The neuromuscular blocking activity of aminodeoxykanamycin as compared with that of other aminoglycoside antibiotics. Aminodeoxykanamycin (Kaneudomycin) as well as other members of the aminoglycoside antibiotics, has an action at the neuromuscular junction. Kanendomycin was found to be five times less potent than gentamycin, as far as their neuromuscular blocking action on the rat diaphragm is concerned. The neuromuscular blocking action on the rat diaphragm is concerned. The neuromuscular blockade produced by Kanendomycin is not reversed by neostigmine but only by calcium chloride.


Histocompatibility antigens and effects of neuroactive drugs on phytohaemagglutinin stimulation of lymphocytes in vitro. The effects of a psychopharmacological agent, sulpiride, and of some neuromediators, dopamine, norepinephrine and propranolol, on the uptake of 3H-thymidine by lymphocytes stimulated in vitro with phytohaemagglutinin (PHA) were studied. The lymphoctes were obtained from two populations of subjects, one with HLA-AL CRAG antigens of the HLA-SD series and one without. We found that the presence of the CRAG antigens in the lymphocytes led in the presence of the various drugs to behaviour different from what was seen when the antigens were not present. When the two groups were pooled, PHA lymphocytes activation was inhibited by dopamine, sulpiride, and propranolol and was not effected by norepinephrine.


[Clinical study with a new antihyperlipemic combination]. 70 patients with hyperlipemias of various types were treated perorally with 350 mg Mg-chlorophenoxyisobutyrate, and 250 mg of mesoinositol-hexanicotinate (Atroplex) three times daily. This treatment led to a statistically significant decrease in the respective elevated serum lipid levels. The serum total cholesterol level was decreased by 20.3% in Type IIa and by 19.8% in Type IIb, the triglyceride level was decreased by 27.7% in Type IIb and by 38.9% in Type IV. The phosphatide level was lowered by 14.6% in Type IIa, by 15.7% in Type IIb and by 15.9% in Type IV; the cholesterol-phospholipid ratio could be shifted in favour of the phospholipids in Type IIa and IIb. Glucose tolerance and systolic blood pressure were not influenced, but in Type IV a statistically significant decrease in the diastolic pressure and in serum uric acid level was noticed. Prothrombine time and normal fibrinogen levels remained unchanged, elevated fibrinogen levels returned to normal. Elevations of serum enzymes and of serum bilirubin were noted which were minimal and reversible, liver toxicity could not be noticed. Subjective symptoms of peripheral circulatory disturbances improved markedly in 10 cases, the most striking side effect was the occurrence of gastrointestinal imcompatibility, which in one case forced to discontinue the medication. The dosage of the single components is this combined therapy is significantly lower than the doses usually used for clofibrate or mesoinositol-hexanicotinate.


Plasma concentrations of isosorbide dinitrate after oral administration of a sustained-release formulation to human subjects. 1. A peak of mean plasma concentrations of isosorbide dinitrate of 5.8 ng/ml was reached at 0.5 h after a single oral dose of 5 mg in a standard tablet formulation. Thereafter mean concentrations declined with a half-life of about 48 min. 2. A peak of mean concentrations of isosorbide dinitrate of 3.2 ng/ml was reached at 2--4 h after a single oral dose of 20mg in a sustained-realease capsule formulation (Iso Mack Retard). Thereafter mean concentrations declined by about twofold during 6 h and were still detectable at 12 h after dosing. 3. When corrected by dose/bodyweight variations, the mean area under the isosorbide dinitrate plasma concentration curve from the sustained-release capule was 76% of that from the standard tablet and this formulation-related difference in bioavailability was statistically significant (p less than 0.05). 4. The results showed that sustained-release formulation is a useful way to maintain plasma concentrations of isosorbide dinitrate for several hours.


Pharmacokinetic and metabolic pathways of dimethophrine in man. Pharmacokinetics and metabolism of dimethophrine labelled with tritium have been investigated on 5 subjects treated orally with a single dose of 100 mg. The results obtained have shown that: 1. the absorption and urinary elimination are rather slow; 2. no metabolic transfromation of the drug occurs, except conjugation.


The effect of magnesiumaspartate on preservation of the rat liver. 1. Isolated rat livers reperfused with an oxygenated isotonic Mg-aspartate or saline solution and stored 1 h at 36 degrees C, 4 h at 22 degrees C or 12 h at 6 degrees C were reperfused at 37 degrees C 150 min with a Krebs-Henseleit solution containing bovine albumin and erthrocytes gased with a 95% O2-5% CO2 gas mixture. 2. Light- and electronmicroscopic studies revealed minor changes after storage, whereas in the reperfused livers a focal distribution of well preserved and disintegrated hepatocytes was observed. 3. During storage the sum of adenine nucleotides in general decreased markedly paralleled by a significant rise of the lactate/pyruvate and hydroxybutyrate/acetoacetate ratios and pronounced breakdown of glycogen. Oxidative phosphorylation was resumed upon reperfusion resulting in de novo synthesis of ATP and ADP. The lactatelpyruvate and hydroxybutyrate/acetoacetate ratios normalized, whereas a resynthesis of glycogen was missing. 4. No conclusive evidence of a protective Mg-effect as observed in induced cardiac arrest has been obtained, probably due to structural and metabolic differences between the two organs and microcirculatory disorders as has been demonstrated by measurements of oxygen uptake using the multiwire electrode.


[Chemotherapeutically effective nitro compounds. 3rd communication: nitropyridines, nitroimidazopyridines and related compounds (author's transl)]. New 2-nitropyridines and 3-nitropyridines, and 3-nitroimidazo-[1,2-a]-pyridines and related compounds (together 106) were synthesized and tested for their chemotherapeutic efficacy against trichomonads, amoebas and other organisms, such as Eimeria tenella, bacteria, fungi, helminths. Several 2-nitropyridines revelaed a detectable systemic effect against Entamoeba histolytica (extraintestinal amoebiasis of the golden hamster) and also a weak activity against Trichomonas fetus in the NMRI-mouse. Only a few 3-nitropyridines showed a marked systemic effect against trichomonads. Of the 3-nitroimidazo-[1,2-a]-pyridines, only the electroneutral carboxylic acid amide group exhibited a pronounced activity, exclusively against trichomonads; however, the activity was nullified again by electronegative, electropositive and other electroneutral substituents. As they were not superior in chemotherapeutic respect compared to the known standard preparation (metronidazole), no further tests were carried out with the most effective compounds.


Determination of verapamil in human plasma by mass fragmentography using stable isotope-labelled verapamil as internal standard. In the present investigation a mass fragmentographic procedure for the quantitative determination of verapamil in human plasma was developed which makes use of the principle of mass spectrometry and of isotopic dilution: a known amount of isotopically labelled standard ([13C, 2H2]-verapamil) is added to the plasma sample. After an effective extraction procedure the ratio of the main fragments of verapamil (m/e 303) and the labelled standard (m/e 306) is measured by mass fragmentography. The lower limit of detection is at 1 ng/ml for plasma and at 10 pg/injection for pure verapamil. The precision was found to be between 3.4% and 14.4%, depending on the range (32.7 ng/ml and 2.2 ng/ml, resp.) of the concentration of verapamil in plasma.


Antimicrobial evaluation of cefoxitin: a new semisynthetic cephamycin. Comparative studies with cefazolin and cefalotin. Antimicrobial activity of 3-carbamoyloxymethyl-7-alpha-methoxy-7-[2-(2-thienyl)-acetamido]-3-cephem-4-carboxylic acid (cefoxitin), a new semisynthetic cephamycin antibiotic, was studied in comparison with that of cefazolin and cefalotin. Cefoxitin exhibited antibacterial activity against both gramnegative and gram-positive bacteria, and its action was bactericidal. Against gram-negative bacteria, cefoxitin was highly active as well as cefazolin, and more active than cefalotin. Especially, cefoxitin was highly active not only against strains of clinical isolates of indole-positive Proteus and S. marcescens but also against those of E. coli and P. mirabilis which were resistant to cefazolin and/or cefalotin, respectively. In addition, cefoxitin was effective against the strains resistant to beta-lactam antibiotics including cefazolin and cefalotin. Cefoxitin was hardly active against the strains of E. cloacae and P. aeruginosa, similar to cefazolin and cefalotin. Against gram-postive bacteria, cefoxitin was less active than cefazolin and cefalotin. In protection tests in mice, cefoxitin and cefazolin were more effective against infection with E. coli than cefalotin. Furthermore, cefoxitin was more active against infections with S. marcescens and P. morgani than the other antibiotics. Cefoxitin, like cefalotin, was less effective against infection with S. aureus than cefazolin. Cefoxitin was highly resistant to hydrolysis by beta-lactamases derived from the organisms insusceptible to the antibiotic. This fact revealed that the resistance of the organisms to cefoxitin may be in part due to factors other than beta-lactamase inactivation.


[Assembly and function of organized enzymes (author's transl)]. When different enzymes form complexes with one another they gain new capabilities of function. Tryptophan synthase is discussed as an illustrative example in which formation of the complex leads to mutual activation of the component subunits. Kinetic studies show that conformational changes play an important role in this process. As the extreme case of self-organisation, structural genes of different enzymes might have been fused in the course of evolution, giving rise to multifunctional enzymes.


[Collagen biosynthesis as an example for the regulation of gene expression in mesenchymal cells (author's transl)]. The polymorphism of collagen was the initial observation which stimulated the interest in the regulation of the gene expression of this eucaryotic protein. In the first set of experiments it was shown that a fibroblast from fetal skin possesses the capability to synthesize both type I and type III collagen at the same time. In a second line of investigations, evidence was obtained that in the course of the degenerative osteoarthrosis chondrocytes switch from synthesis of type II collagen to synthesis of type I collagen. A similar observation was made when enzymatically isolated chondrocytes from the sterna of embryonic chicken were grown under tissue culture conditions. This change in synthesis probably reflects a change in gene regulation which might be caused by an as yet unknown disturbance in the cell matrix interaction.


[The biological clock: circadian organization of the cell (author's transl)]. Unicellular systems, and particularly individual cells, are advantageous in investigating the molecular mechanism of the circadian rhythm. The greeen alga Acetabularia has proven to be a uniquely suitable organism. Experiments are described which indicate that the circadian rhythm is due to a sequence of events which are casually interrelated. A model is presented which is based on a two-step mechanism, the first step of which is the synthesis of "essential polypeptides" on 80 S ribosomes. In a second step these polypeptides are consumed. The function of the "essential polypeptides" is to change a membrane component of the circadian clock. The membrane participates in a feed-back mechanism which produces a periodic alteration of the rate of synthesis of "essential polypeptides" and of photosynthesis. It is possible to draw parallels between this circadian rhythm model and other repetitive and non-repetitive types of temporal organization within the cell, e.g., the cell cycle; however, it must be stressed that in the case of the circadian rhythm, much stronger and more efficient mechanisms exist to keep the period constant. This is true particularly for temperature compensation. Such a conservatism is understandable if one recalls that during evolution, the circadian rhythm represents an adaptive advantage which permits the organism to adjust it activities in advance to periodic processes resulting from the earth's rotation.


[Correlation between structure and pathogenicity of myxoviruses (author's transl)]. Myxoviruses (ortho- and paramyxoviruses) possess on their surface two virus-specific glycoproteins, the functions of which are largely understood; These glycoproteins are synthesized on the rought endoplasmic reticulum, and during their transport to the plasma membrane on smooth intracellular membranes, they undergo modification through proteolytic cleavage. In this way, the orthomyxovirus hemagllutinin is converted from a high-molecular weight form (HA) into two smaller cleavage products (HA1 and HA2). With the paramyxoviruses, the glycoprotein F, which is responsible for fusion and hemolysis, is derived from proteolytic cleavage of a precursor, F0. Furthermore, with a few strains of avirulent NDV, a precursor of the hemagglutinin-neuraminidase complex, (HN0), has been identified which again, as a result of proteolysis, undergoes cleavage to HN. Whether cleavage takes place is as much dependent on the structure of the glycoprotein as on the host cell type. Proteolytic cleavage is indeed not necessary for virus particle production but is required for infectivity. Virus particles which possess the uncleaved glycoproteins may be activated by in vitro treatment with trypsin. As evidenced by experiments with orthomyxovirus recombinants, the glycoproteins alone do not determine the pathogenicity of the viruses. With paramyxoviruses, the pathogenic and apathogenic strains show clear differences in their host range spectrum which is directly related to the sensitivity of their glycoproteins twoard proteases. These observations provide an initial sketch for the molecular basis of infectivity and pathogenicity with myxoviruses.


[Structure-activity relationships of bronchospasmolytic beta-phenylethyl-aminoalkyl-xanthines (author's transl)]. Structure-activity relationships of 90 bronchospasmolytic compenylethyl-aminoalkyl-xanthines are reported. Particularly the influence of substituents in the phenyl moiety as well as of the carbon bridge between the xanthine residue and the beta-phenylethylamine moiety is described. 2. A method is shown for the selection of one optimally bronchospasmolytic substance from many potential compounds synthetised via multiple screening steps to profound biological studies.


[Synthesis of radioactively labelled reproterol hydrochloride (author's transl)]. Synthesis of radioactively labelled 7-(3-[2-(3,5-dihydroxy-phenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol) as needed for pharmacokinetic examinations, is described. The 14C-malonic diethyl ester was proven to be the suitable starting compound. The synthesis of the tritium-labelled reproterol is briefly described.


[Studies on pharmacokinetics and biotransformation of reproterol in animal and man (author's transl)]. Investigations on the pharmacokinetics and biotransformation in the rat, dog, rabbit and in humans were performed with 3H-or 14C-labelled 7-(3-[2-(3,5-dihydroxyphenyl)-2-hydroxy-ethlamino]-propyl)-theophylline (reproterol, Bronchospasmin). Following i.v. administration of reproterol, a similar course of the plasma levels as shown in both rat and dog. After oral administration to the rat, elimination occurs within 2 h following application; in the dog, however, a relatively constant plasma level persists for up to 24 h, which is then reduced during an elimination half-life of 12.4 h. Following i.v. as well as  oral administration to the rabbit, phases of distribution and elimination persist over a  considerable length of time. Plasma levels following oral administration remain relatively constant during a time period of 8--30 h, after which they decrease with a half-life of 70 h. Renal elimination in the dog and rabbit after i.v. application seems to be the main route of excretion (dog 57%, rabbit 66%), while in  the rat there is 58% fecal elimination. Absorption ratios following oral administration amount to 13% in the rabbit and 18% in the rat and dog. The absorption ration in the rat following intratracheal application reaches 90%. This was particularly important in view of the anticipated use of reproterol as an aerosol. Tests on the quantitative organic distribution further showed that in the rat, the lund tissue has a particular affinity to reproterol. In man following i.v. administration, reproterol is rapidly distributed and eliminated. The highest plasma level reached within 2 h after oral administration, correlates well with the initial plasma level following i.v. administration. A great similarity was shown for the reproterol metabolism in rat, dog, rabbit and man. With complete metabolization, the same main metabolite is always formed.


[Synthesis of bronchospasmolytically effective beta phenylethyl-aminoalkyl-xanthines]. New theophylline and theobromine derivatives are synthetized from the beta-phenylethylaminoalkyl-xanthines, whose phenyl substituent is substitutent by one or two hydroxyl groups and partially also by other substituents. Different methods of synthesis are described, among them the production of the bronchospasmolytic 7-(3-[2-(3,5-dihydroxyphenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol-HCl).


[Toxicological investigation of reproterol (author's transl)]. Only slight toxicity of 7-(3-[2-(3,5-dihydroxyphenyl-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol, Bronchospasmin) was shown in the examination of acute, subacute and chronic trials on various animal species with different modes of application. Slight side-effects noted with high toxically active dosages correspond with those of other well-known beta-sympathicomimetics. No influence on the pre-,peri- and postnatal development could be proven with doses tolerated by the parent animals.


[Effects of the new brondilatator reproterol on the cardiac function during treatment of bronchial asthma and chronic obstructive bronchitis (author's transl)]. The new beta-adrenergic phenylethy-aminoalkyl-xanthine derivative 7-(3-[2-(3,5-dihydroxyphenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol, Bronchospasmin) was tested in two patient groups afflicted with bronchial asthma or chronic obstructive bronchitis. Neither  single i.v. administration nor single and 4-week long-term application of blood pressure or ECG tracings. Dosages of i.v. 60 and 90 mug, single peroral administration of 20 mg or long-term therapy with 60 mg in either 3 or 6 daily doses, definitely and significantly improved disturbances in the pulmonary ventilation (Rt, EGV, FEV1). This new preparation represents a predominantly beta2-mimetic  broncholysis as well as the absence of cardiovascular side effects.


[The bronchdilating action of reproterol in patients with bronchial asthma and chronic obstructive bronchitis (author's transl)]. In a comparative study, two groups of patients suffering from bronchial asthma or chronic obstructive bronchitis were tested with the new broncholytic substance 7-(3-[2/24/k-dihydroxyphenyl-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol, Bronchspasmin) versus the well proven drug orciprenaline. Both preparations were administered for four weeks in doses of 3 x 20 mg/day (some patients received 6 x 10 mg/day). Different variables of the lung function were examined twice weekly prior to and 1 hr following ingestion of the substance (FVC, FEV1, Rt, IGV, Palpha02). On the basis of findings in above variables, both reproterol and orciprenaline showed very good and significant broncholytic effects. The efficacy of reproterol, however, proved to be significantly superior to that of orciprenaline. This also has been confirmed in subjective reports of patients with regard to strength and duration of alleviation of their respiratory distress. Palpitation, slight tremor of the fingers, restlessness, pressure in the head and dizziness were mentioned as side effects. These symptoms occurred fairly often with orciprenaline, but relatively seldom with reproterol. This difference between the preparations was highly significant. Following four weeks of administration, no tachyphylaxis was observed. In view of the submitted results, reproterol represents, no doubt, a considerable addition to the presently available therapeutic collection of remedies for the treatment of obstructive airways diseases.


[Studies on the onset of effect of reproterol following inhalation from a metered aerosol (author's transl)]. According to a uniform trial procedure, the broncholytic efficacy of the new beta2-adrenergic 7-(3-[2-(3,5-dihydroxyphenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol, Bronchospasmin) was tested in a total of 21 patients afflicted with airways obstruction in two lungfunction laboratories. The IGV, Ras and SGaw were calculated by bodyplethysmography before and 1,3 and  5 min following of 2 puffs from an aerosol container. Excellent and highly significantly bronchodilation was shown already 1 min post  inhalation, which further increased during testing time and with which results of subjective criteria for dyspnoeic changes correspond. The preparation may therefore be recommended for therapy of dyspnoeic attacks in an aerosol form equipped with metering valves.


[The influence of the broncholytic reproterol in persons with bradycardic arrhythmia upon impulse and conduction as well as irritability of the human ventricle (author's transl)]. The new  broncholytic 7-(3-[2-(3,5-dihydroxyphenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol, Bronchospasmin), a beta-phenylethyl-aminoalkyl-xanthine, was investiggated in two doses (60 and 90 mug i.v.) in patients who suffered from bradycardic arrhythmia. The influence on the primary and tertiary impulses and conduction in 36 cases and on the irritability of the human ventricle in 8 cases was tested. Reproterol led to a tolerable increase in the atrial and ventricular rate as well as to a desirable acceleration of the AV conduction. Irritability was significantly increased to a lesser degree than by the administration of orciprenaline and oxyfedrine. Except for a few, but not threatening, extrasystoles, two cases with bigeminal rhythms and some cases with a thermacogenesis, no undersible side effects were noted following injection.


[Ventilation and gas-dynamic work of breathing during CO2 stimulation in patients with airways obstruction prior to and following bronchodilation with reproterol (author's transl)]. A new, non-invasive method for measuring chemo-sensitivity of the respiratory center is described, one that may sensibly be applied in patients with airways obstruction. It is used for measurement of ventilation and gas-dynamic work of breathing in body plethysmography during a modified unsteady state of CO2 rebreathing technique. In 9 patients suffering from chronic obstructive bronchitis, a linear correlation between the end-expiratory CO2 partial pressure and the respiratory work rate vs. the airways resistance was established while between the end-expiratory PCO2 and the respiratory minute volume as well as the respiratory minute volume and the respiratory work rate vs. airways resistance, a non-linear correlation exists. In tests with 7-(3[2-(3 5-dihydroxyphenyl)-2-hydroxy-ethyl-amino]-propyl)-theophylline (reproterol, Bronchospasmin), a beta-phenylethyl-amino alkylxanthine, with known bronchodilating effects and a preparation for which pharmacological considerations of central-analeptic effects cannot definitely be excluded, this method revealed in patients with airways obstruction no breathing stimulation. In contrast, however, specific airways resistance in patients afflicted with bronchitis was statistically significantly reduced.


17beta-oestradiol and Enovid mammary tumorigenesis in C3H/HeJ female mice: counteraction by concurrent 2-bromo-alpha-ergocryptine. Chronic administration of 17beta-oestradiol (via drinking water) or the oral contraceptive Enovid (norethynodrel and mestranol) (0-1 mg injected s.c. twice weekly) to nulliparous C3H/HeJ female mice, beginning at one month of age and terminating at 20 months (17beta-oestradiol) or 22 months (Enovid), significantly increased the incidence of mammary tumours over solvent-treated controls. Concurrent treatment of the steroid-treated mice with 2-bromo-alpha-ergocryptine (CB-154) (0-1 mg s.c. injected daily) significantly reduced mammary tumour incidence and mammary hyperplastic nodule development to the control level. CB-154 is an efficacious inhibitor of pituitary prolactin secretion. These results demonstrate that steroid-induced mammary gland dysplasias can be sharply reduced by chronic CB-154 treatment, and suggest that some of the mammary tumorigenic activities of oestrogenic steroids in C3H mice are mediated via an increased secretion of pituitary prolactin.


Purification of L-glutamate decarboxylase by affinity chromatography. L-Glutamate decarboxylase (L-glutamate 1-carboxy-lyase, EC 4.1.1.15) from rat brain synaptosomal extract was partially purified by affinity chromatography. On further purification by DEAE-Sephadex A 50 and Sephadex G-200, L-glutamate decarboxylase was purified to greater extent. It was found that a single affinity chromatography by appropriate elution gave a highly purified protein giving a single band of high specific activity on polyacrylamide gradient gel slab electrophoresis with minimal contamination. Substrate specificity of the purified enzyme was modified in the presence of 6-azauracil or phenylalanine resulting in decreased specificity to L-glutamate and increased specificity to L-aspartate.


[State of the surface activity of pulmonary surfactant in rats at different periods after left-sided pneumonectomy]. The surface activity of the seven-fold washing of the right lung was measured on the modified Wilhelmy's balance after the leftside pneumonectomy in rats. It appeared to be normal (gamma min-23--24 dynes/cm) up to the 5th day, and at the remote postoperative periods. The intracellular edema of the air-blood barrier components and the release of the edema fluid into the alveolar lumen in the "vesicle" composition failed to influence the surface properties of the lung surfactant. A sharp increase of the alveolar dimensions on the 5th--7th postoperative day was followed by an increase of the surface-active properties of the lung washings (gamma-min-11--15 dynes/cm) and by the intensified secretion of the material of the osmiophilic lamellar bodies from the alveolar cells of the 2nd type into the alveolar lumen. The cytological mechanisms providing the intensified production of the surfactant in the hypertrophic alveoli are activation of the lipid synthesis in the alveolar cells of the 2nd type, their hypertrophy, and also the appearance of binuclear cells.


Antibody response to intravenous immunization following splenic tissue autotransplantation in Sprague-Dawley rats. The response to intravenous challenge with sheep erythrocytes was determined in Sprague-Dawley rats following autotransplantation of splenic tissue into the subcutaneous tissue, peritoneal cavity, or a surgically created omental pouch. There was a marked rise in heterophil antibody titer following intravenous challenge in ten control animals, and no rise in titer in nine of ten asplenic animals. Heterophil antibody titers increased in all of the animals with transplants, but the response in some was less than that in control animals. Thus autotransplanted splenic tissue demonstrated immunologic responses similar to those of normal, intact spleen.


Long-term treatment of acromegaly with bromocriptine. Seventy-three patients with active acromegaly were treated for three to 25 months with bromocriptine 10-60 mg/day. Seventy-one patients showed symptomatic and objective clinical improvement. This included reduction in excessive sweating, hand and foot size, and the number of headaches; improved facial appearance; and increased energy and libido. Abnormal visual fields became normal in two patients, one of whom had concomitant radiotherapy. Mean circulating growth hormone levels, obtained by averaging serial samples through the day, fell by more than 7 microng/l or became undetectable in 58 patients (79%) but did not reach normal values: only 15 patients had mean levels on treatment of 5 microng/l or less. Twenty-three patients were diabetic before treatment, and glucose tolerance became normal in 15 and improved in a further five. Provided the drug was started slowly side effects were minor when compared with the considerable clinical benefit obtained.


Teenage girls and venereal disease prophylaxis. One of the main aims of venereal disease education is to encourage the use of prophylactic techniques by sexually-active persons. To do this educators must convey information about prophylaxis that is relevant. This study was designed to assess the knowledge, attitude, and behaviour regarding prophylaxis of a group of 200 American adolescent girls. The findings suggest areas of prophylaxis that should be emphasised and ways that might encourage the acceptance and use of prophylactic measures. The study showed there were some misunderstandings and that it was important, for example to clarify the relationship of the oral contraceptive to possible venereal disease infection. Education involving both the cognitive and affective domains was indicated by the partial acceptance of the use of the condom, particularly by persons who had more than one partner.


Behavioural and social characteristics of the patient with repeated venereal disease and his effect on statistics on venereal diseases. The current study investigated personality characteristics and social circumstances in patients repeatedly infected with venereal diseases. An effort was made to identify characteristics that would differentiate a repeat patient (RP) from a non-repeat patient (NRP). Two studies were carried out. In the first, a group of patients from a venereal disease clinic in a large general hospital was first interviewed and then the patients were asked to complete a questionnaire. In the second study, an attempt was made to validate the findings from the first study by comparing data from RP and NRP venereal disease patients drawn from medical and social case histories from a second hospital. Results of both studies support the hypothesis that repeat patients are different from non-repeat venereal disease patients in terms of social and psychological characteristics. The significance of these findings is discussed.


A record system for contact tracing.

A record system for contact tracing. A system for recording information on patients and contacts was developed during a research project designed to measure the effectiveness of contact tracing. The record system has proved valuable in contact tracing, cross-referencing patients and their contacts, defining the characteristics of the patient and contact populations, and providing information for research and management. The value of a standardised system has been accepted by health workers who appreciate that its purpose is to increase efficiency and improve the care of infected persons. By October 1976 health workers in 16 clinics in the United Kingdom had started to use the system.


The hypertension detection and follow-up program: a progress report. The NHLBI-supported Hypertension Detection and Follow-Up Program (HDFP) is a community-based program designed to assess the value of early detection and vigorous treatment of persons with high blood pressure of varied severity. HDFP staff members have measured the blood pressures of 158,906 persons in their homes or work places in 14 communities across the United States. Of those persons, 10,940 were found to be hypertensive in a two-state screening process and were enrolled in the Program. Half were referred on a random basis to sources of care in the community, and half were invited to the special Stepped-Care clinics sponsored by the HDFP. These clinics, in a vigorous attempt to normalize blood pressure for all these hypertensive participants, stress intensive follow-up and special attention to achieve compliance with treatment. More than 80% under Stepped Care are continuing on therapy after 2 years, and three-fourths of these have achieved desired normal levels of pressure. The majority of hypertensives found in this Program have less severe elevations of blood pressure, and even among them reductions in blood pressure were substantial because of the vigorous follow-up and special attention to compliance. The HDFP is continuing its efforts to find to what extent sustained treatment of those with elevated blood pressure can reduce mortality or complications due to hypertension.


Bioavailability of two hydrochlorothiazide preparations. Eight healthy volunteers received hydro-chlorothiazide 75 mg as Dichlotride and Esiderx. Maximal plasma levels were significantly (p less than 0.05) higher after Dichlotride than Esidrex, 512 +- 189 and 376 +- 70ng/ml, respectively. However, the bioavailability of the two brands of hydrochlorothiazide did not differ significantly as judged by comparison of the AUC0 leads to 9h and AUC0 leads to chi, and the urinary recovery of hydrochlorothiazide during 48 hrs.


The infant food industry and international child health. Declining breast-feeding, with accompanying increased marasmus and diarrhea, has occurred in developing countries because of many factors, including inappropriate health services, new urban life styles, and so forth. The infant food industry must bear a considerable burden of blame as a result of "unethical" advertising. Responses have most recently included various journalistic and legal actions. There is a need for revised roles for the infant food industry, and for mechanisms to monitor intrinsically harmful practices.


[Concentrations in serum and tonsils after infection of azidocillin (author's transl)]. Prior to tonsillectomy 57 selected patients were given 1 g azidocillin i.v. in the form of a 10% aqueous solution. Serum samples were drawn at different times after the injection and both the serum and the tonsils were examined for azidocillin activity. The results of examination of 133 serum samples and 111 tonsils were evaluated, in addition to 74 paired values for tonsils and serum. Serum levels attained a maximum of 230 microng/ml and remained within measurable range for at least six hours. Tonsil levels  reached a maximum of 17 microng/g and after three hours began to drop below measurable range. The quotient for distribution between tonsils and serum rose during the first hour to 20-25% (average approx. 10%) and was about 3-6% three to four hours after injection.


Gas-liquid chromatographic determination of captan and two metabolites in milk and meat. A gas-liquid chromatographic (GLC) method has been developed for the determination of captan (N-trichloromethylthio-4-cyclohexene-1,2-dicarboximide) and 2 metabolites, tetra-hydrophthalimide (THPI) and tetrahydrophthalamic acid (THPMA), in milk and meat. The sample is extracted with ethyl acetate and is cleaned up by acetonitrile partition and silica gel chromatography where captan, THPI, and THPMA are separated. Captan is directly determined by GLC. THPI and THPMA are separately derivatized in an acetone solution of pentafluorobenzyl bromide. The resultant derivatives are purified separately on an Al2O3 column and quantitated by GLC, using an electron capture detector. Recoveries from milk samples fortified at 0.02-10 ppm ranged from 71 to 102%; recoveries from meat samples fortified at 0.04-10 ppm ranged from 75 to 99%.


A fluorescence detector for high-pressure liquid chromatography. We describe a fluorescence spectrophotometer adapted with a micro quartz flow cell to record the output of modern liquid chromatographs. The optical system is double beam in that the light source variations are cancelled out by a second photomultiplier, thus enhancing the sensitivity of the technique. The emission spectra may be scanned by stopping the flow in the chromatographic column and scanning the fluorescence detector. Many specific applications have been studied: polycyclic aromatic hydrocarbons, several vitamins, porphyrins, methyl anthranilate, etc. These are studied in natural samples and it is shown that the specificity of the fluorescence detector frequently obviates the need for sample preparation. The sensivitity available with the fluorescence detector for fluorescing compounds is often much greater than is available with variable-wavelength ultraviolet spectrophotometers. We report picogram-level detectability in real samples for many of the compounds that we have studied.


Splenic vein thrombosis in patients with a normal size spleen. The frequency of splenic vein obstruction secondary to pancreatic or retroperitoneal diseases has been only recently appreciated. The diagnosis is important because it frequently results in development of gastric and duodenal varices. It is often assumed that the diagnosis should only be suspected in patients with splenomegaly. This report describes 19 patients in whom splenic vein thrombosis was diagnosed by angiography although clinically unsuspected. In 11, the spleen was normal in size although extensive gastric varices were present. In 3 patients the presenting problem was massive hematemesis. Review of the upper gastrointestinal examinations in these patients showed thickened gastric or duodenal folds although in the absence of esophageal varices, the diagnosis was not made prior to angiography. More liberal use of angiography in patients with an appropriate clinical background, such as a history of pancreatitis, may lead to earlier and more frequent diagnosis of splenic vein obstruction. Varices that result from splenic vein obstruction can be cured by splenectomy.


Plasma thyroxine, 3,3',5-triiodothyronine and 3,3',5'-triiodothyronine during beta-adrenergic blockade in hyperthyroidism. Plasma thyroxine (T4), 3,3',5-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) were measured in 16 patients with Graves' disease. Patients were studied under the following conditions: first without any treatment, then, during beta-adrenergic blockade with propranolol, and finally after euthyroidism had been attained by carbimazole. During propranolol T3/T4 ratio decreased, whereas T4 remained unchanged. After carbimazole T3/T4 ratio returned to its pretreatment value. rT3/T4 ratio showed opposite changes. These results suggest that peripheral conversion of T4 into T3 and rT3 in hyperthyroidism is, at least partly, dependent on the functional status of the beta-adrenergic system. Suppressed peripheral conversion of T4 into T3 during beta-adrenergic blocking agents may contribute to the beneficial effects of these drugs in thyrotoxicosis.


The effect of prolactin on the lecithin content of fetal rabbit lung. 1 mg ovine prolactin was injected intramuscularly into rabbit fetuses (24th day of gestation) located in one of the two uterine horns exposed by laparotomy (n = 12). Fetuses in the other uterine horn were injected with an identical volume of vector and served as controls (n = 13). 2 days later the fetuses were removed by a second laparotomy and sacrificed. Analysis of lung tissue composition yielded the following results: (a) the prolactin-treated group of fetuses showed 40% higher total lung phospholipid content (17.0 +/- 0.8 micronmol/g) than the control group (12.2 +/- 0.5 micronmol/g); (b) the prolactin-treated group had a 67% higher lung lecithin content (8.7 +/- 0.8 micronmol/g) than the control group (5.2 +/- 0.4 micronmol/g); (c) dipalmitoyllecithin accounted for 67% of total lung lecithin in the prolactin-treated group and 44% in the control group. These differences were statistically highly significant (P less than 0.001). However, between the prolactin-treated and the control groups, there were no statistically significant differences in body weight and length, lung weight, the ratio of lung weight to body weight, DNA, protein and, water content. These results suggest that prolactin might be a trigger of lung surfactant synthesis in the rabbit fetus.


[Isolation and identification of some metabolites of mephenoxalone (Control-OM) from human urine (author's transl)]. Mephenoxalone (5-(o-methoxyphenoxymethyl)-2-oxazolidone) is degraded by various routes in the human, and some is excreted unchanged. In the metabolism of mephenoxalone, the phenoxymethyl ether bond is cleaved; thus o-methoxyphenol (metabolite I) was identified in urine, and 3-amino-1,2-propanediol (IIa) was found after alkaline hydrolysis. Hydroxylation of the benzene ring produces a phenolic hydroxymephenoxalone (metabolite III), and demethylation converts mephenoxalone into demethylmepheonxalone (metabolite IV). Opening of the oxazolidone ring leads to the production of 1-(o-methoxyphenoxy)-3-aminopropane-2-ol(metabolite V). Urine contains two further substances: 1-(o-hydroxyphenoxy)-3-aminopropene (metabolite VI) and dehydromephenoxalone (metabolite VII). Metabolite VI may be an artefact. Compounds III, IV and VII could only be detected after acid hydrolysis and enzymic cleavage with beta-glucuronidase/aryl sulphatase, whereas V and VI were detected only after acid hydrolysis. Thin layer chromatography revealed three further metabolites, which were not identified.


Gonadal dysgenesis with Graves's disease. Hashimoto's thyroiditis has previously been associated with gonadal dysgenesis. Recent evidence suggests that Graves's disease and Hashimoto's thyroiditis are disorders of cell-mediated immunity and may have a common genetic predisposition. However, patients with both Graves's disease and the Turner syndrome have been reported only rarely. Three such cases are presented and the relation among gonadal dysgenesis, Hashimoto's thyroiditis, and Graves's disease is discussed.


RDS and tracheal phospholipid composition in twins: independent of gestational age. The surfactant phospholipids in the tracheal effluent of eight pairs of preterm twins were followed, serially. In four pairs only one of the twins had RDS; in the other four pairs both twins had RDS. Twins with and without RDS had markedly different surfactant phospholipids. Phosphatidylglycerol was absent in all twins with RDS. L/S ratios in tracheal effluent increased after birth in infants with and without RDS. With recovery from RDS, phosphatidylinositol increased. The study helps confirm previous studies of the necessity of the acidic phospholipids, PI and PG, in stabilizing lecithin, as well as that surfactant composition can be independent of gestational age.


Urine solute excretion in growing low-birth-weight infants. Fifteen thriving low-birth-weight infants who weighed less than 1,950 gm at birth were randomly selected to study the urine solute excretion on two milk-based proprietary formulas, SMA or Formula 4. The results showed that urine oxmolality rose progressively with increasing caloric concentration and was 78, 111, and 163 mOsm/kg H2O on 67, 80, and 100 kCal/dl SMA, respectively. Formula 4 gave rise to significantly higher urine osmolality (133 mOsm/kg H2O) than SMA, when fed at the same caloric density of 67 kCal/dl. Although the dependence of urine solute excretion on dietary load was confirmed, the rapidly growing low-birth-weight infant appears to incorporate a larger portion of potential urine solute into growing tissues, than is the case in the term infant.


Comparative bioavaiability of four commercial quinidine sulfate tablets. A comparative bioavailability study was performed using four commercially available, chemically equivalent brands of quinidine sulfate tablets. Two 200-mg tablets were administered to 11 different subjects following a completely randomized crossover design. Serum levels, urinary excretion data, and derived pharmacokinetic parameters were compared statistically. There were no statistical differences in the extent of quinidine absorption from the four brands of tablets as evidenced by the cumulative urinary excretion values and the areas under the serum level-time curves. Significant differences in the mean serum levels at 0.5 and 1 hr and differences in the peak times and absorption rate constants indicate that there was a difference in the absorption rate between Treatments A and D and C and D. A significant difference in the peak times also was noted for Treatments B and C. When mean disintegration times for the four tablet formulations were compared with their values for ka, tmax and mean serum levels at 0.5 and 1 hr, rank-order correlations were observed. A considerable degree of variability in quinidine elimination was noted, with half-life values ranging from 2.71 to 8.12 hr (mean half-life of 5.36 hr).


Endoscopic electrosurgical papillotomy and manometry in biliary tract disease. Endoscopic papillotomy was performed in 13 patients after cholecystectomy for retained or recurrent common bile duct calculi (11 patients) and a clinical picture suggesting papillary stenosis (two patients). Following endoscopic papillotomy, ten of the 11 patients spontaneously passed common bile duct (CBD) stones verified on repeated endoscopic retrograde cholangiopancreatography (ERCP) study. One patient failed to pass a large CBD calculus; one patient experienced cholangitis three months after in inadequate papillotomy and required operative intervention. Endoscopic papillotomy substantially decreased the pressure gradient existing between the CBD and the duodenum in all five patients studied with ERCP manometry. Endoscopic papillotomy is a relatively safe and effective procedure for postcholecystectomy patients with retained or recurrent CBD stones. The majority of CBD stones will pass spontaneously if the papillotomy is adequate.


Diethylstilbestrol: recommended dosages for different categories of breast cancer patients. Report of the Cooperative Breast Cancer Group. A total of 523 postmenopausal breast cancer patients with progressive disease were entered in a radomized, double-blind study of four dosages of diethylstibestrol (DES): 1.5, 15, 150, OR 1,500 MG/DAY. Higher dosages produced significantly (p less than .05) higher regression rates: 21% for the 1,500 mg dosage, 17% for the 150 mg dosage, 15% for the 15 mg dosage, and 10% for 1.5 mg dosage. Durations of regressions were similar regardless of the dosages used to induce them. Although the highest dosage produced the highest regression rate overall, selecting the best dosage or treatment of choice for each type of patient based on menopausal age and on dominant metastatic site would result in more regressions.


Compassion vs control. Conceptual and practical pitfalls in the broadened definition of child abuse. A broadened understanding of child abuse has enabled practitioners to think of the parents of abused children not as evil murderers but as human beings caught in a complex web of social isolation and deprivation. Concomitantly, child abuse laws have changed dramatically in the last decade to include virtually all childhood physical symptoms of family crisis; physical, sexual, and emotional abuse and child neglect are now reportable by nearly all professionals who have contact with children. There has been a dramatic increase in case reports, but the services for which families become eligible do not approach the humane rhetoric and intent of child abuse legislation. Society and the helping professions are caught in a dilemma that we characterize and address clinically as compassion vs control.


Radiation exposure and thyroid cancer.

Radiation exposure and thyroid cancer. There are abundant experimental and clinical data to associate radiation exposure and thyroid cancer. The incidence of thyroid cancer increases with increasing doses of thyroidal radiation from 6.5 rads to 1,500 rads, but higher doses tend to destroy the gland and are associated with hypothyroidism rather than cancer. The peak occurrence of thyroid tumors is between five and 30 years after exposure, but a person may develop thyroid tumors as long as 50 years after irradiation. Multiple thyroidal lesions or disorders, including adenomas, thyroditis, and hypothyroidism as well as malignant neoplasms, can occur after radiation exposure. It is imperative, therefore, to study carefully all patients with a history of radiation exposure to the gland and to observe them carefully for life. Suggestions are made for the management of thyroid disease in these patients.


Infection and pheochromocytoma.

Infection and pheochromocytoma. A urinary tract infection with possible septicemia and endocarditis developed in a 36-year-old man. The illness was complicated by pulmonary embolism, thrombocytopenia, hematemesis, hepatic dysfunction, paralytic ileus and accelerated hypertension. The latter finding suggested pheochromocytoma. Treatment with antibiotics and phenoxybenzamine hydrochloride was associated with notable clinical improvement. A chromaffin cell tumor was surgically removed above the lift kidney. Conclusively, a pheochromocytoma may mimic and be present in association with infection.


Parotid carcinoma and posterior fossa schwannoma following irradiation. Report of a patient treated in infancy for benign ear disease. A 23-year-old man had received irradiation for a benign ear problem at the age of 1 year. Twenty year later, a malignant left parotid carcinoma and a right jugular foramen schwannoma developed. Earlier reports in the literature suggest that radiation can induce tumors in the head and neck. The localization of both tumors and the histological features of the parotid tumor suggest that they were radiation-induced.


Clinically suspected deep venous thrombosis of the lower extremities. A comparison of venography, impedance plethysmography, and radiolabeled fibrinogen. To define the utility of new diagnostic approaches in patients with clinically suspected deep venous thrombosis of the lower extremities, 42 legs of 33 patients were studied by fibrinogen labeled with radioactivie iodine (125I) impedance plethysmography (IPG), and contrast venography. The clinical diagnosis was confirmed in approximately two thirds of the legs and patients. In venogram-positive legs, fibrinogen 125I was positive in 70%, IPG in 61%, and one of the two in 78%. In venogram-negative legs, fibrinogen 125I was positive in four (21%) and IPG was negative in all. It was found that the size, age, and location of the thrombus, collateral vein development, heparin sodium therapy, and technical-interpretive choices can influence both IPG and fibrinogen 125I results. The data demonstrate that the fibrinogen 125I and IPG procedures can assist physicians in the diagnosis of clinically suspected deep venous thrombosis of the lower extremities.


Benign breast disease and oral contraceptive use. A random selection of 1,230 upstate New York childbearing women was used to examine the history of oral contraceptive use in women with a clinical diagnosis of benign breast disease. We found that 73 women who had benign breast disease had a reduced duration of pill use. When determining the reason for this reduction, we found that in a significant portion (P less than .05) of our benign breast disease cases, the women had been advised by their physicians to discontinue pill use for breast-related reasons. We then surveyed a large group of upstate New York physicians. One third of them considered benign breast disease a potential contraindication for starting oral contraceptive use. Nearly one half throught the development of benign breast disease to be a potential contraindication for continuing oral contraceptive use. It is premature to conclude that oral contraceptive usage protects against benign breast disease.


A cooperative study of hospital frequency and character of transient ischemic attacks. II. Performance of angiography among six centers. Angiographic procedures were carried out on 36% of 1,328 patients suspected of having transient ischemic attacks (TIA). Among six participating centers, this ranged from 13% to 82%. This large difference might be related to the number of patients considered good surgical candidates and differences in the use of screening noninvasive diagnostic techniques. Arch studies, using catheter techniques, were performed most often. Although 13% of the patients had transient complications, permanent neurological deficits occurred in only 0.65%. Angiographic lesions were best correlated to clinical symptoms in those patients thought to definitely have carotid artery system TIA but were commonly seen in all other groups. Thus, clinical correlation was poor.


Myositis ossificans traumatica. Association with hemophilia (factor XI deficiency) in a football player. A case report of an outstanding college football halfback with partial factor XI deficiency, recurrent ecchymosis, and myositis ossificans is reviewed. The association of multiple areas of myositis ossificans and partial clotting-factor deficiency has not been noted in the past. The importance of considering this diagnosis in participants in contact sports with the above findings is emphasized.


St Louis encephalitis. The 1975 epidemic in Mississippi. In 1975, 229 laboratory-documented cases of St Louis encephalitis, 36 of which resulted in death, occurred in Mississippi. A total of 58% of these persons had encephalitis, 15% had aseptic meningitis, 21% had a febrile illness with no known CNS involvement, and 6% had other syndromes. Attack rates and case-fatality ratios increased with age. Although 60% of the cases occurred in a four-county area of northwest Mississippi, cases occurred in 42 of the 82 counties throughout the state. The epidemic erupted almost simultaneously, with variable intensity, in widely separated areas. Mosquito-control, measures were applied, but the results were not quantified.


Mucocutaneous lymph node syndrome. A case masquerading as Rocky Mountain spotted fever. Mucocutaneous lymph node syndrome is a recently described entity whose principal signs and symptoms include fever, unresponsiveness to antibiotics, congested conjunctivae, reddening of the oral cavity, lips, palms, and soles, exanthem, edema, nonsuppurative cervical adenitis, and desquamation of the fingertips. Almost 7,000 cases have been reported in Japan. Analysis of the 39 cases reported in the United States reveals findings similar to those in Japan. United States cases, however, have had a higher boy-to-girl ratio (2:1), and age distribution peaks at a later time (3 years of age). We report a case with many characteristics of Rocky Mountain spotted fever, including a positive Well-Felix reaction. Some cases of mucocutaneous lymph node syndrome may be misdiagnosed as Rocky Mountain spotted fever.


Airborne contamination of fine-particle nebulizers. To determine whether bacteria present in ambient air play a role in the contamination of fine-particle reservoir nebulizers, nebulizers were placed in operation in separate hospital locations having qualitatively and quantitatively different bacterial flora in background air. Nebulizers placed in a surgical intensive care unit that had higher numbers of bacteria and a predominance of Gram-negative organisms in background air had a significantly higher incidence of nebulizer contamination (33.0%) than did nebulizers placed in a non-patient-care area that had lower bacterial counts and a predominance of Gram-positive organisms (0%) (P less than .05). The present study indicates that airborne contamination of fine-particle reservoir nebulizers occurs when bacteria present in ambient air enter the nebulizer during its operation.


Blood pressure studies in 14 communities. A two-stage screen for hypertension. the Hypertension Detection and Follow-up Program (HDFP) is a community-based national trial to determine whether special programs can improve the treatment for persons with uncontrolled hypertension and reduce morbidity and mortality in wide strata of these patients. A total of 158,906 persons, aged 30 to 69 years, were screened to identify those with a diastolic blood pressure (DBP) of 95 mm Hg or higher. Age-sex-race means and distributions of DBP at a first and a second screen and prevalence rates or actual hypertension by sex, race, and level of control suggest a recently increased awareness of hypertension with more widespread and effective treatment, especially among women, although blacks under treatment had their DBP controlled less frequently. The response to this program of screening and initial follow-up offers encouragement for improved community control of high blood pressure.


Chemotherapy for bronchogenic carcinoma. Methotrexate, doxorubicin, cyclophosphamide, and lomustine. A combination chemotherapy (MACC) consisting of methotrexate, doxorubicin hydrochloride (Adriamycin), cyclophosphamide, and lomustine (CCNU) was given to 41 patients with stage III bronchogenic carcinoma, 34 of whom had disseminated disease. The objective response rate was 46% for all patients with a median actuarial survival of nine months. Response was seen in all cell types, including four of ten patients with squamous cell carcinoma, six of 17 with adenocarcinoma, and six of seven with small-cell anaplastic carcinoma. Prolongation of survival was apparent for patients of all cell types. Toxic reactions were moderate and allowed for easy outpatient use.


Medical interpreting for hearing-impaired patients. Medical interpreting for deaf patients is a new dimension of the medical field. Medical interpreting allows for the fast, accurate, and complete exchange of medical information between medical professionals and their deaf patients. The exchange of accurate medical information is critical to the early diagnosis and treatment of medical problems.


Genetic damage from diagnostic radiation. Using the data from the Tri-State Leukemia Survey and a mathematical model, the hypothesis that low levels of diagnostic radiation produce severe genetic damage that is expressed in the child of the exposed person as leukemia and other diseases is tested. It is estimated that for about 1% of the exposed persons who are affected by radiation, there is a 50-fold increase in the risk of leukemia and a five-fold increase in certain other diseases.


Hemolytic anemia in Wilson's disease. A report of three cases with transient increase in hemoglobin A2. Three patients with Wilson's disease and initial manifestations of intravascular hemolysis also had transient elevations of hemoglobin A2. It is important to recognize such manifestations in establishing an early diagnosis.


Treating acute acetaminophen poisoning with acetylcysteine. A patient ingested 15.6 gm acetaminophen and sought medical attention after seven hours. At that time, her plasma acetaminophen level was 217 microng/ml. Treatment with acetylcysteine was begun eight hours after the ingestion. The clinical course of this patient was characterized by a mild illness with a minor elevation of liver enzyme values. A number of factors predicted severe hepatotoxicity for this patient had she not received treatment.


Oral contraceptives and blood pressure.

Oral contraceptives and blood pressure. Both cross-sectional and longitudinal analysis of data from 13,358 women showed that oral contraceptive use is associated with a slight but statistically significant (P lesser than .05) rise in mean blood pressure, which is reversible. The age-adjusted proportion of oral contraceptive users with a blood pressure over 140/90 mm Hg was about three times that on nonusers. These findings are caused by a uniform upward shift in the blood pressure distribution of oral contraceptive users compared to nonusers. Women continuing oral contraceptive use had no appreciably greater change in blood pressure between two visits than persistent nonusers. The clinical implications of a mild contraceptive-induced blood pressure elevation (systolic, 5 to 6 mm Hg; diastolic, 1 to 2 mm Hg) remain unsettled but disturbing.


Distribution pattern of metastatic bone disease. A need for total body skeletal image. Distribution patterns of metastatic bone disease in 62 patients with soft-tissue cancers showed that 60% of bone lesions were located in the axial and 40% in the appendicular skeleton. Thirteen percent of the lesions were in appendicular regions not usually included in routine imaging studies. The majority of the metastatic skeletal lesions were clinically asymptomatic. The serum alkaline phosphatase level is a poor indicator of early bone metastases.


Mikulicz disease and subsequent lupus erythematosus development. In a 12-year-old boy with clinical and histologic features of Mikulicz disease, systemic lupus erythematosus (SLE) developed two years later. Atrophic plaques and nodules in the skin along with substantial increase in salivary gland enlargement characterized the onset of SLE. There was lack of renal and joint manifestations, and no evidence of keratoconjunctivitis sicca or xerostomia was seen. Histopathologic changes in the skin lesions included mucinous infiltrates, chronic vasculitis, and dermal-epidermal junction findings typical of SLE. Direct immunofluorescene studies of skin lesions and normal-appearing skin showed granular deposition of immunoglobulins and complement at the dermal-epidermal junction zone. Level of anti-DNA antibodies was noticeably elevated, and the serum C3 value was depressed. The patient's response to systemic corticosteroid therapy was dramatic.


Shock lung with massive tracheal loss of plasma. Fulminant pulmonary edema developed in two young, healthy adults within one hour after blood loss, hypolemic shock, and an anaphylactoid reaction to intravenous pyelogram dye. Pulmonary edema developed and they subsequently passed large amounts of edema fluid through the endotracheal tube. Massive loss of plasma-like fluid from the lung required frequent evacuation of the endotracheal tube and intravenous replacement with large amounts of albumin-containing fluids. Both patients were treated with a volume respirator, positive end-expiratory pressure, 100% oxygen, corticosteroids, and tracheostomy. Both patients recovered from massive pulmonary edema with very severe hypoxemia and, three months afterwards, had normal pulmonary function, blood gas levels, and no evidence of pulmonary injury.


Comparison of the productivity of women and men physicians. Data obtained from random samples of 87 women and 95 men physicians in the Detroit metropolitan area indicate that, at the time of surgery, 84% of the women and 96% of the men were engaged in medical work. Only 7% of the women were not working because of reasons related to the traditional female role. Fifty-nine percent of the women and 87% of the men had worked full-time since medical school graduation. Fifty-one percent of the women, compared to 39% of the men were in primary care specialties. Since medical graduation, women physicians spent 90% as much time in medical work as did the men, despite the fact that most of the women had full responsibility for homes and families.


Venereal warts vs Bowen disease. A histologic and ultrastructural study of five cases. Verrucous growths of the genitalia in young patients are usually condylomata acuminata. In five cases this type of genital lesion, viewed by light microscopy, showed dysplastic cellular changes of Bowen disease, a diagnosis that was further confirmed by electron microscopy. Bowen disease should be included in the differential diagnosis of verrucous lesions of genitalia in young people and should be ruled out by histologic examination.


Stylet injury syndrome.

Stylet injury syndrome. Failure to properly use the stylet when withdrawing a spinal puncture needle may cause aspiration of a lumbar nerve root and adjacent arachnoid, thereby fixing the nerve in the epidural space. Root fixation may cause a painful syndrome, requiring laminectomy and replacement of the nerve root within the subarachnoid space. Since laminectomy is rarely performed at the lumbar puncture site, the frequency of the syndrome remains undetermined.


Overwork.

Overwork. Overwork, ie, working beyond one's endurance and recuperative capacities, may be a hazard in certain personality types engaged in open-ended occupations. Some persons appear to lack an inner "governor" and for various reasons ignore the commonplace signs that inform one of the need for rest or recreation. If they are engaged in occupations that do not have a finite workday, they may at times exceed their bodies' ability to recover. Clusters of symptoms may then develop, some of which may mimic serious physical ailments. Treatment depends on diagnosing the extent of illness and eliciting the underlying causes. Correction involves enforced rest, therapy that may vary from counseling to hospitalization and specialized treatment, but that must include the reeducation of the person to be aware of and make provision for his physical and emotional needs.


Association between oral contraceptives and myocardial infarction. A review. Analysis of the association between oral contraceptive use and the development of myocardial infarction in women less than 50 years of age shows that cigarette smoking is the most important factor in increasing the likelihood of myocardial infarction. This effect is independent of oral contraceptive use but oral contraceptive use also appears to be a risk factor; however, their use in the absence of other predisposing factors appears to have only a small effect on increasing the risk of dying from myocardial infarction. This small increase is of the same order of magnitude as the increased risk of death from thromboembolic disease. Oral contraceptive users more than 30 years of age who have other factors that increase the likelihood of myocardial infarction appear to have a substantially higher death rate.


Benign transient eosinophilia following intravenous urography. Eosinophilia, a component of the allergic response, may occur after the use of iodinated radiographic contrast media for intravenous urography. A benign transient elevation in differential eosinophil count was seen in 21 of 101 patients following the injection of iodinated contrast agents for that purpose.


Intoxication caused by interaction of chloramphenicol and phenytoin. A patient with a brain tumor and seizures who was receiving maintenance doses of phenytoin was given chloramphenicol on three occasions. Her neurological status was both complicated and obscured by the reoccurrence of phenytoin intoxication. Retrospective drug analysis showed a marked elevation of serum concentrations of phenytoin during each course of chloramphenicol.


The lymphographic findings in a case of lymphocytic lymphoma presenting as recurrent chylothorax. A case of lymphocytic lymphoma is presented. The unusual mode of presentation as a result of bilateral chylothoraz is described. The value of lymphography in establishing the site of lymph leakage and in the establishment of the underlying diagnosis is demonstrated and discussed.


Biological significance of piezoelectricity in relation to acupuncture, Hatha Yoga, osteopathic medicine and action of air ions. Piezoelectric properties of biological macromolecules such as proteins, nucleic acids and mucopolysaccharides are reviewed in this paper. It is indicated that the structural elements of the human body composed of these piezoelectric substances are capable of transducing a mechanical energy into an electric current. Such a transduction may be brought about by movements of an acupuncture needle, osteopathic manipulations; Hatha Yoga postures or action of negatively charged air irons. It is postulated that electric current induced by stimulation of the specific sites on the surface of human body flows towards the internal organs along the semiconductive channels of biologic macromolecules. Electric current induced either by the piezoelectric transduction or directly applied from an external source may in turn stimulate individual cells in the target organ. Involvement of electrical phenomena in regulatory mechanisms on cellular and molecular levels is discussed.


Decline of stomach cancer mortality rates in a high-risk geographical area. An investigation on gastric cancer death rates per 100,000 population, by sex and age groups in Chile, covering a 34-year period (1941-1974), was made. The yearly change in gastric cancer mortality rates, calculated by linear regression analysis, for males 25-34 years of age (-0.043), P less than 0.00005), 35-44 (-0.381, P less than 0.00005), 45-54 (-1.340, P less than 0.00005), 55-64 (-2.080, P less than 0.00005), 65-74 (-0.602, N.S.), and age-adjusted death rates for persons aged 25-74 years (-0.959, P less than 0.0006) showed negative regression coefficients. The yearly change in gastric cancer death rates for females 25-34 years of age (-0.051, P less than 0.00005), 35-44 (-0.468, P less than 0.00005), 45-54 (-1.430, P less than 0.00005), 55-64 (-2.978 P less than 0.00005), 65-74 (-1.841, P less than 0.00005), and age-adjusted rates for persons aged 25-74 years (-0.991, P less than 0.00005) also exhibited negative regression coefficients, all being statistically highly significant.


Value of simultaneous T3, T4, and TSH measurements for management of graves' disease in children. One hundred simultaneous determinations of serum T4 and T3 were performed during the course of treatment of 23 children and adolescents with Graves' disease. Five patients were previously untreated and six were experiencing relapse after treatment was discontinued. During relapse, increased T3 concentration is frequently present when serum T4 concentration is normal and T3 measurement is therefore more reliable for early detection of relapse. During therapy with thionamides, T4 measurement alone is often misleading in assessing adequacy of control achieved by therapy. Commonly, patients who clinically have hyperthyroidism have serum T4 concentrations within the normal range but continue to have elevated T3 concentrations (T3 toxicosis). Similarly, T4 can be suppressed into the hypothyroid range in the clinically euthyroid patient with either a normal or high T3 concentration. In these patients, determination of serum T3 often prevents premature reduction of thionamide dosage. When T4 and T3 concentrations do not clearly demonstrate presence or absence of hypothyroidism, measurement of serum thyroid stimulating hormone can be of value.


Pachyonychia congenita (Jadassohn-Lewandowski syndrome: case report. We report an illustrative case of pachyonychia congenita, with a description of the presenting complaints, the associated physical findings, the rationale for surgical treatment, and the technical aspects of the surgical treatment.


Malabsorption in relation to abdominal irradiation and quadruple chemotherapy for lymphosarcoma. A case of severe diarrhoea and steatorrhoea following chemotherapy and abdominal irradiation for lymphosarcoma, is described. Investigations demonstrated bile acid malabsorption, and treatment with cholesytramine and a low fat diet was successful. A questionnaire was sent to thirty-two subjects who had undergone similar treatment for similar pathology and failed to demonstrate any sustained alteration of bowel function. Additionally, nine of these subjects underwent a 14C-glycocholic acid test and no evidence of interruption of the enterohepatic circulation of bile acids was found.


The pathogenesis of peripheral aneurysms of the central nervous system: a subject review from the AFIP. Most central nervous system aneurysms occur around the circle of Willis, and are congenital or arteriosclerotic in origin when in that location. Peripherally located aneurysms are either idiopathic or secondary to infection, tumor embolus (from choriocarcinoma and cardiac myxoma), Moyamoya disease, or trauma. The pathophysiologic features of these aneurysms are discussed.


[Correlation between gastrointestinal absorption and uptake of radioisotopes by the critical organs]. This study was undertaken to investigate the correlation between gastrointestinal absorption of radioisotopes and uptake by the critical organ during the same period using 85Sr, 109Cd, 131I and 203Hg as radioisotopes. When the distribution of 85Sr, 109Cd, 131I and 203Hg in mice were investigated by means of the whole body autoradiography, these critical organs were determined as follows; 85Sr: bone, 109Cd: liver, 131I: thyroid gland and 230Hg: kidney. When the correlation between the injected dose and the uptake dose by the critical organ of 85Sr, 109Cd, 131I and 203Hg were investigated, uptake dose the critical organ expressed as cpm per gram of organ was in direct proportion to the injected dose and that expressed as % of the injected dose per gram of organ was held constand in either case. When the coefficient of correlation between gastrointestinal absorption and uptake by the critical organ of 85Sr, 109Cd, 131I and 203Hg were calculated, a positive correlation was revealed in either case. It is concluded from the results obtained that in vivo or in situ method, gastrointestinal absorption of radioisotopes received a support from uptake by the critical organ during the same period.


[Study of distribution of 169Yb, 69Ga and 111In in tumor tissues by macroautoradiography; comparison between viable and necrotic tumor tissues]. The localization of 169Yb, 67Ga and 111In in tumor tissues was determined macroautoradiographically. 169Yb-citrate and 111In-citrate were injected intravenously to the rats subcutaneously transplanted Yoshida sarcoma and were injected intraperitoneally to the mice subcutaneously transplanted Ehrlich tumor. These animals were sacrificed 3, 24 and 48 hours after injection. These tumor tissues were frozen in n-hexane (-70 degrees C) cooled with dry ice-acetone. After this, these frozen tumor tissues were cut into serial thin sections (10 micron) in the cryostat (-20 degrees C). One of the slice of these sections was then placed on X-ray film and this film was developed after exposure of several days. On the other hand, next slice of these sections were then stained using the hematoxylin and eosin. From the observations of these autoradiogram and H-E stained slice, the following results were obtained. Concentration of 169Yb, 67Ga and 111In was predominant in viable tumor tissue rather than in necrotic tumor tissue, regardless of time after the administration. 67Ga and 111In were distributed uniformly in viable tumor tissue, but deposition of 169Yb was observed more avidly in viabl tumor tissue neighboring to necrotic tumor.


[Human proinsulin-C-peptide radioimmunoassay method; stability of the assay kit]. We have been studies time sequent stability each on standard human-C-peptide, human-C-peptide antiserum, 125I-tyrosyl human-C-peptide and the assay kit (all reagent) which is necessary in human proinsulin-C-peptide radioimmunoassay(RIA). Also we measured using this assay system, human proinsulin C-peptide in blood after oral administration of glucose to normal subject. Standard human-C-peptide and human-C-peptide antiserum were very stable on storage at 4 degrees C, 125I-tyrosyl human-C-peptide was unstable as compared with the former two, The stability of the assay kit was influenced by the stability of 125I-tyrosyl human-C-peptide, and was stable at 4 degrees C for ten weeks after preparation. Three lots of the assay kit prepared at different period showed almost same stability. We think this assay system using the assay kit is satisfactory in respect of stability. The measured values of human proinsulin-C-peptide in blood, using this assay system, showed insulin secretory reaction after oral administration of glucose.


[Trial preparation and evaluation of a 81mKr-generator for medical use]. A prototype 81mKr-generator consisting of an ion exchange column and some attachments for handling was prepared on trial. Parent nuclide 81Rb obtained by the reaction of 82Kr(p, 2n)81Rb was absorbed on the resin, and radionuclidic purity, sterility and apyrogenicity of the generator eluate were examined. Analysis of gamma-ray spectrum obtained with a Ge(Li) detector and a multichannel pulse height analyzer revealed that the nuclidic purity of the 81mKr in the eluate was 99.997-99.999% with 0.001-0.003% of 79Kr at the start of the elution. Sterility and apyrogenicity of the eluate were proved by J.P. sterility test and limulus test respectively. All results obtained show that the 81mKr-generator is very suitable for medical application.


[Tumor affinity of 99mTc-labeled radiopharmaceuticals, 99mTc-Sn-urokinase and 99mTc-Sn-mannitol]. Biolgic distribution of 99mTc-labeled fibrinolytic agent, urokinase, and 99mTc-labeled mannitol, which was obtained as a side-product in the preparation of 99mTc(Sn)-urokinase, have been studied in Ehrlich's tumor-bearing mice to get a promising indicator for the positive delineation of malignant tumor. The preparation of 99mTc-labeled radiopharmaceuticals, 99mTc-UK and 99mTc-Man, was made by the reduction with stannous chloride and labeling efficiency was examined by Sephadex G-25M gel chromatography and by silica gel plate thin layer chromatography. Labeling yield of 99mTc-UK by Sephadex G25M in 0.9% NaCl eluant was 13% and that of 99mTc-Man by TLC in 85% methanol solvent was over 95%. A higher uptake to the implanted solid tumor tissue in mice was found in 99mTc-Man than in 99mTc-UK, of which the excellent tumor accumulation was expected from the positive delineation of malignant tumor with 131I-fibrinogen, 131I-fibrinogen antibody and 125I-plasmin. The poor result in 99mTc-UK, however, may be attributed to the poor fibrinolytic activity of Ehrlich's tumor. In biologic distribution of 99mTc-UK was found high concentration for liver kidney and stomach. In the other hand, a higher tumor tissue uptake, a fast blood disappearance and a low concentration for different organs were found in biologic distribution of 99mTc-Man. Therefore, 99mTc-Man may be assumed as a more preferable 99mTc-labeled tumor localizing radiopharmaceuticals, to which it would be needed as absolute biologic characteristics that 99mTc-labeled compounds possess a high tumor uptake as well as a fast blood disappearance with a low uptake for different organs. However, the possible delineation with 99mTc-labeled fibrinolytic agents, including urokinase and streptokinase, may be promised for malignant tumors in human-subject, which generally have a higher activity in fibrinogenesis than in fibrinolysis.


[Remote system for the mass production of short-lived radioisotopes in a cyclotron. Development of the system and radioisotope production]. A system was developed for producing short-lived radioactive substances (11CO, 11CO2, 13NN,  13NH3, 18F-, 62Zn2+, 123I-, etc.) on a scale enough for clinical use, which could also be used for analyzing them rapidly and for investigating their production methods, with less received dose by workers. The system enabled us to produce remotely several tens mCi of of short-lived radioactive susbtances readily usable for clinical diagnosis, continuosly for radioactive gases, 11CO, 11CO2 and 13NN, or repeatedly at short intervals for radioactive aqueous solutions of 13NH3, 18F-, etc. Employing this system, the average received dose per month was reduced considerably.


[Production of 123I by alpha and 3He irradiation of natural tellurium]. In order to determine the optimum irradiation condition to produce 123I for nuclear medical use, excitation curves and thick-target yield curves were measured by means of stacked foil technique for alpha and 3He reactions producing 123Xe, 123I, 125Xe and 130I, both from natural tellurium. The 123Xe yields from natural tellurium are too low for routine production. However, by bombarding 76.5% isotopically enriched 123Te target with 30MeV 3He particles, 724 micronCi/micronAh of 123I would be obtained, whereas the level of 125I contaminat would be about 0.14%. 130Te contaminant in enriched 123Te target produces 130I alpha and 3He bombardment, although it has not been reported in the past. The 130I contaminant can be easily eliminated.


[Human proinsulin. C-peptide radioimmunoassay method. 125I labeling of human proinsulin. C-petide]. 125I-labelled human-C-peptide was prepared by chloramin T method, enzymic method and active ester method, respectively. Using respective 125I-labelled human-C-peptides in human proinsulin-C-peptide RIA, we compared the binding (Bo/T%) to antibody, displacement by standard human-C-peptide, the recovery test and stability. The usable 125I-labelled antigen for human proinsulin-C-peptide RIA could be prepared by chloramin T method and enzymic method wich labelled 125I to tyrosyl human proinsulin connecting peptide, and active ester method which conjugates 125I-labelled active ester to human proinsulin connecting peptide. The differences among those 125I-labelled antigens was not observed in displacement (B/Bo%) by standard human-C-peptide and the recovery test. In the case of constant preparation of 125I-labelled antigen for RIA, the enzymic method was the best from the viewpoint the reaction ratio is stable and stability of Bo/T% is good.


The effect of route of administration on the anthelmintic efficacy of benzimidazole anthelmintics in sheep infected with strains of Haemonchus contortus and Trichostrongylus colubriformis resistant or susceptible to thiabendazole. Observations of erratic anthelmintic activity of fenbendazole against known standardised thiabendazole-resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep were investigated. Fenbendazole at a dose rate of 10 mg/kg body weight was administered by oral, intra-ruminal or intra-abomasal routes, and was most effective against both resistant strains following intra-ruminal administration. In addition thiabendazole, oxibendazole, fenbendazole, parbendazole and mebendazole plus two unrelated compounds, levamisole and morantel tartrate, were used at one and a half times their suggested or recommended therapeutic dose rate against thiabendazole-resistant strains of H contortus and T colubriformis in sheep; each drug being administered by the intra-ruminal or intra-abomasal routes. Fenbendazole was more effective against both strains following intra-ruminal administration. Parbendazole was more effective against the resistant strain of T colubriformis following intra-ruminal administration. At the dose rate chosen for the other benzimidazoles used against these resistant strains, there was no difference in anthelmintic efficacy due to route of administration. Levamisole was highly effective against both resistant strains, irrespective of the route of administration. In the groups treated with morantel tartrate, the results obtained were difficult to interpret due to mortalities and a highly variable response in the surviving sheep. Fenbendazole, thiabendazole and mebendazole when used at their suggested or recommended therapeutic dose rate in sheep, were highly effective against known thiabendazole-susceptible strains of H contortus and T colubriformis following both intra-ruminal or intra-abomasal administration.


[Ventilation mechanics in the newborn. II. Dynamical measurements of the isolated lungs (author's transl)]. On 31 pairs of lungs from still borns and newborns and new borns of differing stages of maturation and age (23rd week of gestation up to the 24th week after birth), dynamical measurements within an artificial thorax were performed including systematical changes of ventilation types, particularly breathing frequency. In 12 pairs of lungs, surfactant activity was diminished. In these cases, a marked heterogeneity of ventilation and partly excessive increases of work of breathing correlated with the life span following birth could be shown, and some pathogenetical ways of cardiorespiratory failure as well as mechanisms of damaging late effects of the lungs following respiratory distress syndrome could be demonstrated. Moreover, by measurements of airway resistance it could be shown that in diseased and normal lungs of unmature infants the range of laminar flow is low due to the lability of the bronchial walls. A new method of valuation of the experimental data using the laws of alternating current (Heusinger) has been proven to be useful in the analysis of pulmonary mechanics.


Florid epithelioid cell and sarcoid-type reaction associated with non-Hodgkin's lymphoma. Five patients suffering from non-Hodgkin's lymphoma associated with an intense infiltration of epithelioid histiocytes and even sarcoid-type granulomas in the involved tissue are described. A similar tissue reaction, at both involved and uninvolved sites, has been described in patients with Hodgkin's disease. The cause of this reaction may be immunological; its prognostic significance still awaits elucidation. In the case of non-Hodgkin's lymphomas, it may cause difficulty in diagnosis of lymphoma and hence may result in unnecessary delay in the initiation of therapy.


Hashimoto's thyroiditis and its relationship to other thyroid diseases. The experience of the Medical University of South Carolina with Hashimoto's thyroiditis revealed an 8.3 per cent incidence of carcinoma. The most common type of carcinoma was an associated lymphoma. There was an additional 8.3 per cent incidence of a benign adenoma. Needle biopsy as a mechanism for diagnosing Hashimoto's disease, we believe, is inaccurate. A larger aliquot of tissue should be removed for the pathologist if there is a suspicion of an associated tumor. An open biopsy permits the pathologist to make an accurate diagnosis with a minimal amount of morbidity.


Total body irradiation in non-Hodgkin lymphoma and its effect on bone marrow and peripheral blood. Patients with non-Hodgkin lymphoma have been treated with total body irradiation (T.B.I.). Very high remission rate is obtained in lymphosarcomas, but response in histiosarcoma is extremely poor. Bone marrow study suggests that marrow depression following T.B.I. is transient and complete recovery occurs provided the bone marrow is not already compromised by previous chemotherapy and radiation therapy. Extreme caution is required when T.B.I. is repeated as this may lead to progressive marrow hypoplasia.


Metabolism of 17beta-hydroxy-2alpha-methyl-5alpha-androstan-3-one in the rabbit. The neutral urinary excretion products of 17beta-hydroxy-2alpha-methyl-5alpha-androstan-3-one from the rabbit dosed orally were investigated. Together with oxidation-reduction of the oxygen functions at C-3 and C-17 hydroxylation occurred at C-15, C-16, and at the 2alpha-methyl positions of the steroid nucleus.


Primary lymphosarcoma of prostate.

Primary lymphosarcoma of prostate. A case of primary lymphosarcoma of the prostate in a seventy-one-year-old patient is presented. He had palliative surgical treatment and radiotherapy but died seven months later of heart failure with signs of metastatic disease. Treatment of this condition should include surgery and irradiation. Only its early discovery might change the prognosis.


[Peridural anesthesia in operations for toxic goiter]. The authors employed peridural anesthesia in 92 patients with thyrotoxicosis According to their findings peridural anesthesia produced favourable shifts in the status of the cardiovascular system and ventilatory apparatus. Peridural anesthesia is considered to be a more acceptible method of anesthesiological provision in patients with toxic goiter than infiltrationanesthesia and intratracheal fluothane anesthesia.


[Molecular heterogeneity of blood and liver catalase rats with tumors]. By the method of gel-chromatography on sefadex G-200 and electrophoresis in polyacrylamid gel molecular forms of blood and liver catalase were isolated in rats with transplantable Pliss lymphosarcoma. Under study were changes in microheterogeneity of the enzyme, its activity and kinetic parameters in the kinetics of tumor growth. Quantitative and qualitative changes in the parameters under investigation were found already on the second day after tumor transplantation. These changes are enhanced with tumor progression.


[Tumors of the mesentery of the small intestine]. The clinical picture of solid tumors of the intestinal mesentery is varied and depends on the character of growth (benign, malignant), size and anatomical variants of tumor localization in the mesentery. Sometimes, the tumors concerned can induce pseudosyndrome of acute abdomen or inflammation of the adjacent organ secondary involved by tumor. Among complications induced by tumor are as follows: intestinal hemorrhage, peritonitis and acute or partial intestinal obstruction. The roentgenological picture of intestinal mesentery tumors shows some characteristic features. Eight observations of the author are reported.


Methods to purify and determine rubratoxins. Rubratoxin were recovered from cultures of Penicillium rubrum after the mold grew in natural substrates, a semi-synthetic medium, and a glucosemineral salts broth. Substrates that contained rubratoxins were extracted with: diethyl ether, ethyl acetate-benzene, ethanol (100%), ethanol-acetone, acetonitrile, or diethyl ether with refluxing at 45 degrees C. Extracts were screened for rubratoxins by thin-layer chromatography. Some extracts were partially purified with a column of silicic acid using acetone as the eluant. Other extracts were purified (primarily removal of pigments) using columns of silica gel plus Celite and gradient solvent elution. Most rubratoxin B (1.9 mg/g or 0.77 mg/ml) was recovered when corn, rice, or glucose-salts broth were extracted successively with diethyl ether, ethyl acetate-benzene, and diethyl ether or when samples were adjusted to pH 1.5 before refluxing with diethyl ether at 45 degrees C for 1--4h. Most rubratoxin  A (0.1--0.15 mg/ml or 1.0 mg/g) was obtained from samples of corn extracted twice each with ethyl alcohol, acetone, and ethyl acetate; from glucose-mineral salts broth extracted with diethyl ether; or from yeast extract sucrose broth extracted with diethyl ether and refluxed for 4 h at 45 degrees C. Large amounts of fairly pure rubratoxin A (up to 400 mg) and rubratoxin B (greater than lg) were obtained with a combination of preparative thin-layer and column chromatography.


Analogues of human calcitonin. V. Influence of basic amino acids in positions 11, 17 and 24 on hypocalcaemic activity in the rat. The influence of positions 11 and 24 on hypocalcaemic potency and duration of action was examined. These positions are respectively occupied by threonine and glutamine in HCT, but by the basic amino acids lysine and arginine in SCT. Replacement of threonine by lysine trebled the hypocalcaemic potency of HCT and slightly prolonged its duration of action. Substitution of arginine for glutamine reduced the activity to about one tenth. The simultaneous introduction of both basic amino acids yielded an analogue intermediate in activity between those obtained by the single substitutions. The analogue [Bmp1, Va18, Lys11, Arg24]-HCT displayed the same effects as [Lys11]-HCT.


Short time kinetics of deoxycorticosterone, deoxycortisol, corticosterone and cortisol during single dose metyrapone test. In 4 young healthy males, serum levels of 11-deoxycortisol (S), cortisol (F), 11-deoxycorticosterone (DOC) and  corticosterone (B) were determined at short intervals after oral administration of 30 mg/kg of metyrapone (M) at midnight. 11-hydroxylase blockade was calculated from the formula (formula: see text). Significant blockade was demonstrable 15 to 30 min after drug administration. Maximum blockade (greater than 90%) was found between 2 and 4 a.m., and fell to 60-70% at 8 a.m. The profile of blockade was very similar in all the subjects, although the absolute early rise in steroid levels showed large inter-individual differences. The F level at 8 a.m. (only slightly suppressed under these conditions) is not a safe indicator of adequate 11-hydroxylase blockade.


Indirect evidences of prolactin involvement in precocious puberty induced by hypothalamic lesions in female rats. The effects of 2-bromo-alpha-ergocryptine (CB-154) administration in maturing female rats with precocious puberty induced by hypothalamic lesions, as well as the milk secretion rate in these animals after their first parturition were studied. Treatment with CB-154 inhibited precocious vaginal opening induced by hypothalamic lesions. After the treatment with the derivative was terminated, the ovulatory response was not different from that of intact control rats. After their first parturition lesioned rats accumulate milk at a faster rate, following an initial depletion period than their non-operated controls. These results suggest than an alteration in prolactin release may be involved in determining the precocious puberty induced by lesions of the anterior hypothalamic area.


[Preventive effect of tribenoside in spontaneous arthrosis of the mouse]. Tribenoside, a D-glucofuranose derivative, was administered prophylactically over a period of ten months to six-month-old mice of the C 57 Black strain (Animal Breeding Unit, Sisseln), which are known to have a predisposition to spontaneous gonarthrosis. The preparation was given once daily for five consecutive days every other week in doses of 100 or 300 mg/kg p.o. At the end of the treatment period, serial sections of both knee joints were examined. In the placebo-treated controls, arthrotic lesions of varying severity were found in 97% of the specimens. In the animals given tribenoside in either dosage arthrotic lesions were significantly less frequent and less severe. The number of animals with bilateral gonarthrosis and of those with proliferative changes was also significantly or highly significantly smaller in the groups treated with tribenoside than in the controls. The only indication of a dose-related effect of the preparation was the fact that arthrosis of the most severe grade was present in fewer animals in the group treated with the higher dose. At present, the mechanism of action responsible for the protective effect of tribenoside demonstrated once again in these experiments cannot be clearly defined.


Effect of piperazine oestrone sulphate on serum lipids and lipoproteins in menopausal women. Twenty menopausal women and 2 women with gonadal dysgenesis were treated with piperazine oestrone sulphate 1.5-3 mg dialy on a cyclical basis for a period of 6 months. Fasting serum lipids and lipoprotein esterified fatty acid indices (EFI) were estimated before starting treatment and after 3 and 6 months. There were small falls in serum cholesterol (significant at 3 months) and beta-lipoprotein EFI (significant at 6 months). Serum triglyceride and pre-beta-lipoprotein EFI rose significantly at both 3 and 6 months. Serum total phospholipid levels were reduced (significant at 6 months) with most marked changes in the sphingomyelin fraction. Other parameters were not significantly altered.


The role of follicle-stimulating hormone (FSH), in combination with luteinizing hormone (LH), in oestrogen-induced ovulation during the oestrous cycle in the rat. Studies were undertaken to determine the role played by FSH in oestrogen-induced ovulation in 4-day cyclic female rats. About one half of the experimental animals receiving 10 microng oestradiol benzoate (OeB) subcutaneously, on the morning of dioestrus I, displayed luteinization or/and ovulation, when sacrificed on the morning of expected pro-oestrus. Pento-barbitone administered on dioestrus II at 18.00 did not prevent this action of OeB. A simultaneous LH and FSH surge was observed in the serum of half of the OeB-treated females killed by decapitation of dioestrus II at 17.30. The LH surge was decreased in OeB-treated females bled by cardiac puncture under pentobarbitone anaesthesia at dioestrus II at 17.30. This bleeding procedure almost completely suppressed the luteinizing effects of OeB. It was concluded that i) OeB caused a synergistic release of LH and FSH ii) bleeding by cardiac puncture as such may constitute a source of inhibition of OeB-induced luteinization.


Rat endometrium enzymes in 4-day oestrous cycle and early pregnancy. The specific activities of lactate dehydrogenase (LDH) and its M-type (M-LDH), beta-glucuronidase (beta-GR), acid phosphatase (ACP) and alkaline phosphatase (AP) were determined. The specific activities of the enzymes (LDH, beta-GR) in the myometrium were lower and their changes less pronounced than in the endometrium. We, therefore, determined the enzymes in the rat endometrium only in further experiments. All enzymes react sensitively to the changes induced in the endometrium by endogenous hormones in the course of a 4-day cycle: pro-oestrus (P) is characterized by rather low enzyme activities, oestrus (E) by a peak of LDH and M-LDH and a rise of AP. In metoestrus (M) there is a peak of beta-GR, ACP and AP. Dioestrus (D) is characterized by a significant decrease in LDH and M-LDH and by elevated values of all the other enzymes. The values on the individual days of the 4-day cycle were compared with days 4-6 of pregnancy. The reason for this was that if the rats were not mated, they would, respectively, return to pro-oestrus instead of being 4 days pregnant, to oestrus instead of being 5 days pregnant, or to metoestrus instead of being 6 days pregnant. We found the following differences: on day 4 of pregnancy LDH and M-LDH were lower and ACP and AP higher than in P. On day 5 of pregnancy the LDH, M-LDH, beta-GR and AP were lower than in E. On day 6 of pregnancy the LDH, M-LDH, ACP and especially beta-GR, were lower than in M.


Evidence for a dopaminergic component in the series of neural events that lead to the pro-oestrous surge of LH. The possible participation of dopamine in the neural events that lead to the pro-oestrous surge of luteinizing hormone (LH) was investigated utilizing a dopaminergic ergoline derivative (lergotrile mesylate). Administration of reserpine (2.0 mg/kg, ip) to rats on the day of pro-oestrus depleted brain dopamine and norepinephrine and prevented the LH surge and ovulation. Administration of legotrile mesylate prior to or at the same time as reserpine prevented the inhibitory effects of reserpine on LH release and on ovulation in about half of the animals. When lergotrile mesylate was given on the morning of pro-oestrus, the LH surge was advanced. The results indicate that there is a dopaminergic component in the series of neural events that precede the surge of LH on pro-oestrus, and that the dopaminergic stimulus precedes the LH surge by about 4--5 h.