginosa. All strains individually were susceptible to each of these agents. Comparison of the results revealed highly variable interaction, both from strain to strain and from one aminoglycoside to another against the same strain. Against 11 strains, none of three antibiotic pairs tested was synergistic by conventional criteria; against the remaining 34, three, any two, or any one pair among those tested was synergistic. The minimal inhibitory concentrations of individual drugs gave no indication of the degree of synergism to be expected. We conclude that generalizations about the behavior of this organism vis-à-vis penicillin-aminoglycoside combinations in vitro are subject to many exceptions. Furthermore, no test using a particular antibiotic combination is reliable as a screen for other combinations. If this experience is duplicated in vivo, combination testing may be as important for the choice of combination therapy as individual susceptibility testing is for the choice of individual antibiotics.


Antibiotic susceptibility of clinical isolates of Listeria monocytogenes.

A broth microdilution method was used to measure the minimal inhibitory concentrations (MICs) of the antibiotics most often recommended for treatment of listeriosis. The MICs of ampicillin, penicillin, erythromycin, and tetracycline for 175 strains of Listeria monocytogenes were below the approximate MIC breakpoint for susceptible strains as recommended by the National Committee on Clinical Laboratory Standards. Inhibition diameters for 125 strains were measured by the standardized disk method (National Committee on Clinical Laboratory Standards) and compared with the appropriate MIC values. By both methods, strains were susceptible to the above four antibiotics, except for three strains, which were intermediate in susceptibility to penicillin by the disk method. Since the minimal bactericidal concentrations for ampicillin and penicillin significantly exceeded the MICs for these antibiotics, 45 strains were evaluated with ampicillin (5 mug/ml) and gentamicin (1 mug/ml) to compare the synergistic bactericidal effect of the two used in combination and singly. An increased kill of 100-fold was observed with the antibiotics combined in 19 strains after 4 to 6 h and in 40 strains after 24 h. A comparison of results with microdilution in Trypticase soy broth and agar dilution in Mueller-Hinton agar revealed that MICs for gentamicin, kanamycin, and streptomycin were strongly influenced by the media used. The MICs were consistently lower in Mueller-Hinton agar.


Characterization of a small plasmid determining resistance to erythromycin, lincomycin, and vernamycin Balpha in a strain of Streptococcus sanguis isolated from dental plaque.

A plasmid determining resistance to erythromycin (inducible), lincomycin, and vernamycin B(alpha) was isolated from a strain of Streptococcus sanguis isolated from dental plaque of a patient who had been on erythromycin therapy for an extended period of time. The plasmid, designated pAM77, had a molecular weight of 4.5 x 10(6) and was present to the extent of one to two copies per bacterial chromosome. The plasmid could transform S. sanguis strain Challis.


Controlled trial of disodium cromoglycate in prevention of relapse of steroid-responsive nephrotic syndrome of childhood.

A controlled trial of disodium cromoglycate treatment of steroid-responsive nephrotic syndrome failed to show a therapeutic effect on the tendency to relapse after withdrawal of corticosteroids.


Amoebiasis in northern Nigeria. An evaluation of the gel diffusion test.

Sera from 778 patients presenting a hospitals in Zaria and Kaduna, northern Nigeria, were tested for amoebic precipitins by the gel diffusion test; 106 (14%) were positive. Positive tests were obtained in 16 of 18 patients with an amoebic liver abscess, in 17 of 31 patients with amoebic dysentery and in three of 100 apparently healthy controls. Positive tests, and clinical cases of amoebiasis, were seen more frequently in the wet season than in the dry season.


Portal hypertension and chronic salmonellosis in situs invertus.

The unique combination of a late complication of Schistosoma mansoni infection in situs invertus is reported. The improvement in both the haematological and biochemical indices of the patient after splenectomy is discussed. An association between chronic salmonellosis and schistosomiasis is demonstrated; the experience of the author and other workers with this syndrome is discussed.


Follow-up study of epileptic patients following forel-H-tomy.

Stereotactic Forel-H-Tomy has been performed in 20 cases of epilepsy refractory to medication of which 15 have been followed from 2 to 7 years. The outcome of operation in 7 cases is judged as 'markedly effective' or 'effective'. In 3 cases the operation was ineffective. Effectiveness was greater in bilateral operation. Improvement of EEG was indicated by disappearance or marked reduction of spikes (or sharp waves) or spike and wave complex. Grand mal seizures alone or cases of minor seizure alone have responded more favorably than other clinical types. Six cases demonstrated improvement of personality and emotions.


Functional ablation by spreading depression: possible use in human stereotactic neurosurgery.

Spreading depression (SD) of EEG activity was elicited by microinjection (5 microliter) of 5% potassium chloride into the caudate nucleus (n = 7) or hippocampus (n = 3) during stereotactic brain surgery in patients with focal epilepsy. An electrode-cannula assembly for eliciting and recording the slow potential waves of SD is described. The parameters of SD in human brain are similar to those in lower mammals. Functional ablation by SD can be used as a diagnostic tool in neurosurgery.


Metabolism of sulpiride in man and rhesus monkeys.

The metabolism of 14C-carbonyl-sulpiride (form A) and of 14C-3, 4 pyrrolidine-sulpiride (form B) was studied in the rhesus monkey and man. In the monkey, the metabolites in both the urine and the bile were the same with form A and form B: 60-80% sulpiride, 10-30% 5-oxopyrrolidine sulpiride and 3-8% an unidentified metabolite (ME-X). In four human volunteers given a single oral dose of either 108 mg form A or 100 mg form B, more than 95% of the 14C recovered in the urine and feces was unchanged sulpiride. Sulpiride levels in plasma reached maximum in 3 hr and ranged from 232 to 403 ng/ml. The plasma t1/2 was 8.3 hr. Pharmacokinetic analyses indicated little or no biliary excretion of sulpiride in man.


Gamma heavy chain disease seen initially as gastric neoplasm.

A patient with abdominal pain, weight loss, and a gastric mass was found to have a pleomorphic infiltrate of lymphocytes and plasma cells. Analysis of serum proteins revealed gamma heavy chains, which were detected in the urine as well. This case is unusual because of the extralymphatic involvement and the possibly unique character of the heavy chain, an insertion in added polypeptides.


Cryoglobulinemia and amyloidosis associated with intestinal lymphoma.

A case of lymphocytic lymphoma of the small intestine was associated with cryoglobulinemia and amyloidosis. The neoplastic lymphoid cell demonstrated surface IgG membrane markers by immunofluorescence and immunoelectron microscopy. The cryoglobulins were characterized as monoclonal IgG3 proteins with lambda light chains. Amyloidosis of the small intestine and regional lymph nodes was found in association with lymphatic infiltration of these organs, suggesting the production of amyloid in situ.


Composition and potential use of some tropical fruits.

The nutritional role fruits could play in poor-quality diets, as sources of vitamin A and ascorbic acid, is described. Likewise, summarized information is presented on the use of some unknown tropical fruits relatively abundant in Central America as components of high-protein foods, providing nutrients such as provitamin A and ascorbic acid, as well as a variety of flavors. In these studies the fruit pulp as a purée was added either fresh or drum-dried, to a corn-soybean blend. In all cases there occurred a decrease in protein quality, which was more marked for some fruits than for others, probably due to the dehydration process used. The chemical composition of other tropical fruits, not consumed by people but which could be used as animal feed, is also presented. This type of fruits includes the Chalum (Inga, spp.) and some Cucurbitaceae. Others contain seeds with a high oil and protein content. Among the latter, Jícara (Crescentia alata) offers very good industrial possibilities.


An epidemiological study of pre-school child malnutrition in Santo Domingo.

This report describes the differences in social and demographic characteristics of 82 mothers with a severely malnourished child under the age of five years and those of 82 mothers with a healthy child matched by age, sex, and neighborhood of residence. The mothers of the healthy children had a mean parity of 4.7 live births. There was no significant difference in the proportion of women in the two groups currently using contraception, but more women of the control group had undergone one or more spontaneous or induced abortions. More children of the control group had been immunized against one one or more communicable diseases than the children of the case group. The proportion of children of school age attending school was greater on the part of the children in the control group than the children of the case group although the difference was not significant (p = 0.06). Despite the authors' efforts to assure that the women of the control group were selected from the same socioeconomic class as the women of the case group, there was some evidence that the women of the control group enjoyed somewhat higher family incomes.


[Descriptive study of Fortesan: a new food product for preschool children].

Pre-school Children acceptability of a high nutritive value and low cost new food product (Fortesán) was studied. This mixture is formed by W.S.B. powdered milk and cacao. The purpose was to establish its a acceptability by the children and their mothers, in the Santiago population. A similar study had been already performed in 1972 in another marginal urban area and in rural areas. Inicial and final heights and weights were measured, and a socio-economical and acceptability survey was performed in all cases. The same experimental group was used as a control of it self. The study lasted 4 months, from April-May 1973 until August-September 1973. The sample was formed by children from 1 to 6 years old, coming from different socioeconomical levels. Results showed a good acceptability of the product both by the mothers and their children. It also showed a good influence in the height and weight that the children reached.


[Nitrogen balance in adults and experimental study in rats fed with rice, beans and manioc flour supplemented with proteins].

Rice, beans and manioc flour are foods eaten daily in Northeast Brazil. Manioc flour is a source of energy, having a low protein content. There has been a great interest to supplement manioc flour with proteins. The present study was planned to show the nutritive value of a basic diet including rice, beans, manioc flour and other local foods, supplemented with different sources of proteins. The experiment was carried out in humans and rats. The supplements used were casein (Ca), isolated soy protein (PS) and a dry residue of a soymilk preparation (RSLS). Through nitrogen balance studies in adults it was shown that the diets with casein or isolated soy protein had a good absorption and retention of nitrogen. The addition of the soymilk residue resulted in a poor acceptance of the experimental diet; negative nitrogen retention was observed in the three persons who accepted the food and completed the balances studies. The same diets offered to humans, with the same protein supplements, were fed to rats. The nutritive value measured in the animals were similar, in all diets with all supplements, including the one with the dry residue of soymilk. The present results call the attention to the problems of transfering animal results to humans. It was also discussed the possibility of adding casein or isolated soy protein as an eventual protein supplement to manioc flour for human feeding.


[Cardiac amyloidosis: clinical, x-ray, electric, hemodynamic, developmental and pathological aspects. Apropos of 85 cases collected from French cardiology departments].

85 cases of cardiac amyloidosis have been collected from the university cardiac departments of France. Four distinct clinical pictures have emerged: 1. Primary cardiac amyloidosis (36 cases) which combines: congestive cardiac failure, ECG signs (extreme axis deviation, low voltage, signs of myocardial necrosis), arrhythmias (67%), and a rapidly fatal outcome (23.2 m +/- 8.5); 2. Cardiac amyloidosis associated with a marked neuromuscular amyloidosis (8 cases), in patients of Portuguese extraction (4 out of 8), with a positive family history (6 out of 8), characterised by arrhythmias (5 out of 8), and with a better prognosis (1 death out of 8); 3. Cardiac amyloidosis associated with a dysglobulinaemia (14 cases) with a clinical picture which is almost identical with that of primary cardiac amuloidosis; 4. Senile cardiac amyloidosis, whose frequency increases with age, may sometimes be discovered at routine post mortem examination, and is characterised by atrial fibrillation (13 out of 27) and its association with anaemia, signs of inflammation, and coronary atheroma.


[The cardiomyopathy of idiopathic hemochromatosis].

A retrospective study of the case histories of 216 patients with idiopathic haemochromatosis has highlighted the frequency of cardiac involvement in this condition (53%). Two forms can be distinguished: a latent one (65%), in which the changes are predominantly electrocardiographic, and a clinical form (35%) with the features of congestive cardiomyopathy, notable for the rapidity of onset after right heart failure, the degree of cardiomegaly, the constant finding of abnormalities of ventricular repolarisation, the relative frequency of latent disorders of supra-His atrio-ventricular conduction, and the finding of elongation of the isovolumic contraction time on the phonomechanocardiogram. A haemodynamic profile is the same as for non-obstructive hypotonic cardiomyopathies, and is usually associated with a slow rise in left ventricular pressure. The cardiomyopathy, which is the most frequent cause of death, determines the prognosis in this condition. It may be found in association with diabetes and gonad failure. The finding of cardiomyopathy indicates basic treatment by veresection, which may be the only means of establishing a favourable outcome.


[The myocardiopathies of systemic lupus erythematosus].

Myocardial involvement in lupus erythematosis takes the form of an interstitial myocarditis with cellular infiltration and fibrinoid necrosis. The most lesions are perivascular, and involve the arterioles. The myocardial fibres are involved secondarily to the vascular lesions, or by grossly, damaging sclerosis. The clinical features are variable:--no clinical features, but haemodynamic evidence of abnormal ventricular function, and perhaps sudden death;--arrhythmias and disorders of atrio-ventricular conduction;--cardiac failure, which may be due to a genuine cardiomyopathy (a part may be played by hypertension, pulmonary hypertension, renal failure, constrictive pericarditis or haemodynamically major valve disorders);--abnormalities of the coronary trunk in a certain number of cases. If anti-nuclear antibodies are present in a cardiomyopathy, the presence of DLE or of a drug-induced lupus syndrome must be suspected. There remain some awkward cases which defy classification, and which systematic use of echocardiography and pericardial and myocardial biopsy may be able to define more accurately.


[The sclerodermic myocardiopathies].

Sclerodermic cardiomyopathy is the commonest cardiac lesion in this collagen disorder. The picture is a common-place one of left ventricular failure with moderate cardiomegaly (unless there is an associated chronic pericardial effusion). There are no characteristic features on the ECG. The prognosis is particularly poor, with death within one or two years. Clinical presentation of the cardiomyopathy may be preceded by isolated ECG changes occuring over one or two years. The myocardial disorder, which is often associated with latent pericardial and endocardial lesions, is peculiar to scleroderma out of all the collagen disorders, but presents no difficulty in differential diagnosis because of the other features of the disease of which it is a part.


[The myocardiopathies of hereditary neuro-muscular diseases].

This joint work has studied the cardiomyopathies occurring in hereditary neuro-muscular disorders (270 cases). The Duchenne type of disorder (74 cases) was responsible for asystole (4 cases), for cardiomegaly, and especially for abnormalities of the ECG (59 cases)--Q waves and large R waves in V1 and V6. The cardiomyopathy was of the hypokinetic type, with histological evidence of degeneration of the myocardial fibres. Dystrophia myotonica of Steinart (23 cases) caused conductive disorders (17 cases) which were either atrioventricular or intra-ventricular or both. Studies of the His pathway confirmed that these abnormalities were more diffuse in 5 cases. The main histological feature was interstitial fibrosis. There was a high risk of sudden death; ECG follow-up should be close. Friedreich's disease (20 cases) in its complete form led to later development of obstructive cardiomyopathy, with a systolic ejection murmur, cardiomegaly, and abnormalities of the ECG--left ventricular hypertrophy in the vertical axis, right ventricular and septal hypertrophy, repolarisation disorders similar to those found in coronary artery disease. Histology showed hypertrophy with degeneration of the myocardial fibres and interstitial fibrosis. This complete form was rare (7 cases out of 20); on the other hand, ECG abnormalites were very common (16 cases out of 20). The authors have tried to study the relationships between primary cardiomyopathies (50 cases) and peripheral neuromuscular disorders. 17 of the 39 peripheral muscle biopsies were abnormal, but a well-defined muscular dystrophy could not be found in them.


[Myocardiopathy of pregnancy in white women].

Over the course of 17 years, 7 women have had heart disease either during the last three months of pregnancy or during the first three months post-partum, which appear to be associated with their pregnancy. Enquiries made throughout the country and relating to the last decade have yielded 11 additional cases so far unpublished. The clinical features of these cases do not differ from those of other non-obstructive cardiomyopathies occurring other than in pregnancy. The prognosis depends essentially on the factor of cardiac volume during the first few months of the disorder: if significant cardiomegaly persists, death will follow in one case out of two. There exists the problem of the criteria for making a diagnosis of myocardial disease of pregnancy. It should be emphasised that only 4 of the 18 cases were different from the usual cases of myocardial disease, in that they progressed to recovery which is unusual in this condition. One case was particularly illustrative of this, as clinical cure was followed by a relapse at subsequent pregnancy. Because the pregnancy itself seems to be the cause in such a tiny number of cases, a new hypothesis seems right; this is that pregnancy does no more than aggravate an associated or already existent myocardial disorder.


[Apparently primary acute heart failure in infants. Long-term outcome].

Cases of acute cardiac failure which are apparently primary, and occurring in babies or young children have one characteristics clinical picture. There are three etiological agents, which cannot be differentiated clinically: myocarditis, fibroelastosis, and primary non-obstructive cardiomyopathies. When the critical early period, which still carries a high mortality, has been passed, the outlook is relatively favourable. 61 babies or infants of less than 30 months with acute primary cardiac failure were followed up for a period of between 5 and 20 years. 33 of them were considered cured; 22 have minor sequelae (most frequently) left ventricular hypertrophy on X-ray or ECG); 3 have persistent cardiac failure despite treatment; 3 have died after a period of more than 5 years. There is no clinical, X-ray or ECG finding which can predict the longterm outlook in this condition. It is virtually impossible to differentiate between myocarditis and firboelastosis; it seems likely in the majority of cases that we are dealing with different modes of development in the same condition.


[Prospective etiologic survey on apparently primary nonobstructive myocardiopathies in adults. 57 cases, excluding ischemic cardiopathies].

A prospective study into the aetiology of presumed primary non-obstructive cardiomyopathy was carried out in 57 patients who had no lesions of the trunk of the coronary artery; one case of haemochromatosis and one of amyloidosis were found. Excluding these two cases of cardiomyopathy which were in fact secondary, most of the others were associated with manifestations or with complications of myocardial diseases (two pulmonary emboli and one case of jaundice) or pathology associated with it. Investigation into possible infection, biochemical abnormalities and dietary indiscretion (alcohol, colza oil), were unfruitful. Electromyographic changes of the "myositic" type were very common. The bicycle ergometry test was often interrupted through fatiguing of the peripheral muscles. These findings suggest that the muscular abnormalities may not be limited to the heart. The cost of an enquiry of this type has been investigated.


[Cardiac complications of thoracic radiotherapy].

The cardiac complications of radiotherapy have been reviewed in the light of 46 case histories collected from 16 treatment centres in France. They are usually found after radiotherapy for Hodgkin's disease and carcinoma of the breast. Although histologically there may be diffuse fibrosis involving the endocardium, myocardium and pericardium, it is pericarditis which is the usual clinical feature. It often occurs late, and takes many forms. The dry constrictive fibrous type of pericarditis is the most severe because of the amount of myocardial fibrosis usually associated with it. It is rare for there to be clinical features of myocardial fibrosis, and if present they are variable: isolated disorders of repolarisation or of conduction, or true cardiomyopathies. Lesions of the coronary arteries are exceptionally rare after radiotherapy, and involve fibrosis of the intima or atherosclerosis.


[The heart and drug poisoning, excluding cardiologic treatments].

When considered strictly from the viewpoint of actions on the myocardium, the number of drugs falling into this category is limited, but the resulting conditions may be serious. The prototype for cardiac toxicity is the group of antimitotic drugs (adriamycin or daunomycin). If these drugs are used; frequent and careful follow-up is necessary, the dosage at which the drug becomes cumulative must be known; and patients with a pre-existing cardiac condition must be exluded from treatment. Above all, it is essential not to wait until asystole occurs, but to try to prevent such occurrences by monitoring the patient electrocardiographically. A part from these drugs, recent articles in the literature suggest that similar care should be taken when prescribing emetine and lithium salts. There is insufficient information about other drugs which may have a certain degree of cardiotoxicity. For this reason, it is most important to gather information on accidents and reaction during treatment.


[Secondary coronary fistulas].

These fistulae are very rare: 8 to 11 p. 100 of all coronary fistulae. Three types are recognised: right coronaro-ventricular, left coronaro-ventricular, and coronao-pulmonary. The two first types are found most frequently in association with a sigmoid atresia on the orifice, and with ventricular hypoplasia in the presence of a functional atrio-ventricular valve. The fistula then serves as a means of ventricular ejection. Of the secondary fistulae, the right coronaro-ventricular type is the most common (73 p. 100). The authors have found 30 cases in the published literature, and add 2 of their own. They have also reviewed the clinical features and the findings on coronary arteriography and post mortem studies on such fistulae. They discuss their etiology, pathogenesis, and physiopathology. Surgical correction involves repairing the fistula in one stage. Fistulae of the left coronaro-ventricular type are exceptions to this rule (9 p. 100), as they are always associated with a rapidly fatal hypoplasia of the left side of the heart. Coronaro-pulmonary fistulae (18 p. 100) are usually found in association with extreme forms of Fallot's tetralogy, and a relatively simple surgical correction can form part of the total correction of the tetralogy.


[The exercise test in congenital aortic stenosis].

Exercise tests can be carried out without risk in a child or young adult with asymptomatic congenital aortic stenosis. In such a case, the ECG at rest gives only a very poor indication of the severity of the stenosis, which often becomes worse with age. The only sinister findings is that of repolarisation defects, which are almost always absent at rest. Exercise, by causing an imbalance between myocardial oxygen consumption and oxygen transport, will cause "ischaemic" signs to appear on the ECG. At the same time, the absence of compensation of pressure is a very important sign of poor tolerance; the test can usefully be concluded by using a floating catheter to measure the pulmonary capillary pressure. The correlation between a positive test and the stenotic pressure gradient, measured on catheterisation at rest, is good; but "negative" tests may be found in certain cases with a tight stenosis, especially if maximal rate could not be reached. In cases of stenoses which were initially mild or moderate, this test is very useful as a follow-up procedure, as such stenoses may become worse with age and require surgical correction. It is also useful for assessing the results of surgery, and of rehabilitation.


[Surgical correction of tetralogy of Fallot with an iatrogenic obstruction on 1 branch of the pulmonary artery].

The au;hors report 12 cases of Fallot' tetralogy with stenosis or obstruction of one of the two branches of the pulmonary artery following palliative anterior anastomosis. The complications of correction by open heart surgery include the frequent incidence of pulmonary hypertension, which was responsible for 4 deaths. No satisfactory explanation could be found for these poor results. It is desirable to avoid the creation of asymetry in pulmonary blood supply in Fallot's tetralogy and, if such should be found, suggestions are made for its correction by open heart surgery in order to improve the prognosis.


[Long-term results of 156 Mustard operations for simple transposition of the great vessels].

156 children with simple transposition of the great vessels have been operated on by Mustard's technique between 1-6-1967 and 31-12-1976, with an immediate overall mortality rate of 8%. In the longterm, the 9% of late deaths and more especially the complications are regrettable; complications were either of severe arrhythmia (almost 30%) leading to 2 late deaths and 7 pacemaker implantations, or venous obstruction relating to problems with the patch (25%). Despite the improved techniques and consequent reduction in surgical mortality and late complications, longterm prognosis is still unsure because of the unknown fate of the intra-atrial partition, and that of the "passive" rhythms which are so commonly found after this type of surgery.


[Echocardiography in Ebstein's anomaly. Apropos of 12 cases].

The authors report 12 cases of Ebstein's disease, and have studied the echocardiographic findings in these cases. The results have been compared with those of a control series of 12 patients with an atrial septal defect and a large shunt effect. There are only two conditions which are important in the diagnosis of Ebstein's disease: the finding of the tricuspid valve beyond the midclavicular line, and a delay in the closure of the tricuspid valve greater than or equal to 0.06 seconds when compared with the mitral valve. Using these two criteria, the diagnosis could be made by echocardiography in 10 cases out of 12.


[Results of the surgical treatment of congenital mitral insufficiency].

The authors report 21 cases of congenital mitral incompetence undergoing surgery between 1972 and 1977. There were 3 operative deaths and 2 late deaths. Of the survivors, 10 had a good result and 5 a fair result. The factors influencing the results have been associated lesions (aortic stenosis and ventricular septal defects are more serious than atrial septal defects and abnormalities of origin of the left coronary artery), the type of repair (which is better if it seeks to correct the frequently complex valvular abnormality at all levels), and especially the degree of dilatation of the left ventricle. By contrast, age had no influence either on the operative risk or on the quality of the results.


[The "small aortic ring." Hope for a surgical solution].

The "small aortic ring" was until recently an unresolved problem for surgeons operating on the aortic valves. It used to contraindicate valve replacement in the child, and sometimes led to the insertion of too small a valve in the adult. Some hope of a solution has appeared in the form of three new techniques: enlargement of the aortic ring over the mitral valve, aorto-ventriculoplasty, and apico-aortic shunt. Two adults have had the ring enlarged above the mitral valve with good results in both cases. Five children have had an aorto-ventriculoplasty with good results in two cases, post-operative atrio-ventricular block in one, and two deaths, one early and the other late. These deaths appear to be more closely related to the severity of the initial lesion and to the degree of decompensation of the myocardium than to the operation itself. There are advantages and problems with this technique. An attempt has been made to systematise indications for treatment as a function of the lesions and the state of the patient.


[Aberrant left pulmonary artery. Apropos of 5 operated cases].

The authors report 5 cases of aberrant left pulmonary artery undergoing surgery with 3 successful results and 2 failures; 4 of the 5 operations were carried out through a sternal split with either extra-corporeal circulation or circulatory arrest and profound hypothermia. The authors have reviewed the cases reported in the literature which amount to 78, 51 of which have been operated on surgically, the condition having been corrected in only 34 of them. They have studied particularly the incidence of associated tracheo-bronchial lesions which are themselves the reason for the seriousness of the condition, as well as the longterm results and the possible incidence of thrombosis in the anastomosis. By contrast with the views of Sade, the authors are optimistic about the results which have been obtained in the survivors.


Heterocomplexes of human interferon and immunoglobulins: formation and properties.

To form heterocomplexes, human diploid fibroblast interferon was reacted with an excess of human immunoglobulin in the presence of an optimal concentration of glutaraldehyde. There was virtually no loss of interferon activity due to this treatment and the resulting heterocomplexes possessed the biological properties of both native interferon and immunoglobulin molecules. The apparent molecular weights determined by gel electrophoresis in the presence of sodium dodecyl sulfate were 20,000 for native interferon and 0.5 to 1 X 10(6) for the heterocomplex. Native interferon injected into mice intramuscularly had a serum half life of about 5 hours. However, serum interferon was not detected in mice receiving a similar dose of the heterocomplex.


Efficacy of penicillin G, cefazolin, and gentamicin in M-K medium at 4 degrees C.

Corneal-scleral shells are routinely stored in McCarey-Kaufman (M-K) medium at 4 degrees C. Antibiotics are added to the medium to suppress bacterial growth. We examined the antibacterial activity of penicillin G potassium, 100 microgram/ml, cefazolin sodium, 100 microgram/ml, and gentamicin sulfate, 20 microgram/ml against test organisms in M-K medium at 4 degrees, 23 degrees, and 37 degrees C for periods up to 18 hours. Within the limits of the experimental conditions, none of the antibiotics used could be relied on to sterilize an inoculum of sensitive bacteria in M-K medium at 4 degrees C, the recommended storage temperature.


Laboratory studies on the transmission of yellow fever virus by Aedes (Finlaya) notoscriptus (Dipt., Culicidae).

Aedes (Finlaya) notoscriptus (Skuse), a mosquito which occupies a similar ecological niche to Aedes (Stegomyia) aegypti (L), the urban vector of yellow fever virus, was screened as a possible vector of this disease. The results indicate that almost certainly Ae. notoscriptus is refractory to the virus and could not act as a vector if yellow fever were introduced to Australia.


Chemotherapy for malignant melanoma: a brief review and personal experience.

Chemotherapy for melanoma can be divided into four types: (i) intralesional chemotherapy; (ii) systemic chemotherapy to prevent the development of anticipated metastases; (iii) therapy for established disease; and (iv) combined with immunotherapy. Apart from a few general rules, it is difficult to predict the response to treatment. The smaller the bulk of tumour, the more likely is regression under treatment. Metastases in the skin, and to a lesser extent those in lymph nodes and lung, respond better than those in the liver and brain. Any response in established disease is likely to be temporary, although the patient tends to develop fatal disease at sites different from those involved when he or she was first treated. The best agent at present is imidazole carboxamide (D.T.I.C.), and its effect is not enhanced by combining it with other drugs. Combined prophylactic chemotherapy and immunotherapy is still under investigation, but the results are encouraging.


Limb salvage using preoperative intraarterial adriamycin and radiation therapy for extremity soft tissue sarcomas.

Surgical therapy has been the accepted method for management of most soft tissue sarcomas of the extremities, although it has been associated frequently with local treatment failure. Even when local control was achieved, over 50% of the patients with soft tissue sarcomas eventually developed and succumbed to distant metastases of their disease. Therefore, single modality therapy for soft tissue sarcomas by operation alone results in an unacceptably high incidence of treatment failure. Fortunately, new adjuvant treatment techniques have been developed that seem to have activity against these neoplasms. It is the purpose of this article to discuss our experience with a number of these techniques.


The tourniquet.

The morbidity of the tourniquet is not well documented. The "post-tourniquet syndrome" is the most common side effect, but is usually unrecognized. The causation of nerve palsy, although this sequela is uncommon, has been documented. Other problems associated with tourniquet use are discussed.


Comparison of bacterial cardiotoxins: thermostable direct hemolysin from Vibrio parahaemolyticus, streptolysin O and hemolysin from Listeria monocytogenes.

Some properties of the bacterial cardiotoxins, thermostable direct hemolysin from Vibrio parahaemolyticus (vibriolysin), and streptolysin O and hemolysin from Listeria monocytogenes (listeriolysin), were compared. These toxins had rapid lethal effects on mice when injected intravenously. The electrocardiographic changes of rats after intravenous injections of these toxins were very similar, showing bradycardia and inhibition of atrio-ventricular conduction. These toxins also caused cessation of the spontaneous beating and degeneration of cultured foetal mouse heart cells. When equal hemolytic units of these three toxins were administered, vibriolysin had the most potent effects on mice and cultured mouse heart cells. Differences in the kinetics of the hemolysis by each toxin and in the effects of cholesterol of their hemolytic actions suggest that the mode of action of vibriolysin is different from those of streptolysin O and listeriolysin.


Separation of oestrone UDP-glucuronyltransferase and p-nitrophenol UDP-glucuronyltransferase activities.

Rabbit liver UDP-glucuronyltransferase activity was resolved into two separate fractions on DEAE-cellulose, one containing most of the transferase activity toward oestrone and the other most of the activity toward p-nitrophenol. These two activities were completely separated by rechromatography of each fraction on a second DEAE-cellulose column.


Phospholipid content and activity of pure uridine diphosphate-glucuronyltransferase from rat liver.

Rat liver phospholipids were radioactively labeled in vivo before purification of UDP-glucuronyltransferase to homogeneity. The pure enzyme contained very little phospholipid (approx. 0.7 mol of phospholipid/mol of protein). The solubilization detergent Lubrol 12A9 appeared to act as a phospholipid substitute, capable of supporting UDP-glucuronyltransferase activity. Phospholipase C did not inhibit the pure enzyme activity and pure UDP-glucuronyltransferase was stimulated by 40--100% by the addition of phospholipid dispersions.


Chrysotherapy in psoriatic arthritis. Efficacy and toxicity compared to rheumatoid arthritis.

Chrysotherapy was given to 14 patients with refractory psoriatic polyarthritis and to a comparable group of 42 patients with rheumatoid arthritis. The psoriatic patients had a higher rate of remission on gold and less severe toxicity than the rheumatoid arthritis patients. Psoriatic skin lesions were not affected by chrysotherapy.


Genetics of complement deficiencies associated with lupus-like syndromes.

There appears to be an association between deficiencies of a number of complement components, particularly of the second component (C2), and rheumatic diseases, especially lupus. The meaning of this association is not clear, but the linkage of deficiency of C2 with HLA, especially HLA-A10, B18, Dw2, as well as with BfS, suggests a possible linkage to immune response genes.


Diet-induced atherosclerosis and experimental hypertension in stumptail macaques (Macaca arctoides). Effects of antihypertensive drugs and a non-atherogenic diet in the evolution of lesions.

This study was carried out to determine the evolution of atherosclerotic lesions during a therapeutic period during which regression might be appreciated. We produced aortic and coronary atherosclerosis in 27 young adult stumptail macaques (Macaca arctoides) by feeding a diet supplemented with 2% cholesterol and 25% fat. Hypertension was produced by bilateral or unilateral narrowing of the renal artery. After six months of this regimen, four monkeys were killed (group 1) and 23 monkeys were divided into three groups: group 2 received unsupplemented diet; group 3 received the same diet as group 2 and drug treatment for hypertension; group 4 was continued on the atherogenic diet and received antihypertensive drug treatment. The results indicate that deleting the atherogenic diet leads to a decrease in the lipid content of the lesions and a transformation of the lipid laden atherosclerotic plaques into lipid-poor, fibro-collagenous lesions, with a decrease in the amount of coronary luminal narrowing. Partial control of systolic hypertension by antihypertensive drugs did not accelerate the involution of the atherosclerotic lesions over the relatively short period of this study. No statistically significant correlation by regression analysis was observed between the level of blood pressure elevation, the plasma renin activity, or the degree of the drug response, and the severity and extent of the atherosclerotic lesions. Furthermore, severe arterial hypertension without an atherogenic diet (group 5) produced arteriosclerosis of the aorta, and intensified branch cushions in the coronary arteries, without inducing lipid deposition in either vascular bed.


Prostaglandin E2 biosynthesis and effect in pigeon aorta. Possible role in atherogenesis.

This study for the first time examines the biosynthesis and effect of prostaglandin E2 (PGE2) in aorta during genetic atherosclerosis. Biosynthesis of PGE2 from [1-14C]arachidonic acid was investigated in the aorta of spontaneously atherosclerosis-susceptible White Carneau pigeons and was compared with that of the atherosclerosis-resistant Show Racer breed. Most of the PGE2 synthetase activity was located in the microsomes. The synthesis was linear up to an hour and was optimal at pH 7.4. The formation of PGE2 in the aorta in the White Carneau pigeons was significantly higher (P less than 0.01) than that in age-matched Show Racer pigeons. In vitro PGE2 strongly inhibited the cholesteryl ester hydrolase activity (51.6% inhibition at 4 X 10(-7) M concentration) in the supernatant fraction of the aorta. On the basis of (1) the increased formation of PGE2 in the aorta of atherosclerosis-susceptible pigeons and (2) its effect on specific enzymes that control cholesteryl ester concentration in aorta, it is hypothesized that PGE2 synthesized at a higher rate in damaged aorta has a significant role in cholesteryl ester accumulation during atherogenesis.


Behaviour of solute and particle markers in the stomach of sheep given a concentrate diet.

1. Fistulated sheep given a concentrate diet were used to study the behaviour of solute ([51Cr]EDTA) and particle ([103Ru]phenanthroline) markers in the stomach under conditions of continuous feeding. 2. An injection of a mixed dose of [51Cr]EDTA and [103Ru]phenanthroline was given into the rumen and the time course of marker concentrations in the rumen and the abomasum was recorded. The curves were analysed on the assumption that the stomach of the sheep could be represented as two mixing compartments (reticulo-rumen and abomasum) and a time delay (omasum). This model provided a very good description of the data. 3. [103Ru]phenanthroline associated with small particles was retained in the rumen much longer than [Cr]EDTA. Although exchange of [103Ru]phenanthroline occurred between large and small particle fractions, the results suggested that small particles may have been retained somewhat longer in the rumen than solutes. However, it was clear from the results that the mean retention times for particulate matter in the rumen could not be simply obtained using adsorbable markers. 4. Cyclical fluctuations in the concentration of [51Cr]EDTA in the rumen indicated that there were daily variations in net water flux in the rumen. 5. The presence of protozoa was associated with much shorter retention times of both solutes and particles in the rumen. Protozoa were also associated with reduced rumen volumes.


2-Aminoethylphosphonic acid as an indicator of Tetrahymena pyriformis W growth in protein-quality evaluation assay.

1. The concentration of 2-aminoethylphosphonic acid (AEP) in 96 h cultures of Tetrahymena pyriformis W was studied in order to apply it as an indicator in the assay of the relative nutritive value (RNV; protozoa population with test protein:protozoa population with whole-egg powder) of protein. Foodstuffs and food mixtures of different protein contents and qualities were used as test samples. 2. RNV values based on AEP determination (RNVAEP) were compared with corresponding values calculated from protozoa counts (RNVpc), as well as with biological value (BV) and net protein utilization (NPU) of the same proteins assayed on rats. 3. Both for foodstuffs and food mixtures highly significant correlations were found between RNVAEP and RNVpc, RNVAEP and both BV and NPU, and RNVpc and both BV and NPU. 4. AEP content in the protozoal suspension was preferred to cell count as a measure of growth response, since it took into account large differences in cell dimensions that were observed between cultures grown with different test proteins.


Sugar binding properties of various metal ion induced conformations in concanavalin A.

Concanavalin A is known to undergo a first-order conformational transition when metals are added to the demetallized protein at pH 5.6 (Brown, R.D., III, et al. (1977) Biochemistry 16, 3883--3896). The rate constants for this process, which wer have measured using a polarographic technique, are identical when zinc, cobalt, or manganese occupies S1 and calcium occupies S2. The reducible sugar, p-nitrophenyl alpha-D-mannopyranoside, binds only to the locked conformational structure which is formed upon the addition of metals. The affinity of the protein for sugars is dependent upon occupancy of S1 and S2 and quite sensitive to the identity of the metal in S2. The metals may be removed from the locked protein structure and the protein temporarily retains its ability to bind with sugars but with a considerably lower affinity. The locked form of concanavalin A is unstable at a pH near 2 and unfolds to the unlocked structure with a half-life of 25 min resulting in simultaneous loss of metal and sugar binding.


Differential effects of prostaglandin synthetase stimulators on inhibition of cyclooxygenase.

The different effects of prostaglandin synthetase stimulators on inhibition of the cyclooxygenase by structurally distinct classes of nonsteroidal antiinflammatory agents suggest that the enzyme is altered by interaction with these stimulators. Reversible stimulation of prostaglandin synthetase activity by phenols and some other compounds and the relative influence of these stimulators on inhibitors of the cyclooxygenase were determined quantitatively. Two distinct classes of inhibitors were established. The fenamates were relatively weak inhibitors alone but were much more potent in the presence of phenolic compounds. In contrast, ibuprofen, indomethacin, and flurbiprofen were more potent than the fenamates and were reduced in effectiveness by the stimulators, as expected on the basis of two opposing actions. The relative potency of the cyclooxygenase stimulators (phenol greater than norepinephrine greater than tryptophan greater than benzoquinone greater than anisole) paralleled their synergistic action on the fenamates and their antagonist action on the nonfenamates. This correlation suggests that an enzyme alteration which leads to cyclooxygenase stimulation may also result in increased sensitivity to fenamates and decreased sensitivity to the other inhibitors, possibly by altering their capacity to bind.


Bacteriochlorophyll fluorescence of purple bacteria at low redox potentials. The relationship between reaction center triplet yield and the emission yield.

This work describes fluorescence yield measurements in suspensions of strains of Rhodospirillum rubrum and Rhodopseudomonas sphaeroides in which the iron . quinone complex (X) was chemically reduced (state [PIX-]; P is the reaction center bacteriochlorophyll dimer, I is the long wavelength bacteriopheophytin), and compares these with the fluorescence observed when all the traps are open (state [PIX]) and with the fluorescence observed when all the traps are closed (state [P+IX]). At 77 K the amplitude and the shape of the fluorescence emission spectrum in [PIX-] are identical to those observed in [PIX]. This is a strong indication that all the extra fluorescence observed at room temperature in [PIX-] is, in fact, caused by an efficient back reaction [P+I-X-] leads to [P*IX-]. Using an equation similar to the original Vredenberg-Duysens relationship (Vredenburg, W.J. and Duysens, L.N.M. (1963) Nature 197, 355-357) but now assuming that a single reaction center has a probability pt of trapping an excitation and (1--pt) of re-emitting it to the surroundings, we are able to calculate pt as a function of the temperature by measuring the fluorescence in [PIX], [PIX-] and [P+IX] as a function of the temperature. The calculated pt values agree reasonably well with triplet yields measured in isolated reaction centers. Finally, we have measured the reaction center triplet yield (PTR) in intact systems and we have shown that the sum of the triplet yield and the remaining loss processes (PL) in the antenna bacteriochlorophyll including the bacteriochlorophyll dimer (such as fluorescence, internal conversion or direct triplet formation) is approximately constant; if we assume that at 77 K the only process which occurs in the reaction center is the formation of a reaction center triplet, than PTR + PL=1. The energy barrier between [P*IX-] and [P+I-X-] was estimated to be 0.11--0.15 eV for a set of preparations.


Analyses of absorption and fluorescence spectra of water-soluble chlorophyll proteins, pigment system II particles and chlorophyll a in diethylether solution by the curve-fitting method.

Absorption and fluorescence spectra in the red region of water-soluble chlorophyll proteins, Lepidium CP661, CP663 and Brassica CP673, pigment System II particles of spinach chloroplasts and chlorophyll a in diethylether solution at 25 degrees C were analyzed by the curve-fitting method (French, C.S., Brown, J.S. and Lawrence, M.C. (1972) Plant Physiol 49, 421--429). It was found that each of the chlorophyll forms of the chlorophyll proteins and the pigment System II particles had a corresponding fluorescence band with the Stokes shift ranging from 0.6 to 4.0 nm. The  absorption spectrum of chlorophyll a in diethylether solution was analyzed to one major band with a peak at 660.5 nm and some minor bands, while the fluorescence spectrum was analyzed to one major band with a peak at 664.9 nm and some minor bands. A mirror image was clearly demonstrated between the resolved spectra of absorption and fluorescence. The absorption spectrum of Lepidium CP661 was composed of a chlorophyll b form with a peak at 652.8 nm and two chlorophyll a forms with peaks at 662.6 and 671.9 nm. The fluorescence spectrum was analyzed to five component bands. Three of them with peaks at 654.8, 664.6 and 674.6 nm were attributed to emissions of the three chlorophyll forms with the Stokes shift of 2.0--2.7 nm. The absorption spectrum of Brassica CP673 had a chlorophyll b form with a peak at 653.7 nm and four chlorophyll a forms with peaks at 662.7, 671.3, 676.9 and 684.2 nm. The fluorescence spectrum was resolved into seven component bands. Four of them with peaks at 666.7, 673.1, 677.5 and 686.2 nm corresponded to the four chlorophyll a forms with the Stokes shift of 0.6--4.0 nm. The absorption spectrum of the pigment System II particles had a chlorophyll b form with a peak at 652.4 nm and three chlorophyll a forms with peaks at 662.9, 672.1 and 681.6 nm. The fluorescence spectrum was analyzed to four major component bands with peaks at 674.1, 682.8, 692.0 and 706.7 nm and some minor bands. The former two bands corresponded to the chlorophyll a forms with peaks at 672.1 and 681.6 nm with the Stokes shift of 2.0 and 1.2 nm, respectively. Absorption spectra at 25 degrees C and at --196 degrees C of the water-soluble chlorophyll proteins were compared by the curve-fitting methods. The component bands at --196 degrees C were blue-shifted by 0.8--4.1 nm and narrower in half widths as compared to those at 25 degrees C.


Flash-induced changes in the in vivo bacteriochlorophyll fluorescence yield at low temperatures and low redox potentials in carotenoid-containing strains of photosynthetic bacteria.

The changes in the in vivo bacteriochlorophyll fluorescence induced by a Xenon flash at low temperatures (77--200 K) with the "primary" acceptor X chemically prereduced have been examined in whole cells of several species of photosynthetic bacteria which contain carotenoids absorbing in the visible part of the absorption spectrum. Two groups of species with different behaviour could be distinguished. In both cases a flash-induced rise of the fluorescence yield was observed with X prereduced at 77 k; as the temperature was increased the ratio of the maximum fluorescence (FM) and the basal fluorescence (F0) decreased and the kinetics of the decay of the high fluorescent state, as observed during the tail of the flash, apparently accelerated. Of the species examined the flash-induced changes in fluorescence-yield kinetics appeared to occur at higher temperatures in the members of one group (Chromatium vinosum, Rhodopseudomonas gelatinosa and Rhodopseudomonas palustris) than in the members of the other (Rhodopseudomonas palustris) than in the members of the other (Rhodopseudomonas sphaeroides and Rhodospirillum rubrum). These effects are interpreted in terms of the light-induced generation of triplet states within the reaction centre. It is suggested that the species-dependent differences may reflect differences in the molecular organisation of the reaction centre. It was found that in all species the reaction centre carotenoid triplet does not act as a fluorescence quencher under these conditions.


Phycobiliprotein synthesis in protoplasts of the unicellular cyanophyte, Anacystis nidulans.

Stable and metabolically active protoplasts were prepared from the unicellular cyanophyte, Anacystis nidulans, by enzymatic digestion of the cell wall with 0.1% lysozyme. The yield of protoplasts from intact algal cells was approx. 50%. Incorporation of L-[U-14C]leucine into cold trichloroacetic acid-insoluble material from protoplasts preparations was linear for 1.5 h and continued for an additional 2.5 h. Incorporation of radiolabeled leucine into hot trichloroacetic acid-insoluble material from protoplast preparations demonstrated protein synthesis in protoplasts in vitro. Phycocyanin is the principal phycobiliprotein and allophycocyanin is a minor phycobiliprotein in A. nidulans cells. The light-absorbing chromophore of both of these phycobiliproteins is the linear tetrapyrrole (bile pigment), phycocyanobilin. Radiolabeled phycocyanin and allophycocyanin were isolated from protoplast preparations which had been incubated with L-[U-14]leucine or delta-amino[4-14C] levulinic acid (a precursor of phycocyanobilin). The radio-labeled phycobiliproteins were purified by ammonium sulfate fractionation and ion-exchange chromatography on brushite columns. The specific radioactivity of phycocyanin and allophycocyanin in brushite column eluates (protoplasts incubated with radiolabeled leucine) was 106 000 and 82 000 dpm/mg, respectively. The specific radioactivity of phycocyanin and allophycocyanin in brushite column eluates (protoplasts incubated with radiolabeled delta-aminolevulinic acid) was 33 000 and 38 000 dpm/mg, respectively. Phycobiliproteins from protoplasts incubated with radiolabeled leucine were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. 25% of the incorporated radioactivity in protoplast lysates and approx. 60% of the incorporated radioactivity in protoplast lysates and approx. 60% of the incorporated ratioactivity in phycocyanin and allophycocyanin (in brushite column eluates) comigrated with the subunits of these phycobiliproteins on sodium dodecyl sulfate-polyacrylamide gels. Chromic acid degradation of phycobiliproteins from protoplast preparations incubated with delta-amino[4-14C] levulinic acid yielded radiolabeled imides which were derived from the phycocyanobilin chromophore. Imides from radiolabeled phycobiliproteins isolated from protoplast preparations incubated with L-[U-14C]leucine did not contain radioactivity. These results show that both the apoprotein and tetrapyrrolic moieties of phycocyanin and allophycocyanin were synthesized in A. nidulans protoplasts in vitro.


Studies on the negative circular dichroic bands around 297 nm of ribosomes from bacterial cells.

The small negative CD bands around 297 nm of isolated 30-S and 50-S ribosomal subunits were precisely measured for three bacteria, Bacillus stearothermophilus, Bacillus subtilis and Escherichia coli Q 13. The intensities of the negative CD bands of 30-S subunits were always much greater than those of 50-S subunits irrespective of the bacterial strains, which may be related to the difference in comformations of rRNAs and proteins in the complexes between these subribosomal particles. The dissociation of 70-S ribosomes into two subunits by lowering Mg2+ concentration caused evident enhancement of intensity of the 297 nm CD band, which was completely reversed by the association of the two subunits into 70-S particles. The melting profiles of CD spectra 3 B. stearothermophilus and E. coli were compared and both subunits of the former were found to be more heat stable than those of the latter. It was found that 5 M urea and 0.5% sodium dodecyl sulfate (SDS) treatment caused considerable reduction of the negative CD intensity around 297 nm of 30-S subunits but no significant change of 50-S subunits, while no significant change was observed for the CD spectra of isolated 16-S and 23-S rRNAs by the same treatment. Effects of EDTA treatment and then addition of Mg2+  on the CD spectra and fluorescence emission spectra of the subunits were also observed and the contribution by the interaction between rRNA s and proteins in ribosomes to the small negative band around 297 nm was discussed.


The purification, properties and characterization of three forms of alpha-L-fucosidase from monkey brain.

alpha-L-Fucosidase (alpha-L-fucoside fucohydrolase, EC 3.2.1.51) has been purified to apparent homogeneity (about 22 000-fold over the crude homogenate) from monkey brain. Values of kinetic constants for the purified enzyme were as follows: pH optimum, 5.0; Km, 0.22 mM; V, 913 mumol/mg per h. alpha-L-Fucose was a competitive inhibitor (Ki, 0.275 mM) of the enzyme. Evidence for the involvement of sulphydryl group(s) and carboxyl group containing amino acid(s) in the catalytic process is presented. The purified enzyme was a tetramer of molecular weight of 285 000 of identical subunits of 73 500 held together by non-covalent forces. Gel filtration studies revealed the presence of three molecular forms of the activity in the purified preparation which appeared to be the tetramer, dimer and monomer. The existence of three types of activities was also aupported by a triphasic heat inactivation profile of the enzyme at 50 or 55 degrees C and the distinctly different pH activity profiles of the differentially heat-inactivated enzymes. Immunodiffusion studies using antibody developed against purified monkey brain alpha-L-fucosidase showed that the monkey brain enzyme had only partial immunological identity with the enzymes from the non-neural tissues of monkey as well as the human and rat liver and the rat brain. However, the monkey brain and liver enzymes appeared to be similar to the human brain and liver enzymes, respectively.


Steady-state kinetics of the anaerobic reaction of soybean lipoxygenase-1 with linoleic acid and 13-L-hydroperoxylinoleic acid.

The steady-state kinetics of the anaerobic reaction of soybean lipoxygenase-1 with linoleic acid and 13-L-hydroperoxylinoleic acid were studied. Initial rates of the formation of oxodienoic acids**, absorbing at 285 nm, were measured at pH 10. About 50% of the consumed 13-L-hydroperoxylinoleic acid was converted into oxodienoic acids regardless of the initial ratio of the two substrates. A linear inhibition by both linoleic acid and 13-L-hydroperoxylinoleic acid was observed in the concentration range studied, which is on the upper side limited by the concentrations at which micelle- or acid-soap formation starts. A kinetic scheme is proposed based on one active site in lipoxygenase-1 which alternately binds the two substrates. Values for the kinetic constants were calculated by fitting simultaneously the complete set of data to the appropriate rate equation.


Solubilization and partial purification of prostaglandin endoperoxide synthetase of rabbit kidney medulla.

The microsomes of rabbit kidney medulla converted arachidonic acid into prostaglandin E2 in the presence of hemoglobin, tryptophan and glutathione as activators. When themicrosomal suspension was treated with 1% Tween 20, a solubilized enzyme was obtained which catalyzed the conversion of arachidonic acid to prostaglandins G2 and H2. The solubilized enzyme was adsorbed to and then eluted from an omega-aminooctyl Sepharose 4B column, resulting in about 10-fold purification over the microsomes. The partially purified enzyme produced predominantly prostaglandin G2 in the presence of hemoglobin, while prostaglandin H2 was produced in the presence of both hemoglobin and tryptophan. The stimulation of prostaglandin endoperoxide formation was also observed with other heme and aromatic compounds. Prostaglandin H2 synthesis was inhibited by a variety of compounds including non-steroidal anti-inflammatory drugs, thiol compounds and prostaglandin analogues with a thiol group(s).


Circadian rhythm of cholesterol-7alpha-hydroxylase and cortisol in the African green monkey (Cercopithecus aethiops).

Cholesterol-7alpha-hydroxylase in African green monkey liver had an apparent Km of 1.65-10(-4) M cholesterol and a pH optimum of 7.4. The amplitudes of the circadian maxima of enzyme activity and serum cortisol levels were significantly greater in vervets than in grivets. Fluctuations in enzyme activity and cortisol levels during the circadian cycle were positively correlated (r = 0.89). Enzyme activities and hormone levels were 2.7-fold lower over a 24-h period in the grivet than in the vervet. Cholesterol feeding reduced the enzyme activity by 40% and serum cortisol was reduced to 38% of control levels at the diurnal peak. Serum glucocorticoids may be important physiological regulators of cholesterol-7alpha-hydroxylase in non-human primates. The concentration of cortisol and its time of release appear to be factors in the hyperresponsive trait of grivets. Genetic differences between vervet and grivet races may account for differences in the amplitude and timing of the circadian rhythm of cholesterol-7alpha-hydroxylase activity possibly influenced by cortisol.


Flurbiprofen: highly potent inhibitor of prostaglandin synthesis.

Flurbiprofen, 2-(2-fluoro-4-biphenylyl)propionic acid, inhibited the formation of prostaglandin E2 from arachidonic acid by bovine seminal vesicular microsomes. It was found that flurbiprofen was an approx. 12.5-fold better inhibitor than indomethacin by comparison of their I50 values. It was suggested that the inhibition of prostaglandin synthesis by flurbiprofen might be due to the inhibition of the endoperoxygenase which catalyzed conversion of arachidonic acid to cyclic endoperoxide. Other carboxylic acid compounds such as aspirin, ibuprofen and indomethacin showed the same type of inhibition as flurbiprofen. In contrast, phenylbutazone which was a pyrozolone derivative inhibited the formation of prostaglandin E2, but not affected the endoperoxygenase reaction. The kinetic studies for inhibition of prostaglandin E2 synthetase indicated that flurbiprofen competitively inhibited prostaglandin E2 synthesis, just like indomethacin. The Ki values were estimated to be 0.128 micron for flurbiprofen and 3.18 micron for indomethacin.


Phospholipid metabolism of monkey smooth muscle cells grown in hyperlipemic serum.

The phospholipid content and synthesis of monkey smooth muscle cells grown in tissue culture with normal or hyperlipemic monkey serum were examined. The pattern of incorporation of radioactively labeled inorganic phosphate into the phospholipids of these cells was measured using a 4 h pulse of 32P. Phosphatidylcholine and phosphatidylinositol were the predominant phospholipids labeled. Although phosphatidylcholine constituted 45% of the cellular phospholipid, phosphatidylinositol had the highest specific activity. Exposure of the smooth muscle cells to hyperlipemic monkey serum did not alter the phospholipid content, composition or synthesis of these cells. The total phospholipid content of the smooth muscle cells was independent of the concentration of lipid in the media. The distribution of 32P into the phospholipids of monkey alveolar macrophages, L-cell mouse fibroblasts, and segments of the intima-media from monkey aortas is reported.


The oxidation of methionine and its effect of the properties of cardiotoxin VII1 from Naja melanoleuca venom.

Methionine residues 24 and 26 of cardiotoxin VII1 from Naja melanoleuca were oxidised to sulphoxides using N-chlorosuccinimide at pH 8.5. The number of equivalents of oxidant required for complete oxidation suggested that the methionine side-chains existed in a relatively "exposed" conformational state in cardiotoxin. The oxidised cardiotoxin was devoid of lethality. It was also non-haemolytic, both on its own and in the presence of phospholipase A2. However, it was still able to precipitate with anti-cardiotoxin antibody. CD studies indicated that the polypeptide backbone conformation was intact in the oxidised cardiotoxin but some perturbation of tyrosine residues was evident. The possibility of a direct or indirect involvement of the methionine residues in the biological activity of the cardiotoxin is discussed.


Bovine thyroxine-binding globulin. Purification and comparison of molecular weight and amino acid composition with human thyroxine-binding globulin.

Bovine and human thyroxine-binding globulin were purified from serum by a three-step purification procedure which comprised affinity chromatography consecutively on thyroxine- and Concanavalin A--Sepharose and finally preparative polyacrylamide gel electrophoresis. The molecular weights of the two proteins were similar (54 000) as well as their carbohydrate contents while some differences in amino acid composition were found. Rabbit antiserum against bovine thyroxine-binding globulin reacted with human thyroxine-binding globulin with no sign of spur formation.


Vitamin A and thyroxine carrier proteins in chicken plasma: steady-state control of the plasma level of free retinol-binding protein and free thyroxine.

1. The binding parameters of prealbumin-2 with retinol-binding protein and thyroxine (T4) revealed the existence of distinct and multiple sites for both retinol-binding protein and T4. 2. From the analysis of binding parameters of retinol-binding protein with prealbumin-2 it is clear that under steady-state conditions about 99% of the holo-retinol-binding protein remains bound to prealbumin-2. 3. Equilibrium dialysis studies on binding properties of thyroid hormones with prealbumin-2 revealed that it has a single high affinity site and three low affinity sites. 4. The occurrence of three carrier proteins for thyroid hormones, thyroxine-binding globulin, prealbumin-2 and albumin has been demonstrated. However, the chicken thyroxine-binding globulin differs from human thyroxine-binding globulin by being relatively less acidic and occurring at a two-fold lower concentration. But the thyroid hormone binding parameters are comparable. 5. Highly sensitive methods were developed for determination of T4 binding capacities of the various proteins and plasma level of total T4 by fractionation of carrier proteins and further quantitatively employing in electrophoresis and equilibrium dialysis. 6. The thyroxine-binding proteins were found to be of two types, one (viz., thyroxine-binding globulin) of great affinity but of low binding capacity, which mainly acts as reservoir of T4, and another (viz., prealbumin-2) of low affinity but of high binding capacity, which can participate predominantly in the control of the free T4 pool.


Tissue distribution of EDTA encapsulated within liposomes containing glycolipids or brain phospholipids.

Multilameller liposomes were prepared with various asialoglycolipids, gangliosides, sialic acid, or brain phospholipids in the liposome membrane and with ethylenediaminetetraacetic acid (EDTA) encapsulated in the aqueous compartments. The liposomes containing glycolipids or sialic acid were prepared from a mixture of phosphatidylcholine, cholesterol, and one of the following test substances: galactocerebroside, glucocerebroside, galactocerebroside sulfate, mixed gangliosides, monosialoganglioside GM1, monosialoganglioside GM2, monosialoganglioside GM3, disialoganglioside GD1a, or sialic acid. The liposomes containing brain phospholipids were mixtures of either sphingomyelin and cholesterol or a brain total phospholipid extract and cholesterol. Distributions of 14C-labeled EDTA were determined in mouse tissues from 15 min to 6 h or 12 h after a single injection of liposome preparation. Liver uptake up encapsulated EDTA was lowest from all liposome preparations containing sialic acid or sialogangliosides, regardless of the amount of sialic acid moiety present or the identity of the particular ganglioside; highest uptake of encapsulated EDTA by liver was from liposomes containing galactocerebroside or brain phospholipids. Lungs and brain took up the largest amounts of EDTA from liposomes containing sphingomyelin and lesser amounts from liposomes containing GD1a. Use of mouse brain phospholipid extract to prepare liposomes did not increase uptake of encapsulated EDTA by the brain. EDTA in liposomes containing monosialogangliosides, brain phospholipids, galactocerebroside, or sialic acid was taken up well by spleen and marrow. Highest thymus uptake of encapsulated EDTA was from liposomes containing GD1a. These results demonstrate that inclusion of sialogangliosides in liposome membranes decreases uptake of liposomes by liver, thus making direction of encapsulated drugs to other organs more feasible. Liposomes containing glycolipids also have potential uses as probes of cell surface receptors.


Association of diamine oxidase and ornithine decarboxylase with maturing cells in rapidly proliferating epithelium.

Diamine oxidase and ornithine decarboxylase activities are shown to have a parallel distribution across rat small intestine mucosa; levels of both enzyme activities are sharply higher in mature cells in the villus tip region than in proliferating cells in the crypt areas. Histidine decarboxylase levels were not measurable in the same cell preparations and aromatic-L-amino-acid decarboxylase activity was distributed in an opposite pattern to diamine oxidase and ornithine decarboxylase. The results suggest that intestinal diamine oxidase could be involved with polyamine metabolism. The new findings for ornithine decarboxylase suggest an in vivo role for polyamines in non-proliferative cells; rat small intestinal mucosa may be an excellent model for investigating the function of polyamines in regenerating cells.


Polysaccharides of crithidia fasciculata. Identification and partial characterization of a cell surface constituent.

A carbohydrate-containing fraction was extracted from the trypanosomatid Crithidia fasciculata by a phenol-water procedure. Ion-exchange chromatography separated this fraction into three components: a polysaccharide which was not retained on the column; RNA which eluted upon addition of salt; and, another polysaccharide which eluted upon addition of detergent. The unretained fraction was shown to be composed solely of D-mannose. The mannan, which was heterodisperse on Sephadex G-100, had an average molecular weight of approx. 14 000 as based on analysis of reducing groups. The detergent-eluted material yielded arabinose and galactose upon acid hydrolysis. The arabinogalactan was excluded from Sephadex G-100 and Sephacryl S-200 molecular sieve columns, suggesting a molecular weight greater than or equal to 200 000. Cell fractionation studies showed the bulk of extractable polysaccharide was associated with a particulate fraction. Further determination of the cellular localization of the polysaccharide was accomplished by employing a specific antiserum prepared from rabbits immunized with the polysaccharide extract. The cell surface localization of the arabinogalactan was demonstrated by cell agglutination studies as well as immunocytochemical techniques using fluorescein and ferritin conjugated antibodies.


Prevention of the cortical reaction in fertilized sea urchin eggs by injection of calcium-chelating ligands.

Eggs from the sea urchin, Lytechinus pictus, were injected with either EGTA or EDTA, and were subsequently fertilized. EGTA prevented cortical vesicle discharge and formation of the fertilization membrane. EDTA had either no effect, or sometimes retarded the elevation of the fertilization membrane, or reduced the percentage of eggs with elevated membranes. Theoretical considerations lead to estimates of the probable effects of EGTA and EDTA on the internally released calcium which triggers the cortical reaction. Whether or not cytoplasmic calcium buffers are considered, it is concluded: (1) that normally several times the threshold calcium concentration for the cortical reaction is released into a subsurface space; (2) that if a rapidly-equilibrating high-affinity buffer is present, it is locally saturated by the calcium released internally; (3) the injected EDTA reduces the subsurface free calcium concentration normally reached to approximately threshold for the cortical reaction, while injected EGTA reduces the calcium concentration to below this threshold; and (4) a rise in the internal ionic calcium concentration is a necessary step in the activation of the cortical reaction at fertilization.


Nitrogen fixation and hydrogen metabolism in photosynthetic bacteria.

The photosynthetic bacteria are found in a wide range of specialized aquatic environments. These bacteria represent important members of the microbial community since they are capable of carrying out two of the most important processes on earth, namely, photosynthesis and nitrogen fixation, at the expense of solar energy. Since the discovery that these bacteria could fix atmospheric nitrogen, there has been an intensification of studies relating to both the biochemistry and physiology of this process. The practical importance of this field is emphasized by a consideration of the tremendous energy input required for the production of artificial nitrogenous fertilizer. The present communication aims to briefly review the current state of knowledge relating to certain aspects of nitrogen fixation by the photosynthetic bacteria. The topics that will be discussed include a general survey of the nitrogenase system in the various photosynthetic bacteria, the regulation of both nitrogenase biosynthesis and activity, recent advances in the genetics of the nitrogen fixing system, and the hydrogen cycle in these bacteria. In addition, a brief discussion of some of some of the possible practical applications provided by the photosynthetic bacteria will be presented.


Hydrogen metabolism in blue-green algae.

This manuscript reviews the literature on hydrogen metabolism in blue-green algae and reports some new data from this laboratory. H2-formation by intact cells is found to be catalyzed exclusively by nitrogenase. Its rate appears to be variable from strain to strain used byt is--in our hands--very small. Therefore, blue-green algae are presumably of limited value in projects of solar energy conversion to form molecular hydrogen. These organisms are also able to consume the gas in a reaction catalysed by hydrogenase. Hydrogen is mainly consumed in an oxygen dependent reaction, as in aerobic nitrogen fixing bacteria. It can also serve as an electron donor for nitrogen fixation under certain physiological conditions. In experiments with a cell-free preparation, hydrogenase is found to be membrane-bound. The enzyme is characterized with respect to its specifity towards electron donors and acceptors.


[Isolation and properties of human immunoglobulin-peroxidase complex].

The complexes of human immunoglobulin G (IgG) with peroxidase produced by a two-step synthesis using glutaraldehyde retain high enzymatic and immunochemical activities. The effectiveness of the complex formation depends on the concentration of glutaraldehyde used for enzyme modification. Optimal molar ratios of the constituent components during the synthesis of the complex and localization of the enzyme on the IgG molecule are discussed. Preliminary heating of IgG or the overall complex at 50 degrees C results in an increase of the complex stability (20-fold) under storage.


Relationship between anorectic and reinforcing properties of appetite suppressant drugs: implications for assessment of abuse liability.

A quantitative ratio measure was developed which permitted comparisons between the reinforcing and anorectic potency of eight phenylethylamine anorectics and cocaine in laboratory baboons. The ordering of these compounds based upon this ratio bears a reasonable correspondence to clinical drug evaluations. The measure may provide information for preclinical evaluation of relative abuse potential of anorectic drugs.


[Several features of the antioxidant action of chemical carcinogens].

Comparative studies of antioxidative effects of phenole inhibitors (vitamine E) amino-and sulfur-containing radioprotectors, and chemical cancerogens on oxidation of unsatured fatty acid were carried out. Some polycyclic hydrocarbons and azo-compounds produce a prolonged and stable decrease of peroxide accumulation rate in oxidized oleic acid. Due to this property in the in vivo systems chemical cancerogenes can induce prolonged stable changes in the parameters of vitally important redox processes.


[Kinetics, mechanism and thermodynamics of cyanophage A-1 adsorption onto algal host cells].

It is found that adsorption kinetics of cyanophage A-1 on algae Anabaena variabilis cells is more complex than the reaction kinetics of the first order. An analysis of virus adsorption curves on cells and some other characteristics of this process have shown that virus A-1 is absorved on the algae-host cells according to adsorption concurrent model. Some thermodynamic characteristics of the process studied are calculated. Their values point to enzymatic character of the reaction of virus fastening to the algae.


Logistic problems of artificial nutrition.

The future of artificial nutrition, both enteral and parenteral, depends upon further simplification of the methods for preparation of nutritive mixtures, as well as, maintaining the motivation and special training of nursing teams with regard to problems of asepsis. The range of clinical and biological will research only widen if technical and practical matters are handled with surgical rigour.


[Nature of changes in the level of steroid hormones and their precursors in peripheral blood of Papio monkeys under stress].

The radioimmunological method was applied to determination of changes in the peripheral blood plasma level of 12 steroids in male Papio hamadryas under immobilization and surgical stress. Androgen content decreased, and the concentration of steroid hormone precursors and hydrocortisone blood plasma content rose in response to stress. These changes were in contraphase with the circadian steroid rhythms. The most objective and sensitive criteria of the stress situation evaluation were decrease of testosterone and dihydrotestosterone level, increase of pregnenolone concentration, as well as of 17-alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone in the blood plasma.


[Contractile reaction of the myocardium of patients with heart diseases to chemical scarification of cell membranes].

Strips of the myocardium from the auricula atria of patients suffering from mitral stenosis (MS) and septal defects of the heart (SDH) removed during the operation were treated with ethylenediaminetetraacetic acid (DETA)--3mM--to increase the cell membrane permeability (scarification). The mechanical response of the contractile proteins to the change in the Ca2+ was recorded in the ethylene-hexaaminetetraacetic acid (EHTA)--3mM--against the background of increased membrane permeability to the Ca-EHTA complex permitting to regulate Ca2+ concentration in myofibrillae from 10(-9) to 10(-4)M. As shown, with the same threshold concentrations (5.10(-8)M) and saturation concentrations (10(-4)M) of Ca2+ the strips from the patients with MS developed the maximal tension per cross section unit of the strip half as great as the preparations from patients with SDH, this indicating a possible affection of the contractile proteins in the hearts of patients with MS. The ratio between the tension amplitudes under conditions of a complete calcium activation of the contractile proteins and a single isometric contraction for the preparations obtained from the patients with MS was 8 to 10, and with SDH--from 4 to 5. It is supposed that this was the result of more pronounced changes in the apparatus of electromechanical conjugation of the myocardium of patients suffering from MS.


[Effect of combined administration of hydrocortisone and EDTA on the number of the antibody-producing cells in the spleen of mice immunized with sheep erythrocytes].

Experiments on mouse hybrids (CBA X C57BL)F1I indicated that injection of hydrocortisone in a dose of 1 mg/mouse 24 hours after the immunization with sheep red blood cells against the background of multiple EDTA injection resulted in a relative reduction of the plaque-forming cells in the spleen--more than 6-fold in comparison with control, and more than 3-fold in comparison with the effect of hydrocortisone or EDTA alone. This may possibly be the consequence of a more intensive hydrocortisone incorporation under conditions of prolonged hypocalciemic action of EDTA complexon.


A new experimental model of systemic connective tissue disease in immunized rabbit.

In rabbit, the immumizations with whole Mycobacterium Tuberculosis injected intradermally and its crude cytoplasmic W.S.E. injected intraarticulary induce not only a self-perpetuating synovitis in the stimulated knee but also chronic systemic lesions of connective tissue (non-stimulated knee, both shoulders, aortic artery adventitial valvular endocardium, liver, kidneys and lungs). W.S.E. stimulates precipitating antibody synthesis, skin reaction and lymphoblastic transformation of lymphocytes in vitro. Furthermore, rabbits develop tuberculin skin test and lymphocytic response to P.P.D. The intensity of inflammation in stimulated knee is in direct ratio to intensities of humoral and cellular immunological responses. On the contrary, the incidence of systemic lesions is in inverse ratio to immune responses and intensity of inflammation in stimulated knee.


[Physico-chemical properties of microbial antigens and the immuno-allergic tests].

Experiments were conducted on guinea pigs sensitized by the delayed and immediate types of allergy. Different antigens obtained from the strain of Brucella abortus BA-19 were used for sensitization and the resolving action. Comparison of the resolving properties of the corpuscular, soluble (ultrasound treated) antigens and purified protein fractions, polysaccharide and RNA was carried out in the skin reactions of the immediate and delayed type, passive skin anaphylaxis, acute anaphylactic shock, and the Schults-Dale test. Immediate reactions to the purified protein fraction were weaker than those to the whole soluble antigen, by which the animals were sensitized. Polysaccharide and the RNA-fractions proved to be inactive in the allergic reactions.


[Various aspects of transplacental blastomogenesis in rabbits].

Transplacental blastomogenic action of different carcinogenic agents (ethylnitrosourea--ENU), methylnitrosourea--MNU, dimethylbenzanthracene--DMBA, and benz(a)pyrene--BP) was studied in rabbits. As revealed, ENU had the greatest blastomogenic activity and an expressed neurotropic action. Relative tropism to different tissues characteristic of some carcinogenic agents during their action on adult organism was not always expressed in transplacental blastomogenesis, Study of the influence of different modifying factors (organospecific immunization, chronic irritation of the peripheral nerve, injection of the MNU) on the realization of transplacental blastomogenesis showed that their postnatal use stimulated mostly the appearance of the peripheral nerve timours in the offspring rabbits (MNU inhibited the development of tumours).


[Nonspecificity of antiviral protein action].

The authors studied the antiviral activity of the informative RNA of antiviral protein (M-RNA AVP) isolated from the cells following superinduction of interferon in them for the purpose of ascertaining the action specificity of the product of their translation--AVP. Following the administration of M-RAN AVP a marked (from 1 to 5 lg PFU/mil) reduction of the infectious titres was observed in the homologous and heterologous cells. RNA preparations from control (noninduced) cells possessed a weak (0.4--0.1 lg PFU/mil) antiviral activity.


An investigation of a proposed linkage between the Rhesus and Gm systems.

An investigation of 1088 unrelated British people to look for an association between alleles of the Rhesus blood group system and those of the Gm system gave the result expected for totally independent loci.


American trypanosomiasis (Chagas' disease) in the Caribbean.

Chagas' disease (American trypanosomiasis) is endemic in nearly all Central and South American countries facing the Caribbean basin. Since 1960, reports from the islands of Aruba, Curaçao, Jamaica, and Trinidad have confirmed the presence of Trypanosoma cruzi, blood-sucking triatomine bugs, and wild animals infected with the parasite. It was also established that T. cruzi, triatomine bugs, infected wild animal reservoirs, and people with a positive serologic test for T. cruzi antibodies are to be found in Belize, the last country in Central America once thought to be free of Chagas' disease.


Pituitary responsiveness to LHRH and TRH in adolescent girls.

Puberty is characterized by a progressive maturation of the hypothalamus-pituitary gonadal axis which, in girls results in menarche. The first menstrual cycles are usually irregular and anovulatory, and the subtle positive and negative regulation of sex steroids on the hypothalamus-pituitary axis has probably not reached adult maturity. An investigation has been carried out in 99 normal adolescent girls, divided into 3 groups: 1-2, 3-4 and 5 years after menarche, by measuring basal hormonal values as well as the responses to LHRH and TRH during the follicular and luteal phases. Basal FSH and LH values reached adult levels after the second year of menarche, while FSH and LH responses to 50microgram LHRH showed a regular and progressive increase from 1 to 5 years post-menarche, resulting, in the 5-year group and in spite of the half dose received, in definitely higher FSH and LH responses than those observed in the adult women after 100 microgram LHRH. This enhanced pituitary responsiveness to LHRH is due to still progressively increasing estradiol and progesterone secretions, the latter hormone remaining still lower than in the adults. Basal prolactin levels were significantly higher than those found in adult women with a slightly increased prolactin response to TRH and an exaggerated one of TSH, with normal T3 and T4 levels. These data show that from the onset of menarche to the complex and subtle adult menstrual cycle regulation, there is a continuing maturation of the hypothalamus-pituitary axis of the gonads which lasts approximately 5 years. It is characterized by increasing E2 secretion, low progesterone secretion and slightly increased prolactin levels, with a frequently impaired luteal phase. The enhanced pituitary sensitivity to releasing hormones is due to the positive feedback mechanism of E2 which is not yet associated with adequate progesterone secretion for a negative feedback, as in adult women. Thus, adolescence is still a maturation period, the onset of ovulation being the final step in this development.


[Radioimmunological aspects of neuropeptides].

Immunological aspects of neurosecretory peptides are relevant to antibody generation, labelling of peptides for radioimmunoassays and in particular the metabolism of neuropeptides. Antibodies were generally produced by adsorption or polymerization (using different approaches and various coupling agents) of peptides with intrinsic antigenic molecules preceding their administration to recepient animals (rats, guinea pigs, rabbits and sheep) with adjuvants. Antibodies were also obtained by injecting peptides alone with or without adjuvants. However, independent of the recipient species, the highest specific or nonspecific antibody titers were obtained by the former method. Up to now, only 3H-peptides or 125I-peptides or derivatives were used as tracers in RIAs. Highest sensitivities were generally obtained when using 125I-peptides. However, 125I-peptides may be adsorbed ("false titers") to some antiserum with sufficient specificity in terms of displacement by structural analogues of the peptide but with a loss of sensitivity. Finally, large molecular forms, cross-reacting with the antibodies prepared with different methods and peptidasic activities must be taken into account. These topics are presented with data on LHRH, TRH and substance P derived from our experiments and from those of other investigators.


Stimulation of acetylcholine output from brain slices caused by the ionophores BrX-537A and A23187.

1 The effect of two ionophores, BrX-537A (Bromolasolacid) and A 23187, on acetylcholine (ACh) output from brain slices was studied. 2 The slices were prepared from rat cerebral cortex, incubated in Krebs solution containing physostigmine and ACh output determined by bioassay. 3 Both ionophores enhanced ACh output. BrX-537A exerted its maximal effect, a six fold increase, at a concentration of 1.8 micron, while A 23187 caused a three fold increase at a concentration of 58 micron. 4 When the slices were incubated in a Ca-free medium, the effect of A 23187 on ACh output was only reduced, BrX-537A was abolished while that of BrX-537A was also active when disodium edetate (EDTA) was added to the the Ca-free medium. 5 The activity of BrX-537A was not affected by the presence of tetrodotoxin in the incubation medium. 6 The stimulation of ACh output elicited by KCl (25 mM) was increased further by hyoscine, but not by BrX-537A. Hyoscine however had no effect when ACh output was stimulated by BrX-537A. 7 The effect of BrX-537A on ACh output was potentiated by the addition of Mg2+ (9.3 mM) to the incubation medium and was reduced in a Mg-free medium. 8 It is concluded that A 23187 stimulates ACh output by transporting extracellular Ca2+ into cholinergic nerve endings. The effect of BrX-537A does not depend only on Ca2+ but also on other mechanisms.


Diminished cellular immunity due to impaired nutrition in oesophageal carcinoma.

The nutritional status of 15 Negro patients suffering from unresectable carcinoma of the midthoracic oesophagus was evaluated before and after palliative pulsion intubation. All were shown to be in negative nitrogen balance and to have a compromised non-specific cellular immune response. Correction of protein-calorie malnutrition and the achievement of positive nitrogen balance were associated with an increase in absolute lymphocyte and T lymphocyte numbers and a significant increase in lymphocyte response to PHA. The improvement in immunological reactivity occurred without any attempt at therapeutic reduction in tumour bulk.


Vitamins in intravenous feeding: a study of water-soluble vitamins and folate in critically ill patients receiving intravenous nutrition.

Red cell B vitamins, folate and white cell vitamin C were measured in a group of critically ill surgical patients before and following a course of intravenous nutrition. Patients received a widely used vitamin supplementation regimen in the form of one ampoule of water-soluble vitamins daily and recommended doses of intramuscular folate, vitamin B12 and vitamin K weekly. This regimen was adequate to maintain tissue levels of the water-soluble vitamins and folate. Patients with initially low values had normal values at the end of the treatment period.


Muscle chemistry of critically ill surgical patients and the effects of a course of intravenous nutrition.

The water, electrolyte and nitrogen contents of muscle were measured in 15 critically ill surgical patients before and after a course (approximately 2 weeks) of intravenous nutrition and in 8 normal individuals. The muscle from the surgical patients contained a significantly increased ratio of water to fat-free dry weight (P less than 0.01) due to an increase in the proportion of extracellular to intracellular water, and this was not corrected by intravenous nutrition. These changes could be due to an accumulation of extracellular fluid alone or to a loss of cell cytoplasm or a loss of whole muscle fibres. Intracellular chemistry was normal in the ill surgical patients and was not changed by intravenous nutrition.


Effect of gastrointestinal hormone infusions of lower oesophageal competence of rhesus monkeys.

The lower oesophageal high pressure zone (HPZ) was studied in 5 non-refluxing and 3 refluxing Rhesus monkeys. The changes in HPZ and reflux status in response to infusion of various doses of secretin, cholecystokinin and glucagon were measured in all animals, and, in the 5 non-refluxing monkeys, after oesophagogastrectomy with replacement of the lower oesophagus by a stomach tube. All three hormones consistently produced a transient decrease in the HPZ pressure. The only change in response following oesophagagastrectomy and gastric tube replacement was a significant delay in the response to each hormone. Neither hormone infusion nor operation altered gastro-oesophageal reflux status. It appears that lower oesophageal competence in primates is more dependent on the presence of narrow, muscular, intra-abdominal tube than on a specialized segment of the lower oesophagus.


Medical care in a tropical national reference and teaching hospital: outline study of cost-effectivenees.

During a 28-day prospective audit the cost-effectiveness of treatment in three types of medical wards in a large tropical teaching hospital was assessed. Patients with chronic diseases such as rheumatic heart disease were more expensive to treat than those with acute, curable illnesses such as malaria. It was concluded that the cost of providing treatment could not be reduced without affecting standards of medical care. The expense of running such a hospital might also be justified by its importnat function as a teaching hospital.


Prevention of Rh haemolytic disease.

Between 1970 and 1976 in the Yorkshire region the incidence of Rh antibodies in Rh-negative pregnant women fell by 70%. This decrease occurred in both old (long-standing) and new (first-affected) cases, which emphasised that the reduction in numbers was as much due to fewer pregnancies among Rh-negative mothers as to administration of anti-D immunoglobulin. Nevertheless, the incidence has begun to level out. The continued incidence of first-affected cases is caused by three main factors: failure of administration of anti-D immunoglobulin after normal deliveries and abortions; a steady incidence of antibodies in primigravidae; and cases in which administration of anti-D immunoglobulin had failed to protect. Administering anti-D antenatally might reduce the incidence of new cases among primigravidae who are sensitised before anti-D is normally given. Even without routine antenatal administration of anti-D, the incidence of severely affected Rh babies in the Yorkshire region could be reduced to one or two isolated cases a year in a population of three to four million by administering anti-D after all Rh-negative deliveries and after every abortion.


Pressure enhancement of the depressant effect of halothane on cilial beat.

In order to test the applicability of the critical volume hypothesis of anaesthetic action to the side effects of anaesthesia, we have studied the pressure-anaesthetic interactions on cilial beat. The swimming speed of Tetrahymena pyriformis was determined at one and 137 atmospheres with 0 to 4 per cent halothane. The pressure and anaesthetic effects were synergistic with the halothane dose-response curve being shifted to the left and increased in slope at the high pressure, although high pressure alone had no significant effect. These results are contrary to the predictions of the critical volume hypothesis and appear to demarcate the narcotic effect of anaesthetics from the type of molecular interaction which is concerned in the effect on cilial beat.