Serotyping of Pseudomonas aeruginosa isolated from clinical specimens.

Serotyping of 168 clinical isolates by the slide agglutination test using TIBS (Toshiba Institute of Biological Science) serotyping sera, which were prepared from Homma's serotype strains at the request of Pseudomonas aeruginosa Serotype Committee in Japan, was performed and the results were compared with serotyping using IMSUT (Institute of Medical Science, University of Tokyo) serotyping sera by the tube agglutination test. When heat-killed antigen from clinical isolates were used, both sets of serotyping sera showed similar results and the slide agglutination test using TIBS serotyping sera could be substituted for the tube agglutination test using IMSUT sera. It was also discovered that serotyping by the slide agglutination test with TIBS serotyping sera could be carried out using live bacteria. However, in serotyping with live bacteria, there is some difficulty in observing the agglutination time. To solve this problem, we propose that positive agglutination should be determined within 60 sec. The authors also performed serotyping of the clinical isolates using Difco serotyping sera prepared by the Difco Company based on Liu's serotyping system, and the results were compared with those obtained with serotyping sera prepared with Homma's serotype strains. The results indicated that in serotyping of clinical isolates using Difco serotyping sera more cross reaction occurred than in serotyping with sera obtained from Homma's serotype strains.


The enhancement of phagocytosis and intra-cellular killing of Pseudomonas aeruginosa and its common antigen (OEP) coated latex particles by mouse spleen macrophages to which anti-OEP-IgG and gentamicin have been added.

This experiment was performed using macrophages derived from mouse spleens immunized or non-immunized with the common antigen (OEP) of Pseudomonas aeruginosa. The phagocytosis of these macrophages of live or formalin killed Pseudomonas aeruginosa and latex particles coated with OEP were enhanced by the addition of anti-OEP-IgG, but not by immunoglobulin taken from normal mice. The macrophages from mice immunized with OEP showed significantly enhanced phagocytosis of latex particles coated with OEP, but not of live or killed bacteria. The effects of anti-OEP-IgG and gentamicin on phagocytosis and intracellular killing were compared in cases where only anti-OEP-IgG or only getamicin were used as well as in cases where the two were combined. It was found that the two combined was far more effective on phagocytosis and intracellular killing. Furthermore, there was little or no difference in the results depending on whether macrophages from mice immunized or non-immunized with OEP were used.


The effect of amino acids, carbohydrate and fat emulsion on the metabolism in gastrectomized patients.

Nitrogen balance and other metabolic activity can be maintained by adequate calorie and protein supply during immediate postgastrectomy period. Despite high intake of protein, great loss of nitrogen seems to occur in urine during infusion with polyalcohol sugars as compared with natural sugars, e.g., glucose, fructose and maltose. The best utilization of amino acids resulting in positive nitrogen balance and energy utilization were shown to be achieved by combined use of Intralipid, glucose, maltose and essential as well as non-essential amino acids in the clinical and laboratory studies.


[Study of the pulmonary vessel reaction to administration of carbon dioxide and nitroglycerin in congenital heart defects complicated by high pulmonary hypertension].

The results of functional pharmacological tests with nitroglycerine and carbon dioxide gas are presented for patients with congenital heart diseases and pulmonary hypertension, as shown during right heart catheterization. It was established that nitroglycerine, taken sublingually, does not produce any direct effect on the pulmonary artery pressure, and the delayed changes in haemodynamics are a consequence of the altered regimen of pressure in the general circulation. When carbon dioxide gas was administered into the pulmonary artery, it proved to produce a direct effect upon the receptors of the pulmonary arterial bed. However, along with the hypotensive effect, in some cases the carbon dioxide gas increases the pressure in the pulmonary artery due to the embologenic effect of the gas bubbles. Both agents affect the arterial pressure irrespective of the patient's age, the nature of the heart disease, and the degree of pulmonary hypertension.


[Changes in the thyroid hormone system with combined anticonvulsion treatment of epileptic children and adolescents (author's transl)].

Anticovulsant combined treatment produces statistically significant reduction of total thyroxine, free thyroxine and protein-bound iodine. Total cholesterin is significantly raised on average of the total. Basal concentration of thyreotropic hormone is slightly lowered. The extent of changes is rather greater than with Valproat-, Diphenylhydantoin- and primidon permanent treatment; it corresponds with that seen in long term Carbamazepin treatment. No definite combinations of anticonvulsants could be found which would act in a particularly unfavorable fashion on the thyroid hormone system. In double combinations the changes in serum concentrations were the same as in triple combinations. The action of combined treatment in permanent treatment with single drugs is thought to be due to a removal of T4 from the transport protein link and induction of liver enzyme, which produces rapid conversion and metabolizing of T4. A hypothalamic action of combined antoconvulsants is discussed.


Sex hormones correlated with sex skin swelling and rectal temperature during the menstrual cycle of the pigtail macaque (Macaca nemestrina).

Daily measurement of serum luteinizing hormone, estradiol-17beta, and progesterone were made during the menstrual cycle in nine pigtail macaques (Macaca nemestrina). All data were normalized to the day of the luteinizing hormone peak. Serum estradiol-17beta increased from approximately 100 pg/ml during the early follicular phase to 442 +/- 156 pg/ml during the maximum midcycle concomitant with the luteinizing hormone peak, and a small increase in serum estradiol-17beta was observed during the luteal phase coincident with the progesterone peak. Serum progesterone values increased slightly at the time of the luteinizing hormone peak and increased from 0.2-0.3 ng/ml during the midfollicular phase to peak levels of 8.3 +/- 1.75 ng/ml 9 days after the luteinizing hormone surge. Serum luteinizing hormone remained low and relatively constant throughout the early and midcycle, then sharply increased approximately four-fold to peak values of 6.25 +/- 0.9 ng/ml. Sex skin swelling increased slowly during the follicular phase and declined slowly throughout the early luteal phase. Rectal temperature did not change significantly throughout the menstrual cycle. The similarity of plasma sex hormone changes during the menstrual cycle between women and the pigtail macaque suggested that this nonhuman primate should be a useful animal model for studying human reproduction.


A head enclosure for exposing monkeys to selected gas mixtures.

An acrylic head enclosure, permitting rapid exchanges of atmospheric gases, was developed for investigations of physiologic and performance responses of small nonhuman primates to graded hypoxic hypoxia and hypercapnia. The total system included a neck yoke plate which served both as a physical barrier to arm and hand movements in the head area and as a base on which to rest the head enclosure. The transparent, airtight, head enclosure permitted rapid exchanges of controlled gas mixtures and the execution of performance tasks in an apparently comfortable experimental environment.


Changes in hemodynamic parameters, inotropic state, and myocardial oxygen consumption owing to intravenous application of nitroglycerin.

Changes in hemodynamics, inotropic state, and myocardial oxygen consumptom were investigated in a total of 70 patients with coronary disease after intravenous application of nitroglycerin (0.4 mg., 0.2 mg., and 2 mg. per hour). The results demonstrate that nitroglycerin enlarges therapeutic possibilities during and immediately after operations in patients with limited coronary reserve. The decrease in myocardial oxygen consumption, dependent on dose, ranged between 15.8 and 22.9 per cent.


Mobile health services: a study in cost-effectiveness.

The techniques of cost-effectiveness are employed to simplify resource allocation decisions concerned with the use of land and air transport systems in the health services of a developing country. Outcome classifications are produced for patients seen by mobile and fixed primary care units. The mobile services examined were far more costly (8 to 14 times greater) per likely-effective-patient-contact than comparable care delivered from permanently staffed fixed clinics. This was particularly so for the air-delivered service. The disparity in cost-effectiveness was due mainly to the small proportion of patients seen by the mobile services who could be treated effectively in contrast to a far larger proportion at fixed clinics. This was a consequence of the periodic availability of care from the mobile services as against the continuing provision of care at fixed clinics. The main justification for the use of mechanical transport in connection with primary health care is regular supportive (not policing) visits by skilled health workers to rural clinics. Land vehicles are cheaper than aircraft for visiting the more accessible facilities; for the more distant clinics, the cost of journeys by land vehicle are similar to those by aircraft.


Bone remodeling and calcium metabolism: a correlated histomorphometric, calcium kinetic, and biochemical study in patients with osteoporosis and Paget's Disease.

The extent to which histomorphometric analysis of bone biopsies correlates with Ca kinetic and biochemical parameters to reflect true bone formation and resorption in adult man remains an unsolved issue. Two groups of patients with either low (osteoporosis), (n = 15) or high (Paget's disease, n = 6) bone turnover were studied before and after sodium fluoride (NaF) and diphosphonate (EHDP) treatment, respectively. Histomorphometry of iliac crest biopsies permitted precise quantitation of the osteoblast layers (SVab), osteoid seams (SVos), the number of osteoclasts (NAocl) and the Howship's lacunae (SVhl). These determinations were correlated with serum alkaline phosphatase (aPh), urinary hydroxyproline (HyPro), Ca accretion rate (Vo+), and Ca mobilization rate (Vo-). In both patient groups bone formation indices were significantly correlated: SVob/Vo+, r = 0.85; SVos/Vo+, r = 0.83; and aPh/Vo+, r = 0.97. Provided that bone matrix formation and mineralization progess at the same rate, bone formation may be assessed by measuring either aPh, Vo+, SVob, or SVos. From these correlations it is not possible to draw any conclusions regarding the absolute "true" value of bone formation, be it in terms of Ca kinetics, alkaline phosphatase, or histomorphometry. However, since Vo+ retains its proportionality to all the other bone formation parameters tested, the so-called "slow exchange," which refers to pure physicochemical Ca exchange processes in the bone mineral, does not perturb Vo+ in an unsystematic way. Vo+ as well as aPh and histomorphometric indices are thus reliable, though not absolute indices of bone formation. Bone resorption indices correlated less well than bone formation indices: NAocl/Vo-, r = 0.68 and SVhl/Vo-, r = 0.63 with both groups. In the osteoporotic group, a negative correlation existed between the empty Howship's lacunae SVhe and Vo+, r = -0.62. Consequently, the overall extent of Howship's lacunae SVhl is influenced both by bone resorption and bone formation. On the other hand, the best correlation of HyPro was with the sum of Vo+ and Vo-, r = 0.97, confirming that HyPro is a sensitive index for the change of bone turnover.


Evidence that the multi-drug-resistance of Streptococcus faecalis BIO-4R is not carried by a plasmid.

The multi-drug-resistant strain Streptococcus faecalis BIO-4R was studied to see if it carried a plasmid responsible for antibiotic resistance. From results indicating that the antibiotic resistance of S. faecalis BIO-4R was not transferred to recipient bacteria, that the organism did not produce enzymes which inactivated antibiotics, and that the presence of covalently closed circular DNA was not demonstrated by dye-cesium chloride buoyant density gradient centrifugation, it was concluded that the organism did not carry such a plasmid. Studies on polyphenylalanine synthesis by cell-free extracts of the oganism showed that its ribosomes were resistant to chloramphenicol, tetracycline, streptomycin and kanamycin. These results, although rather indirectly, support the above notion that the multi-drug-resistance of S. faecalis BIO-4R is not mediated by a plasmid.


[Electron microscopic study of dark and photo-oxidative degradation of the blue-green alga Anabaena variabilis].

Changes in the cell ultrastructure were studied during incubation of the obligate phototrophic blue-green alga Anabaena variabilis in the dark for a long time. The cells lost viability though their cell wall and cytoplasmic membrane were preserved; however, certain regions of the mureine layer were thickened in some cells. The membranes of the photosynthetic apparatus separate forming intrathylakoid spaces and the cytoplasm density decreases revealing phycobilisomes. During incubation in the dark for a long time, polyglucoside alpha-granules in the cytoplasm disappear, polyhedral bodies are preserved, and numerous large granules of average electron density and unknown nature appear. Transfer of the culture from the dark to the light when the cells are losing their viability results in intensive destruction of the thylakoids. Loss of viability by the cells of Anabaena variabilis in the dark is supposed to be due to irreversible damages of the membranes of the photosynthetic apparatus in these conditions.


[The results in our tuberculosis laboratory with penicillin blood agar medium].

A comparison of Löwenstein - Jensen and penicillin blood agar media, which can be prepared in small laboratories, is made in routine diagnostic cultivations of Mycobacterium tuberculosis. Tuberculosis. Tubercle bacilli grown in Löwenstein - Jensen medium were inoculated in Löwenstein - Jensen and penicillin blood agar media in numbers of 100.000, 10.000, 1000 and 100 bacilli and their growth was detected in each medium. It was found that the growth in both media was the same Inoculations were made from 153 sputum specimens to each medium and 5 positive growth were obtained. 3 out of positive cultures were grown on both media, the other 2 positives were grown only on penicillin blood agar. None of the media showed contaminations. These findings suggest that the penicillin blood agar medium has at least the same, or even better qualities than the Löwenstein - Jensen medium.


[Characteristics of a continous culture of hydrogen bacteria under conditions of gas limitation].

The effect of the specific growth rate and limiting gas on the concentration of cells, the rate of gas utilization, and the economic coefficients was studied during continuous cultivation of Hydrogenomonas eutropha Z-1. Cell concentrations as functions of the specific growth rate with limitation by H2, 02, and CO2, were plotted as hyperbolae and were linear in the coordinates X, 1/D. The rates of gas absorption Q (M/1 - hr) grow linerly with the concentration of the cells in the culture. The economic coefficients are linear in the coordinates 1/y, 1/micron. The effect of the specific growth rate and kind of limiting gas on the ratios between absorbed H2, 02 and C02 is described.


[Role of cosubstrates in the microbiologic oxidation of xylene isomers by a culture of Pseudomonas aeruginosa].

Cosubstrates (additional substrates) produced different effect on transformation of isomeric xylenes of Pseudomonas aeruginosa 7. The cosubstrates manifested the highest stimulating effect on transformation of o-xylene, on which the culture did not grow, and p-xylene, in the presence of which only a weak growth was detected. The most effective cosubstrates were xylose and maltose which were actively oxidized by the culture but could not serve as carbon sources. One of mechanisms of the cosubstrate action is inhibition (or repression of synthesis) of the enzymes responsible for oxidation of toluic acids by the cosubstrates or their metabolites, which results in their accumulation in the medium. Addition of cosubstrates can regulate transformation stimulating accumulation of different products.


[Severe toxic liver injury after overdosage of parenteral administered carbohydrates: a case report (author's transl)].

A 31-year old female patient with anorexia nervosa developed a severe toxic liver injury after parenteral hyperalimentation. Over a period of five days she received a total amount of carbohydrates of 0.47-1.07 g/kg/hr consisting of glucose, fructose and the polyalcohols sorbitol and xylitol. A steep rise in SGOT, SGPT, and GLDH were noted as well as prolongation of the prothrombin time and decrease of the clotting factors; uric acid and lactate increased, serum phosphate decreased. After termination of parenteral hyperalimentation a laparoscopy and liver biopsy were performed. The liver biopsy revealed by light- and electronmicroscopy signs of a severe toxic liver injury. After reduction of total carbohydrates and later oral feeding a complete remission occurred. The cause of the toxic liver lesions was believed to be due to an overdosage of fructose and sorbitol.


[Amino acid composition of polynucleotide-peptide complexes isolated from algae].

The amino acid composition of the peptide moiety of sulphur containing polynucleotide-peptide complexes (S-PNPC) was studied with four species of green algae and two species of blue-green algae. S-PNPC contained almost all amino acids which were usually encountered in acid hydrolysates of proteins, and also unidentified ninhydrin-positive compounds. The amino acid composition of the peptide moiety of S-PNPC was rather similar in the case of different algae, and was characterized by the prevailence of acid amino acids.


[Ability of obligate methylotrophs to perform nitrogen fixation].

The ability for nitrification was studied among mesophilic and thermophilic cultures of obligate methylotrophs Methylobacter ucrainicus, Methylomonas methanica, and Methylococcus thermophilus. The strains were almost incapable of nitrification under autotrophic conditions. In the presence of methane, however, they oxidized NH+4 TO NO-2: over 150 mg/litre NO-2 nitrogen was found in the cultural broth. Therefore, obligate methylotrophs are capable of heterotrophic nitrification. The level of nitrification suggests that it is not a side reaction but a necessary stage of the metabolism of obligate methylotrophs. The phenotype relation between obligate methylotrophs and nitrifying organisms is discussed.


The porcine heart valve prosthesis.

The development of the prosthetic heart valve has led to the evolution of cardiac intensive care units, a better understanding of cardiac function and biocompatible materials, and new surgical procedures. Initial efforts with formaldehyde-fixed valves did not have long-term success. They led to the development of the stabilized glutaraldehyde process (SGP) valve and the flexible stent. The safety and efficacy of a heart valve bioprosthesis has been demonstrated through laboratory and animal experiments. Data on long-term clinical implants are needed to validate the results of these experiments.


From valvular xenograft to valvular bioprosthesis (1965-1977).

The development of a bioprosthesis was generated by recognition of its important potential advantages over a mechanical prosthesis. Considerations of choices of animal and tissue sources, preparation procedures, and patient applicability led researchers from the allograft to xenograft, and then to the valvular bioprosthesis. At the present time, glutaraldehyde-preserved xenograft valves appear to be a reasonable alternative in valvular replacement. Their limited durability must be weighed against the disadvantages of a mechanical prosthesis in deciding which to use.


Mitochondrial biogenesis: inhibitors of mitochondrial protein synthesis.

The effects of erythromycin, chloramphenicol, cycloheximide, pyrimethamine, chromate, cadmium, lead, nickel, 4-nitro-quinoline-1-oxide and thioacetamide on yeast and human cells were studied. Inhibition of the synthesis of mitochondrial proteins resulted in the loss of cytochromes as well as in morphological changes in the cellular membranes and mitotic arrest. The data are discussed.


Buoyant density fractionation of Drosophila melanogaster chromatin.

Buoyant density fractionation of Drosophila melanogaster chromatin utilizing low molecular weight molecules such as actinomycin-D to induce changes in buoyant density has been investigated. Fractions of chromatin containing identifiable repeated DNA sequences could be isolated using actinomycin-D as the selective agent. Protein displacement from the chromatin complex was found to be a prerequisite for the observed buoyant density changes.


[Epidemiology of dental caries (author's transl)].

More than 99% of the population of North and Central Europe and also North America suffer from dental caries. Epidemiological studies on the spread and course of this, perhaps the most common disease of mankind, and on the state of dental care and the efficacy of preventive measures are consequently of great social hygienic and health political significance. Methods of obtaining information (including time-saving and yet permissible partial registration), the difficulties of caries diagnosis and the demands for highly informative statistics on caries are discussed. The importance of nutrition and oral hygiene for the prevention of caries is emphasized. But it must be expressed that at present there is no alternative, apart from the use of fluorides (drinking water, tablets, salt etc.), for an effective mass prophylaxis of dental caries.


[Immunological aspects of caries prophylaxis (author's transl)].

The bacteriological and immunological principles for the development of a vaccine against dental caries are presented in a short survey. The potential cariogenic Streptococcus mutans is the center of interest of this special area of research in caries prophylaxis because of its peculiar characteristics. In animal experiments, the protective effects of attempts to immunize with this cario-etiologically relevant species of streptococcus or its metabolic products differed and were sometimes contradictory. Also conditions in the human show no distinct connection between the dental status and the appearance of specific antibodies against Strept. mutans antigens. The pertinent literature cannot answer the question whether and when an effective vaccine against dental caries can be produced at the present time.


[The diagnosis of functionally induced disturbances in the region of the masticatory apparatus (author's transl)].

Functionally induced disturbances in the region of the masticatory apparatus are frequently due to occlusal interferences. The clinical investigation must not, however, be limited to testing the occlusion of the teeth alone; it includes the examination of the muscles of mastication and the mandibular joint. The exact investigation of the occlusion is performed by instrumental analysis of function. It is the method of choice for determining the position of the mandible. A recording of the findings ought to suggest the technical methods of investigation on which the diagnosis is based.


[Significance of plaques for the etiology of caries and marginal periodontopathies (author's transl)].

The genesis of dental caries and marginal periodontopathies has a conclusive connection with dento-gingival plaque. Plaque is a constantly regenerating accumulation of salivary constituents and especially of various oral micoorganisms. Microbial decomposition of sugars from the food produces acids from fermentation which lead to local demineralization of the teeth and carious destruction. Antigenic plaque substances cause immunological reactions. With persistent bad oral hygiene, a gingivitis may develop into a progressive periodontitis with deepened gingival pockets.


[Tongue as a reflector of cerebral and articulatory dysfunction. Tongue motility test for three- to five-year-old children].

The tongue motility test has been developed to test the motility of the tongue in three- to five-year-old preschool children. It examines the resting position of the tongue and the mobility of the tongue in relation to 9 different movement patterns of varying degrees of difficulty. The result of the test is represented by the number of points obtained (minimum = 0, maximum = 10). The results of a routine investigation of 865 children provide the normal value for the tongue motility test. This is especially related to the age and less to the sex of the subject. The significance of the tongue motility test for the diagnosis of "minimal cerebral dysfunction" and for the investigation of the stage of articulatory development of a child is discussed.


[Antibacterial therapy of urinary tract infections. Results of a clinical trial with the combination sulfamoxol/Trimethoprim (= CN 3123) (author's transl)].

In the present paper, the use of the combination preparation sulfamoxol/trimethoprim (CN 3123, Nevin [Grünenthal], Supristol [Nordmark]) in urinary tract infections is reported. This preparation was used in 165 patients of both sexes and all ages. The initial dose was 2 tablets followed by a maintenance dose of 1 tablet every 12 hours for a treatment lasting 10 days on the average. The preparation led to asepsis in 69% of the patients with chronic urinary tract infections if the organisms were sensitive in vitro. In asymptomatical urinary tract infections complicated by fistula and transurethral indwelling catheters, on the other hand, elimination of organisms was only attained in 46%. In our opinion, antibiotic therapy is not indicated in these patients only after taking off the indwelling catheter.


[Patient physiognomy-- the picture of the patient: (author's transl)].

The facial expression of the patient has demonstrably occupied doctors with regard to diagnosis and prognosis even in ancient times. Physiognomy found acceptance in the medicine of modern times, particularly through the publications of Johann Caspar Lavater (1741-1801), Carl Gustav Carus (1789-1869) and then, after 1838, of Karl Heinrich Baumgärtner (1798-1886) who took advantage of lithography, which had just come into use, to reproduce pictures of patients. In the thirties of our century, patient physiognomy has undergone a renaissance (Killian, Fervers, Risak, Lange and others) which was repeated in the sixties. In the last decades, the interest was almost always an expression of dissatisfaction with an exclusively scientifically oriented medicine.


[Comparison of contraceptive conduct of minors and of women of various ages (author's transl)].

In 1975, a random sample (n = 639) of the female population of the Greater Munich Area was taken for the research project on "side effects of oral contraceptives: development phase". The women were 12-45 years of age and were classified according to town/country and adult/adolescent. By means of a specially prepared questionnaire, the approach and behavior of the interviewees with regard to contraception and prohylaxis inter alia were recorded. 65% of all those questioned were examined gynecologically within the framework of the project. The data obtained by question and examination are at the disposal of the Institut für Medizinische Informationsverarbeitung, Statistik und Biomathematik (ISB) for evaluation of additional dialogue. The authors have compared the contraceptive behavior of minors ( = up to 17 years) with adults in a special evaluation of 350 cases aged from 12 to 30 years.


[Possibilities for nuclear medical investigation in the retroperitoneal space: (author's transl)].

The possibilities for nuclear medical investigation in the retroperitoneal space were extended by the introduction of the scintillation camera with an evaluation system. The diagnostic aid in diseases of the kidney (unilateral and bilateral nephropathies, shock kidney, stenosis of the renal arteries, aortic occlusion), suprarenals (Conn syndrome) and the skeleton of the entire body (diagnosis of metastases and non-malignant bone diseases) are reviewed. Scanning scintigraphy can be used in the identification of lymphnode metastases in negative (198 Au colloid) and positive (67 Ga) tumor contrast and in double radionuclide substraction techniques in pancreatic tumor and chronic pancreatitis. Clinical examples are demonstrated.


[Cystic degeneration of the vessel walls. The differential diagnosis of obliterative angiopathies: (author's transl)].

Cystic degeneration of the vessel wall is a rare disease predominantly localized in the region of the popliteal artery.  It appears in the frequent clinical picture of intermittent claudication. Two cases are presented. The etiology of this syndrome is not clear. The appearance of intermittent claudication, preferably in middle-aged men without risk factors is typical for an obliterative angiopathy. Angiophically there are smooth-walled stenoses or occlusions, especially of the popliteal artery, with an otherwise inconspicuous vascular system. The prognosis after surgical treatment by excision or resection is good.


[A simplified, Fully Enzymatic Cholesterol Determination: (author's transl)].

The advantages of enzymatic analysis compared to conventional methods are shown by an example of a simplified, fully enzymatic cholesterol determination. They are: high analytical precision, reagents which are easy to handle, no inhibition be metabolites. The poor correlation between enzymatic and chemical analysis requires new normal values. The following are recommended for cholesterol: normal up to 200 mg/dl, requiring control 200-250 mg/dl and pathological over 250 mg/dl.


[Otorhinolaryngological aspects of headache: (author's transl)].

Since about 20% of the patients in a headache clinic have ENT complaints an ENT specialist should be consulted for diagnosis and treatment. It is very important to know what structures in the head and neck are sensitive to pain for diagnostic and differential diagnostic purposes. Primary and secondary neuritis are headache mechanisms in otolaryngology and also tension headache, which is specially discussed. Rhinogenous contact headache and headache as cardinal symptom in various syndromes are also stressed as specific to ENT. Finally a scheme is given for investigating a headache patient from the otolaryngological point of view.


[Headaches and sinusitis: (author's transl)].

There is a frequent coincidence of headache and sinusitis. In acute sinusitis, the localization of the headache can yield good diagnostic clues, while chronic inflammations do not offer reliable diagnostic indications. Further characteristics of rhinogenous headache are: typical periodicity during the day, occasional disturbances of sensitivity in a specific cutaneous area and certain typical pressure points in the facial region.


[The Unerupted Tooth, a Cause of Pain (Casuistics): (author's transl)].

In view of the remarkable number of cases of gnathogenous headache it is advisable to submit headache patients to a thorough dental and radiological inspection, even in cases of anodontous jaws, in order to identify unerupted teeth. Such an examination with consequent dental or surgical thrapy can in many cases spare lengthy neurological diagnostic or therapeutic procedures, possibly in hospital.


[Commotio cerebri and headache: (author's transl)].

Headaches form an essential part of the syndrome after concussion of the brain. The origin of these may be extracranial (neuralgias in scar tissue and hematomas, neuralgiform headache as a result of injury to the cervical spine) as well as diffuse in the sense of vasomotr cephalalgia which are due to central regulation disorders of the circulation caused by psychogenic mechanisms and compensatory neurosis. Methods of therapy include the use of vasoactive substances especially for vasomotor cephalalgia, immobilisation and local anesthesia in neuralgias, and psychopharmocological as well as psychotherapeutic aid in psychogenic complaints.


[The exogenous toxicologic aspects of headache: (author's transl)].

Headache is the cardinal symptom in many chronic intoxication syndromes. Here we find a distinct increase in connection with noxas stemming from our civilization: In regions of industrial agglomeration there is an increase in CO concentration and in lead poisoning from exhaust gases. Engine detergents cause typical intoxication syndromes. Insecticides have caused mercurialism and DDT-poisoning as a result of chemical concentration in maritime animals. Similarly, chronic poisoning by the insecticide E 605 can have headache as a cardinal symptom. In addition, the increased use of pharmaceutical agents leads to more possibilities of chronic intoxication,


[Exercise treatment in vertebragenic headache: (author's transl)].

In treating vertebragenic headache, the segmental movement, the shortened postural muscles, the feeble phasic muscles and the wrong patterns of movement can be influenced by exercises. The techniques of some of these exercises are described, the importance of an exact diagnosis is pointed out.


[Drug therapy for headache: (author's transl)].

The absence of essentially new principles among the substances which have recently made their appearance on the market for the treatment of headache is conspicuous. We have learned, however, to take a holistic view of the complex problem of headache and to combine medication with all other therapeutic measures in a logical way and also to use medicines for their relevant indications and to use them together. We have been able to handle even "problem cases" with a history of many different therapeutic attempts. The rate of satisfactory therapeutic success over a longer time amounted to two thirds of these cases.


Mechanism of hycanthone mutagenesis: the induction of temperature-sensitive mutations in Drosophila melanogaster.

A total of 358 sex-linked recessive lethals induced by hycanthone methane sulphonate (HMS) were checked for temperature sensitivity, along with 239 EMS-induced lethals as a positive control. Only about 1-2% of the HMS-induced lethals were temperature-sensitive, in contrast to about 7-8% for EMS-induced lethals. This can be reasonably explained by assuming that in Drosophila, HMS mainly acts by inducing frame-shift mutations or deletions.


Ketoacidosis in pancreatectomized man.

We investigated the importance of glucagon in the development of diabetic ketoacidosis by withholding insulin from six patients with juvenile-type diabetes and four totally pancreatectomized subjects. Patients were fasting and had previously been maintained on intravenous insulin for 24 hours. In diabetic patients plasma glucagon concentrations rose sharply after withdrawal of insulin, and the increases were accompanied by a rise in blood ketone concentration of 4.1+/-0.7 (S.E.M.) and blood  glucose concentration of 12.5+/-1.8 mmol per liter by 12 hours. In the pancreatectomized patients, despite the absence of measurable glucagon, blood ketones rose by 1.8+/-0.8 and blood glucose by 7.7+/-1.5 mmol per liter. Thus, glucagon is not essential for the development of ketoacidosis in diabetes, as has previously been suggested, but it may accelerate the onset of ketonemia and hyperglycemia in situations of insulin deficiency.


Evaluation of tetracycline or penicillin and ampicillin for treatment of acute pelvic inflammatory disease.

To evaluate guidelines for outpatient treatment of acute pelvic inflammatory disease recommended by the Center for Disease Control we studied 197 afflicted women. The women were treated either with tetracycline or with procaine penicillin and ampicillin, and 92% were subsequently seen at least once to assess efficacy of clinical and microbiologic treatment. Neisseria gonorrhoeae was isolated from the lower genital tract in 68% of these women, and although they had a quicker symptomatic response than those with nongonococcal infection (P less than 0.01), the two regimens were equally effective in producing clinical cure. However, subsequent identification of a pelvic abscess was 10 times more common in women from whom N. gonorrhoeae was not isolated. Therapy for pelvic inflammatory disease must be empirical since it is impossible to distinguish clinically between gonococcal and nongonococcal infection, and our data indicate that both regimens recommended by the Center for Disease Control are effective.


[Behavior of selected veterinary preparations during industrial milk processing].

Since the extensive veterinary-hygienic treatment of herds with insecticidal veterinary preparations may lead to milk contamination, the authors studied the behaviour of some active agents (butonate, dichlorvos (DDVP), trichlorphon, naled, carbaryl, hexachloro-p-xylene and rafoxanide) during the industrial processing of milk to fluid milk, cream, butter, cheese and milk powder, and during the storage of these products. Small-scale model experiments served to investigate the effects of pasteurization (74 and 95 degrees C.), separation and churning as well as of the processing to milk powder and cheese. Analyses for residues were performed by thin-layer chromatography, colorimetry and with the aid of the isotope technique. From the viewpoint of milk processing, the use of TCP and, in part, that of DDVP may be considered as less critical due to their hydrophilic properties and rapid degradation. In view of their lipophilic behaviour, the use of butonate, carbaryl, rafoxanide and hexachloro-p-xylene as active agents in veterinary preparations for milk cows must be regarded as problematic. The utilization of naled is also problematic due to the fact that the toxicology of its metabolites is not yet sufficiently known.


Precipitating antibody against protease of Corynebacterium pyogenes in pigs.

Antibody in sera from pigs carrying an abscess associated with Corynebacterium pyogenes and healthy pigs was examined by the agar gel diffusion test. In the test, the concentrated culture fluid containing the protease of C. pyogenes was used as antigen. As a result, precipitating antibody was demonstrated in sera from 25 of 30 abscessed pigs and a few of the healthy pigs. When the relationship between precipitating antibody and protease was examined by the immunoelectrophoresis and gel filtration of the concentrated culture fluid, the antibody was shown in the same position as the protease. From the result, it was clear that the precipitating antibody was against the protease of C. pyogenes. All the proteases produced by 27 strains of C. pyogenes of porcine and bovine origin were serologically identical with one another. They were, however, serologically different from those of Staphylococcus aureus, Bacillus cereus, and B. subtilis. In the inhibition test, the proteolytic activity of C. pyogenes was inhibited by the serum of the abscessed pig. It was also inhibited by healthy pig serum. From the results, it seems that the determination of precipitating antibody may be useful for the diagnosis of C. pyogenes infection.


Degradation of hypothalamic hormones.

The enzymatic fragmentation of TRH (pyroGlu-His-Pro-NH2) by serum, hypothalamic and hypophyseal tissue was investigated. As primary cleavage product only His-Pro-NH2 was detected when TRH was incubated with serum while with the tissue preparations the formation of His-Pro-NH2, deamido-TRH and prolineamide could be detected as enzymatically formed primary fragments.


Renal failure in familial lecithin-cholesterol acyltransferase deficiency.

Familial lecithin-cholesterol acyltransferase deficiency is a hereditary disorder of lipid metabolism. Lipid material is deposited in the kidneys, the glomerular capillary basement membrane is irregularly thickened, detachment and even loss of endothelial cells are seen in the glomeruli. Proteinuria was present in 8 out of 9 cases studied, usually it has not been detected before the age of 15-20. After 15-30 years with symptomless proteinuria, terminal renal failure has developed in 6 of the patients. Possible pathogenetic mechanisms of the renal damage is discussed; a large-molecular-weight low-density lipoprotein is suggested to be an important factor.


[Effect of gamma-hydroxybutyrate on EEG pattern in epilepsy. Preliminary report].

Investigations were carried out in 50 patients with epilepsy who had been subjected previously to careful clinical examination. For the investigations the preparation Gamma-OH EGIC was used in doses of 0.03 g/kg of body weight in rapid intravenous injection. The preparation modified rapidly the EEG tracings which were divided into 4 phases: 1) phase of initial resting record, 2) disappearance of alpha rhythm with increase of medium and low-voltage theta rhythm, 3) high-voltage phase resembling sleep activity with prevalence of delta rhythm, 4) phase of desynchronization--return of normal activity. Out of 50 epileptics in 31 cases temporal-lobe epilepsy was present, in 15 the seizures and EEG changes were generalized, in 4 cases focal non-temporal-lobe epilepsy was recognized. Administration of Gamma-OH to epileptics caused in 100% of cases a modification of the initial tracings and in 84% activation of EEG changes mainly with activation of focal slow-wave activity; in cases of minor absence attacks the drug always induced paroksysmal activity. The preparation is safe and non-toxic and may be used in outpatient clinics. It seems that activation of EEG changes in epileptics by Gamma-OH administration may be due to disturbances of the equilibrium between the structures activating and inhibiting the reticular formation of the brain stem and cerebral cortex.


[Thyroid activity in patients with myasthenia].

In 27 patients with myasthenia thyroid function tests were done using radioassay methods. The levels of thyroxine (T4), triiodothyronine (T3), thyroxine-binding protein (BT4) and thyrotrophic hormone (TSH) were determined simultaneously in the serum. In 4 myasthenics the levels of T3 and T4 were determined after administration of exogenous TSH (Ambinon). The control group comprised 13 subjects without thyroid function disturbances. The investigations demonstrated a statistically significant decrease of T4 (at p less than 0.05) and T3 (at p less than 0.01) in myasthenia as compared with the control group. Administration of TSH raised the T3 level by 40% and that of T4 by 6%. The results obtained by the authors indicate presence of secondary hypothyroidism in myasthenia possibly due, to failure of the hypophyseo-hypothalamic system.


[Diagnosis of bacterial infections of the urinary tract].

The aetiopathogenesis of bacterial infections of the urinary ways and the techniques used to isolate and identify the bacteria present in the urine are considered. The following aspects are covered: 1) Introduction (Clinical microbiology); 2) Urine and bacterial multiplication; 3) Diagnostic techniques in urinary way infections; 4) Urine leucocyte count; 5) Urine bacteria count; 6) Guidelines for applying bacteriological research; 7) Recurrent infections of the urinary ways; 8) Diagnosis of the site of infection; 9) Bacterial indentification and incidence.


[Pseudotumoral progression in a case of periosteal ossification of the femur].

A case of  periosteal ossification of the femur in a 14-yr-old boy is reported. The clinical, radiological and scintiscan pictures illustrated marked pseudotumoral lesions in a subject with a mild form of osteopsathyrosis.


Frequent coexistence of ocular malformations in externally malformed human fetuses.

60 undamaged human fetuses with some types of external malformations were taken from the human embryo and fetus collection at the Department of Anatomy, Kyoto University. They were examined macroscopically and stereo-microscopically for ocular and other external and internal malformations. 18 cases, that is 30% of the group, showed ocular malformations of the following type: approximated eyes (2 cases), approximated eyes + microcornea (1), microphthalmia (8), microcornea (3), corneal opacity (1), transparent sclera (2), antimongoloid obliquity of the palpebral fissure (1). In addition, asymmetric insertion site of the recti muscle(s) which can be regarded as a minor deviation, was found in 10 cases (16.7%). Other types of malformations were found simultaneously in a variety of organ systems and regions. No particular maternal factors were suggested to be related to such coexisting ocular malformations.


Collagen xenografts for bone replacement: the effects of aldehyde-induced cross-linking on degradation rate.

Collagen was extracted with acid from fresh calf skin, reconstituted and crosslinked with one of four aldehydes, and implanted into surgically created defects in rabbit mandibles. All grafts were histocompatible, with no signs of infection or rejection. There was partial degradation of simple aldehyde cross-linked collagen grafts, with new bone formation evident throughout as early as 4 weeks and complete by 3 to 4 months. The greater the degree of aldehyde-induced cross-linking, the longer the time of degradation, with dialdehyde-fixed specimens not starting to degrade for 6 months and highly cross-linked grafts intact and stable after 1 year. In grafted animals the mandible regained its original contour, while in control animals a defect remained after 1 year.


Obliterated pulp cavities in the Sanfilippo syndrome (mucopolysaccharidosis III).

Generalized obliteration of the pulp chambers and canals by irregular secondary dentin was observed in an individual with the Sanfilippo syndrome. Heretofore unreported, this dental finding may represent a manifestation of this mucopolysaccharide disorder.


Comparative study on the composition of the organic matrix of the long bones of the "normal" rat and of the mutant Op/Orl.

The organic matrix of the long bones of the "normal" rat strain and of its mutant Op/Orl were investigated. This latter strain exhibits some anomalles similar to Albers-Schönberg disease as well as tooth retentions. Bones (tibia, femur) were incubated with 14C-glucose and also submitted to a fractional extraction procedure (EDTA, urea) to separate soluble and insoluble fractions. The proteins, hexoses, hexosamines, hydroxyproline content of these fractions was determined as well as the radioactivity of the soluble extracts Glycosaminoglycans were also studied by cellogel electrophoresis after pronase digestion of the EDTA-extracts. Male and female animals of each strain were studied separately. The relative amount of soluble proteins (EDTA + urea extracts) was the same in both strains, the mineral content of the final residue was however higher in the mutant Op/Orl strain. The hydroxyproline content of the mutant-extracts were lower than in the original strain suggesting a lower soluble collagen content. This may be due to a faster polymerisation, insolubillisation of freshly synthesised collagen. The hexosamine content of the mutant urea extracts and the final residue was higher than that found in the analogous extracts obtained from the normal "normal" strain, suggesting a higher proportion of structural glycoproteins in the mutant bone, uronic acid being low or absent. Some other parameters were identical between the mutant and original strains but differed between males and females. The radioactivity of the soluble extracts was higher in the males than in females. The glycosaminoglycans of the EDTA extracts are also different: male-extracts show two bands on cellogel electrophoresis, one corresponding to chondroitin-sulphate, the other to hyaluronate. Females showed only the chondroitin sulphate band. The aminoacid composition of the insoluble residue of males was higher in basic amino acids (lysine, histidine, arginine) than the female extracts. These results indicate the existence of discrete well defined differences between the organic matrix of the orginal and mutant strain on one side and between male and female bones on the other side.


A comparison of fasting plasma insulin and growth hormone concentrations in marasmic, kwashiorkor, marasmic-kwashiorkor and underweight children.

Fasting plasma insulin and growth hormone concentrations were measured in 24 marasmic, 11 kwashiorkor, 16 marasmic-kwashiorkor, and 4 underweight children. Hormone measurements were made by a special modification of the Hales and Randle double antibody immunoassay with increased sensitivity in the concentration range 0-25 micronU/ml. Fasting plasma insulin was low in marasmus, kwashiorkor, and marasmic-kwashiorkor children, and increased to normal levels after recovery. Fasting plasma growth hormone was elevated in all groups during malnutrition and was significantly decreased to normal levels after recovery. There were no significant differences in plasma insulin or growth hormone levels between the different clinical types of severe protein energy malnutrition. These hormonal changes in severe protein energy malnutrition are of complex and not fully understood etiology. However, recovered children appear to have a hormonal pattern similar to that described in normal control infants and children.


The use of a crystalline amino acid mixture for parenteral nutrition in low-birth-weight infants.

Thirty-six preterm, sick, low-birth-weight neonates were given either total or partial parenteral nutrition. The patients were divided into three groups according to their birth weights: group A -less than 1,000 gm, 12 patients: group B--between 1,000 and 1,500 gm, 15 patients: group C--more than 1,500 gm, 9 patients. The solution for total parenteral nutrition contained 20% glucose and 2.6% crystalline amino acids plus appropriate amounts of vitamins and minerals. The volume of infusate given was usually 125 ml/kg/day, but varied depending on the clinical condition of the patient; occasionally it was as high as 150 to 175 ml/kg/day. Infusate of one-half strength was administered initially; its concentrations of glucose and amino acids were increased to three quarters and full strength gradually, if tolerated. The solution for total parenteral nutrition was infused into the superior vena cava via a central venous catheter; that for partial parenteral nutrition was given into a peripheral vein to supplement inadequate oral feedings. The period of parenteral nutrition lasted from 5 to 49 days, with an average of 13.2 days. The intake of 500 mg of nitrogen as crystalline amino acids and 100 kcal as glucose was capable of achieving body weight gain. Positive nitrogen balance of various degrees was also observed. Hyperglycemia of a slight to moderate degree was observed in nine patients; only three required insulin therapy. Two patients had thrombotic occlusion of the central venous catheter. The conclusion was reached that total parenteral nutrition or partial parenteral nutrition, when properly managed, is a safe procedure in small, premature infants. The amino acid solution given as a nitrogen source along with adequate calories was effective in promoting weight gain and nitrogen balance; it was apparently well tolerated by low-birth-weight neonates.


Low-dose intravenous insulin infusion versus subcutaneous insulin injection: a controlled comparative study of diabetic ketoacidosis.

Fourteen paients, 5 to 17 years old, with 18 episodes of uncomplicated diabetic ketoacidosis were randomly allocated and studied prospectively. The study group received 0.1 units of insulin per kilogram of body weight per hour as a continuous intravenous infusion; the control group received insulin subcutaneously. In both groups, a gradual fall in serum glucose and ketone levels was achieved. Serum ketones persisted longer in the intravenous group. No complications were encountered. The study suggests that both regimens of insulin administration are equally effective, but a low-dose constant infusion may provide more simplified and controlled management than the standard subcutaneous regimen.


Effectiveness of atrial pacing in Macaca mulatta as a function of pacing pulse intensity: modification by atropine and propranolol.

The functional relationship between heart rate, under atrial pacing, and the intensity of pacing pulses, was determined for intensities ranging from well below the complete heart rate capture threshold to suprathreshold intensities. A separate capture-intensity function was determined for each of the pacing frequencies 180, 240, 300 and 360 pulses per min, and then used to evaluate the effects of propranolol hydrochloride and atropine sulfate on atrial pacing. Propranolol resulted in an increase in the amount of current (mA) required to  achieve a given degree of cardiac capture, whereas atropine resulted in a decrease. These shifts in the capture-intensity functions along the intensity axis were possibly caused by drug antagonism of beta-adrenergic and cholinergic receptors, respectively, although the effects might also have been due to modifications of the electrical responsivity of the cardiac muscle, independently of the neural blockade.


Production of fetal asphyxia by maternal psychological stress.

Several lines of evidence indicate that maternal psychological stress leads to adverse pregnancy outcome in rhesus monkey. Chronic anxiety causes an increased stillbirth rate, fetal growth retardation, and altered placental morphology. On another time scale, lightening of maternal anesthesia during surgery produces an impaired fetal oxygenation while re-institution of anesthesia ameliorates the fetal asphyxia. The present study, for the first time, demonstrates a relationship between specific episodes of meternal psychological stress and exacerbation of fetal asphyxia in utero. Eight term pregnant rhesus monkeys were anesthetized with sodium pentobarbital. Catheters were placed both into the maternal and the fetal femoral arteries for the continuous recording of blood pressure and heart rate and for the intermittent campling of maternal and fetal blood. An open-ended catheter recorded intrauterine pressures. Following a complete repair, the anesthesia of the mothers was allowed to lighten. As the mothers awakened, the fetuses invariably showed the developemnt of fetal asphyxia. A fetal acidosis developed and the fetal oxygenation and repair of acidosis. Studies while the mothers were fully awake showed the repeated and regular development of episodes of heightened fetal asphyxia produced by episodes of stressful stimulation of the mothers. Episodes of maternal psychological stress led to changes in both fetal vital signs and blood chemical findings. These alterations in fetal state regularly followed the onset of the episodes of psychological stress by 50 seconds. These changes also usually remitted 50 seconds following the termination of the periods of stress. These results demonstrated a direct and unequivocal relationship between meternal psychological stress and fetal asphyxia. It is assumed the maternal stress produces impairments in the circulation to the uterus through an increased sympathetic nervous system activity and a shunting of the maternal blood-flow from the abdominal viscera to other organs as occurs in the fight-orflight reaction.


Organochlorine pesticide and polychlorinated biphenyl residues in selected fauna from a New Jersey salt marsh--1967 vs. 1973.

More than a half million pounds of DDT were applied to control mosquitoes in salt marsh estuaries of Cape May County, New Jersey, from 1946 to 1966. The use of DDT was discontinued in the County after 1966. In 1967, mean concentrations of DDT and metabolites ranged from 0.63 to 9.05 ppm in aquatic fauna, but by 1973 mean residue levels had decreased 84 to 99 percent among nine species. DDE was still present at reduced levels in nearly all samples in 1973, but other DDT isomers had mostly disappeared. Dieldrin was detected only in clapper rails, and residue levels decreased during the period. Mean concentrations of PCB's increased in the clapper rail, remained the same in the fiddler crab and mud snail, and decreased in the sheepshead minnow, mummichog, striped killifish, and salt marsh snail. Small amounts of mirex, toxaphene, cis-chlordane (and/or trans-nonachlor), oxychlordane, and HCB were detected in a few specimens.


[Clinical and biological manifestations following the interruption of prolonged treatment with clonidine].

In 7 out of 14 patients there were marked subjective symptoms following the interruption of prolonged treatment with clonidine. A significant increase in blood pressure, systolic and diastolic, heart rate and urinary catecholamine excretion was seen in the majority of cases. The clinical and biological manifestations would appear to reflect a phenomenon of derepression of sympathetic activity: the increase in urinary catecholamines is the biological result. The findings are of practical importance since they indicate that the interruption of anti-hypertensive therapy with clonidine must be under taken with caution, i.e. progressively.


[Anatomic and bacteriological study of surgically extracted valves in patients with bacterial endocarditis].

We studied 64 cases of bacterial endocarditis which required heart surgery for hemodynamic defects and/or failure of the antibiotic therapy. We performed a bacteriologic and histologic investigation of the removed valves. The organisms were evidenced through culture and specific stainings. According to the different organisms we evaluated the best duration of antibiotic therapy to achieved sterilization, and suggest a helpful medical and surgical treatment for the bacterial endocarditis.


Management of asthma. 2. Antiasthmatic drugs.

Asthma is a complex disease characterized by hyperreactive airways, with a wide spectrum of severity and presentation. Management requires confirmation of the diagnosis; characterization of the severity, chronicity, and precipitating factors; and development of an appropriate treatment plan based on the established efficacy of the various pharmacologic and nonpharmacologic modes of therapy. For acute symptoms, treatment with sympathomimetic amines appears to be the most appropriate initial measure. Corticosteroids are the most potent drugs available for dealing with acute symptoms that are unresponsive to bronchodilators. For the control of chronic asthma, either theophylline or cromolyn can be used initially. Chronic therapy may also require corticosteroids, in which case toxic effects of long-term therapy can be minimized by use of alternate-day dosage of prednisone or daily inhalation of beclomethasone dipropionate. Concurrent with drug therapy, environmental control measures can be used to minimize exposure to avoidable precipitants, and injection therapy with allergenic extracts can be considered if inhalant allergy can be convincingly demonstrated to play a major role. Failure of airway obstruction to respond to corticosteroids and the other measures should raise serious questions regarding the diagnosis.


Paravertebral and peripheral ligamentous ossification: an unusual association of hypoparathyroidism.

A 62-year-old man with idiopathic hypoparathyroidism and extensive paravertebral and ligamentous ossification is reported. The clinical and radiological findings of this, and other reported cases, are discussed and compared with other causes of paravertebral ossification.


Studies on pyrazine derivatives. Part VII. Synthesis and tuberculostatic activity of some pyrazine amidines and amidoximes.

In the reaction of 2-cyano-6-alkylaminopyrazines with sec. amines in the presence of anhyd. AlCl3 amidines 1-13 were obtained. From pyrazine-2-imidoesters, 2-cyano-pyrazines and pyrazine-2-carbothioamides and hydroxylamine, amidoximes 14-49 were easily prepared. These new compounds were, however, of little tuberculostatic activity (MIC between 31.5-2000 mug/cm3).


Derivatives of 4(7)-methyl- and 5,6-dimethyl-benzimidazolyl-2-mercaptoacetic acids.

Esters, hydrazides and hydrazones of the in title mentioned acids were prepared and screened for tuberculostatic activity. The strongest activity (MIC at 15-6 mug/cm3) was shown by hydrazide 4 and its hydrazone 4a.


Purification of 3-hydroxy-3-methylglutaryl-coenzyme A reductase from rat liver.

A procedure for the purification of 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating); EC 1.1.1.34] solubilized from rat liver microsomes is reported. This enzyme has a specific activity of 9,000-10,000 nmol of mevalonate formed per min/mg of protein. This represents a 4100-fold purification over the activity in microsomes, and a specific activity that is approximately 20-fold greater than the highest previously reported value. The enzyme is judged to be homogeneous on the basis of sodium dodecyl sulfate/polyacrylamide disc gel electrophoresis, polyacrylamide disc gel electrophoresis, and immunoanalysis. Data are also presented that indicate the separation of enzymatically active and inactive species of 3-hydroxy-3-methylglutaryl-coenzyme A reductase on affinity chromatography on a coenzyme A column.


Membrane fusion: studies with a calcium-sensitive dye, arsenazo III, in liposomes.

Fusion between vesicles, cells, or organelles may be defined as confluence of two membrane-bound compartments without access of their solutes to external milieu. To study fusion by this criterion, we have trapped the metallochromic calcium-sensitive dye, arsenazo III (AIII), partially calcium-saturated (AIII-Ca) in one population of liposomes (phoshatidylcholine 90:dicetylphosphate 10), and ethylene glycol-bis(beta-aminoethyl ether)-N,N'-tetraacetate (EGTA) in a second. In such mixtures, interaction of EGTA with AIII-Ca was measured by a large color shift from blue leads to red (decreased absorbance at 660 nm). Fusion of liposomes (but also lysis and diffusion across the membranes) was proportional to these decrements. The exogenous "fusogens," lysolecithin and retinol, were added to liposomes for 5-24 hr at 37 degrees; after rechromatography, measurements were made of total dye, fraction of dye converted from AIII-Ca to AIII, and total lipid. After correction for lysis and diffusion, lysolecithin (200 microng/ml) induced 23% fusion (volume of AIII liposomes confluent with EGTA liposomes) and retinol (300 microng/ml) induced 15%. With one molar percent cortisol (a membrane stabilizer) in the liposome membranes, fusion induced by fusogens was reduced 2-fold. Neither multi-nor unilamellar liposomes fused with each other in the absence of exogenous fusogens, despite wide variations in molar lipid ratios. Results suggest that liposome-liposome fusion is a slow process requiring exogenous fusogens, which may depend upon contributions of other membrane constituents to mimic closely the fusion of natural membranes.


Molecular composition of cyanobacterial phycobilisomes.

Phycobilisomes isolated from eight different species of cyanobacteria contain in addition to the light-harvesting phycobiliproteins, a small number of colorless polypeptides with molecular weights higher than those of the  chromopolypeptide subunits of the phycobiliproteins. In the phycobilisomes of the species examined, from four to nine colorless polypeptides were resolved by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Those of highest molecular weight (70,000-120,000) also occurred in the washed membrane fraction of the cell and may therefore be derived from the thylakoids, to which the phycobilisomes are attached in vivo. Colorless polypeptides of lesser molecular weight (30,000-70,000) appeared to be specific constituents of the phycobilisome. In strains of cyanobacteria that adapt chromatically, their synthesis, like that of the major phycobiliproteins, is regulated by light quality.


Replication and expression of plasmids from Staphylococcus aureus in Bacillus subtilis.

One S. aureus plasmid coding for tetracycline resistance, pT127, and four plasmids (pC194, pC221, pC223, and pUB112) coding for chloramphenicol resistance have been introduced by transformation into B, subtilis. The plasmids replicate in--and confer antibiotic resistance upon--their new host. These experiments show that the potential for genetic exchange between diverse bacterial species is greater than has been commonly assumed.


Self-administration of codeine plus acetylsalicylic acid in rhesus monkeys with unlimited access to the drugs.

The reinforcing effects of codeine (5.0 mcg/kg/infusion), acetylsalicylic acid (ASA) (2500 mcg/kg/infusion) and those of combinations of codeine (50 mcg/kg/infusion) plus (2500 or 10,000 mcg/kg/infusion) were studied in four groups of drug naive rhesus monkeys. Responding was engendered and maintained by infusions of 50 mcg/kg of codeine; maximal number of daily infusions being 500 to 1000. Infusions of 2500 mcg/kg of ASA plus 50 mcg/kg of codeine per infusion initiated responding from the 9th to the 10th day of the drug period on. The number of self-administered infusions did not exceed 200 daily. Monkeys self administered codeine without signs of intoxication. All three monkeys self-administering the combination of 50 mcg/kg of codeine plus 2500 mcg/kg of ASA died during the experiment. They exhibited signs of severe intoxication. A combination of 50 mcg/kg of codeine and 10,000 mcg/kg of ASA was not self-administered until the 12th day of the drug period. Two out of three monkeys initiated responding for the combination during the drug period. The number of self-administered infusions did not exceed 50 per day. A third monkey did not initiate self-administration during the 14 day drug period. Both monkeys which engendered self-administration died on the 14th day of the experiment as a result of general intoxication. These experiments suggest that even toxic doses of ASA will not prevent monkeys from self-administration when offered together with a positive reinforcing drug such as codeine under a schedule of continuous self-administration.


Reinforcing properties of intravenous procaine in rhesus monkeys.

The lever pressing behavior of rhesus monkeys was maintained by a fixed ratio 10 schedule of intravenous cocaine (3 monkeys) or codeine (2 monkeys) injections during 2 hour sessions. Saline or various doses of procaine hydrochloride were substituted for the baseline reinforcer for 6 consecutive sessions. Each substitution was separated by 3 or more days of cocaine or codeine reinforced responding. At one or more doses, procaine substitution resulted in response rates higher than saline control in all 5 animals. High response rates (greater than 30 injections per session) were obtained in 4 of the 5 monkeys. In addition, procaine self-administration was studied in two naive monkeys given 23 hour per day access to procaine following an initial 10 days of saline contingent operant level responding. At a dose of 0.3 mg/kg/injection, both animals initiated responding for procaine reinforcement. Drug intake varied widely from day to day, however each animal took over 1200 injections per day (over 360 mg/kg) at least once during the 30 days of access. With the exception of decreased food intake, there was little evidence for behavioral toxicity from these doses. Following a second 10 days of saline self-administration, both animals were given access to 3.0 mg/kg/injection procaine. A substantially greater intake of procaine was observed which was associated with marked toxicity.


A survey of a long-stay psychiatric population: implications for community services.

Two hundred and twenty long-stay psychiatric patients were surveyed by means of semi-standardized interviews and by obtaining information from nursing staff and case records. Each patient's needs for accommodation and employment were assessed as if immediate discharge from hospital were being contemplated. The results of the exercise emphasize the need for long-stay to permanent accommodation. The validity of this method of assessing community care requirements is discussed.


The hypothalamus and protein metabolism in rats.

Using the technique of mechanical isolation of the medial hypothalamus from the rest of the CNS, it has been concluded--based on total serum protein content, protein fractions as well as total serum amino acids--that under resting conditions the hypothalamic influence upon protein metabolism is achieved through the control exerted upon endocrine system rather than by a direct neural mechanism. The authors' results show that aminoacidemia is not a determining factor in feeding behaviour.


The role of the sodium, potassium, magnesium and calcium ions in the transfer of bioenergy, and the possibility of their substitution by other cations.

According to a previously presented model, two sodium ions and one calcium ion form an electric polarizing system of the diverging type, which favours the breaking of the high-energy bond of the ATP molecule, while two potassium ions and one magnesium ion form an electric polarizing system of the converging type, which helps the rebuilding of the high-energy bond of the ATP molecule. The condition required by one of the above-mentioned ions to be replaced with another type of ion (belonging to the same subgroup in Mendeleev's Table) capable of having a similar physiologic function is that the substitute ion be included in the same model of electric polarization (convergent or divergent) as the substituted ion. The electrocardiogram and mechanogram of the isolated frog heart were observed. The heart was perfused with a modifier Ringer solution in which some of the normal component ions were replaced with other ions belonging to the same principal subgroup in Mandeleev's Table. The necessary condition provided by the model for two ions of different types to have a resemblance in their physiological activity was confirmed by the results of the experimental data.


Angiotensin I-like immunoreactive substance in pineal gland of normal and Brattleboro rats with hereditary diabetes insipidus.

An angiotensin I-like immunoreactive substance (AI) was evidenced by a radioimmunoassay technique in the rat brain. The concentration of AI was significantly greater in the pineal tissue as compared to the hypothalamic or cerebral cortex tissue (p less than 0.001); its concentration was also higher in the pineal of the homozygous rats with hereditary diabetes insipidus (Brattleboro strain) as compared to the same tissue of the normal rats (p less than 0.001). The possible role of a pineal angiotensin system in the hydrosaline regulation is discussed.


Study of cardiovascular and auditory pathophysiological implications in a group of operatives working in noisy industrial surroundings.

One third of 160 operatives working in a permanently noisy industrial environment, within the range of 63-8000 Hz and intensity of sound of about 100 db, were found to suffer from a syndrome of neurocirculatory asthenia and 8.1% from arterial hypertension. Study of the ECG according to the criteria of the Minnesota code showed an increased frequency of upward deflection of ST segment (index 9-2) in 20.6% of the cases, depression of the ST segment with an ascending orientation in 50.62% of the cases and left ventricular hypertrophy (index 3-1 and 3-3) in 20% of the cases. Audiometry revealed loss of hearing at frequencies of 4000 CS in 16.1% of the cases. The results obtained suggest that the detrimental effects are not restricted only to hearing, but also that the alterations detected might evolve towards organic cardiac disorders.


Reflex and neuro-humoral pressor action of the hypertonic solutions.

The intraarterial injections of 50% urea or 20% NaCl induced a rise of the systemic arterial blood pressure simultaneously with a constriction of the vessels of the legs. The mechanism which is responsible for these phenomena is very complex. It includes a reflex arising from the arterial wall, which is mediated through the spinal cord, the release of catecholamines and of some still nonidentified pressor substances and a central component which is normally masked by the depressor sinus reflex.


Myelography with metrizamide.

Metrizamide (Amipaque) is a new water-soluble contrast medium for myelography. It differs from the conventional contrast media in that, because of its lower toxicity, it can be used also for cervical and thoracic myelography. The method of examination in myelography with water-soluble contrast media differs in some respects from that in myelography with oil-soluble contrast media. For the thoracic region, tomography is highly recommendable. After a description of the method of examination used, some examples of the abnormalities found are presented.


The complications of full-pelvic irradiation with particular emphasis to external beam therapy.

62 Patients with uterine carcinoma of cervix treated with high-dose large-volume full-pelvic irradiation given through co-axial-opposing pair portals over the anterior and posterior pelvis. Of these patients, 29 also received a single course of intracavitary radium supplementary to external beam irradiation. Only the severe complications which required surgical intervention have been analyzed, In the group of 33 patients who received only external irradiation, 4 developed such complications (12.1%).The overall incidence of those complications was about 19.3%. It is concluded that the treatment with hidh-dose large-volume full-pelvic irradiation technique, utilizing two opposing parallel pelvic portals, carries an incidence of morbidity 3-4 times the acceptable level and should be discouraged. Alternative techniques are discussed.


Hodgkin's disease: multidisciplinary contributions to the conquest of a neoplasm. Erskine memorial lecture, 1976.

In the 150 years since the first description of Hodgkin's disease, treatment methods have become increasingly sophisticated and effective. We now know that relapses are concentrated within the first five years after treatment. Accordingly, anyone who survives the first five years has a 95% chance of cure. Modern techniques in diagnosis, staging, and combined chemotherapy and irradiation have brought us within sight of total therapeutic conquest of this once inexorably fatal malady.


Experimental production of arachnoiditis with water-soluble myelographic media.

After myelography with either metrizamide (300mg l/ml) or meglumine iocarmate (280 mg l/ml), mild to severe arachnoid fibrosis was demonstrated radiographically and histologically in primates. Intrathecal injections of metrizamide (170 mg l/ml) or autologous cerebrospinal fluid produced less arachnoiditis. The risk of arachnoiditis is probably minimized by the use of reduced volumes and concentrations of water-soluble media. Controlled studies of arachnoiditis following myelography are probably more reliable in the primate model  than in other experimental animals.


Utilization of a high energy photon beam for whole body irradiation.

Use of a high energy linear accelerator (giving high dose rates) for whole body irradiation is recommended because (a) there is a shorter treatment time compared with other techniques using orthovoltage or 60Co irradiation; and (b) there is more comfort for the patient, who does not have to turn over to receive an acceptably uniform dose. Dosimetry indicates that the usual data is not applicable for such treatments given at large distances from the source. A method of dosage calculation at large distances was checked by using TLD dosimetry in a Rando phantom.


A comprehensive study of LiF TL response to high energy photons and electrons.

Effects of beam quality, cavity size, TLD state, and medium on the response of thermoluminescent dosimeters were studied. LiF TL-700 powder, extruded rods, and ribbons were irradiated with Co-60 gamma rays, 4, 6, 8, 33, and 45 -MV x rays, and 3, 5, 10, 15, 20, 25, 30, 35, 40, and 45-MeV electrons. Relative TL responses were assessed in water and Lucite, and the results compared. The results of this study were compared with those of previously published studies, and certain discrepancies resolved.


Localization of fresh experimental venous thrombi in rabbits using 99mTc-oxine-labeled autologous platelets.

99MTc-oxine-labeled autologous platelets were used to visualize fresh experimental venous thrombi in rabbits. Clots were formed by intravenous injection of suspended 1.3 micron iron particles while a magnet was positioned over a vein proximal to the injection site. Thrombi formed prior to and following platelet injection were visualized well.


Single port technique of mantle field treatment in Hodgkin's disease using very high energy x-ray beams.

Treatment pd irradiation of Hodgkin's disease is described indicating the advantage of this energy range and the appropriate dose build-up modifications necessary to achieve a single port irradiation technique.


Metabolism of thromboxane B2 in the cynomolgus monkey.

[5,6,8,9,11,12,14,15-3H8]-Thromboxane B2 was injected into the saphenous vein of female cynomolgus monkeys, and blood samples were withdrawn from the contralateral saphenous vein. The compound was eliminated from the circulation with a half-life of about 10 min after an initial rapid disappearance. Some more polar products appeared with time, and also small amounts of material less polar than thromboxane B2; however, the dominating compound in all blood samples was unconverted thromboxane B2. About 45% of the given dose of tritium was excreted into urine in 48 hrs. Several metabolites of thromboxane B2 were found. The major urinary metabolite was identified as dinorthromboxane B2 (about 32% of urinary radioactivity). Unconverted thromboxane B2 was also found in considerable amounts (13% of urinary radioactivity). It is concluded that 1) dehydrogenation at C-12 is not a major pathway in the degradation of this compound, in contrast to metabolism at the corresponding C-15 alcohol group of prostaglandins; 2) after having gained access to the circulation, thromboxane B2 is the main circulating compound; however, assay of thromboxane B2 in plasma will be complicated or precluded by large artifactual production of the compound by platelets during sample collection.


Identification of the major urinary metabolite of thromboxane B2 in the monkey.

Thromboxane B2 (TxB2) was biosynthesized from prostaglandin endoperoxides (PGG2, PGH2) using guinea pig lung microsomes and infused into an unanesthetized monkey. Urine was collected and TxB2 metabolites were isolated by reversed phase partition chromatography and high performance liquid chromatography. A major metabolite (TxB2-M) was found to be excreted in greater than two-fold abundance relative to other metabolites. Its structure was determined by gas chromatography-mass spectrometry to be dinor-thromboxane B2. In vitro incubation of TxB2 with rat liver mitochondria yielded a C18 derivative with a mass spectrum identical to that of TxB2-M, substantiating that the major urinary metabolite of TxB2 in the monkey is a product of a single step of beta-oxidation.


Lack of covalent modification of prostaglandin synthetase (cyclo-oxygenase) by indomethacin.

We have previously shown that aspirin irreversibly inhibits prostaglandin synthetase (cyclo-oxygenase) by acetylating the active site of the enzyme. By utilizing 14C-labeled indomethacin and a close analogue, we now show that indomethacin, unlike aspirin, does not covalently modify cyclo-oxygenase. Furthermore, indomethacin binding to the enzyme may be reversible since even though indomethacin can inhibit acetylation by aspirin, when enzyme inhibited by indomethacin (1 micronM) is treated with 200 micronM aspirin 3 times for 1 hour each, complete acetylation of cyclo-oxygenase is achieved.


Effects of 19-hydroxy-prostaglandins on oviductal and uterine motility.

The effects of 19-hydroxyprostaglandins (19-OH-PGs) were tested in vivo on the rabbit oviduct and uterus and on the rhesus monkey (Macaca mulatta) uterus. The 19-OH-PGEs suppressed spontaneous oviductal and uterine activity in the rabbit. The qualitative effect on the rabbit oviduct of 19-OH-PGEs was similar to that of PGE2. However, the typical response of the rabbit uterus to PGE2 was an increase in muscle activity. With regard to the rabbit oviduct, 19(R)-OH-PGE2 was as potent as PGE2, but 19(S)-OH-PGE2 was approximately 1/2 as potent as PGE2. Based on the dose of 19-OH-PGEs usually required to cause a minimal suppression and the dose of PGE2 required to cause a minimal stimulation of rabbit uterine activity, 19(R)-OH-PGE2 was twice as potent as PGE2 while 19(S)-OH-PGE2 was 1/2 as potent as PGE2. Stimulatory effects on the rabbit oviduct and uterus were observed following administration of 19-OH-PGFs and PGF2alpha. The potency on the rabbit oviduct of 19(S)-OH-PGF2alpha was about 1/5 to 1/10 that of PGF2alpha; the potency of 19(R)-OH-PGF2alpha was about 1/10 to 1/20 that of PGF2alpha. Both 19-OH-PGFs were approximately 1/5 to 1/10 as potent as PGF2alpha on the rabbit uterus. At the doses tested 19-OH-PGFs were inactive on the monkey uterus. Thus, these compounds are at least 1/5 as active as PGF2alpha. In contrast, 19(R)-OH-PGE2 had approximately the same potency as PGE2 in stimulating monkey uterine activity; but 19(S)-OH-PGE2 was approximately 1/3 as potent as PGE2.


[Some aspects of biliary secretion in four species of primates (P. mandrillus, P. papio, E. patas and M. mulatta) (author's transl)].

Effect of several factors on flow and composition of bile of four species of Primates has been studied. Flow of bile widely varied. The smallest flow was found in E. patas and the greatest in P. mandrillus; P. papio and M. mulatta flows were intermediate. Cholic acid concentration in basal bile was small. Electrolites Na+, K+ and C1- were found in concentration close to its plasmatic values. In all four species, interruption of enterohepatic circulation of bile salt, induced a clear decrease in basal flow. Secretin injection (1 U/kg) induced flow increases in P. mandrillus. In M. mulatta and E. patas relationship between logarithm of secretin doses and biliary responses seems to occur. Cholecistokinine-Pancreozimine (2 U/kg) produced in P papio espectacular increases of flow and bile salts concentration with concomitant chloride decreases. Vagal stimulation gave no clear results, although vagal section and use of parasimpathicolitic drugs induced bile flow decreases that show a possible tonic vagal action on extrahepathic biliary tree.


The effects of IgG2 and of antigen concentration on prozoning in the complement fixation test for bovine brucellosis.

Addition of Brucella-specific IgG2 to solutions of Brucella-specific IgG1 initially induced prozoning and at higher concentrations prevented all reaction in the complement fixation test (CFT) for bovine brucellosis. Some infected cattle may be diagnosed as brucellosis-free due to a high ratio of specific IgG2 to IgG1. Increasing the concentration of antigen in the CFT reduced the tendency to prozone.


The glycosaminoglycan content of the liver in bovine GM1 gangliosidosis.

Chemical analysis of the livers from four calves with GM1 gangliosidosis was negative for significantly elevated levels of glycosaminoglycans. The chemical findings confirmed morphological studies in which hepatic changes were minimal or absent. The findings were compared with the published evidence for the hepatic storage of glycosaminoglycans in human GM1 gangliosidosis.


[Diverticula of the stomach - diagnosis of their importance (author's transl)].

Gastric diverticula may be due to dilatation or traction. 75% are found in the fundus, 15% in the prepyloric antrum. In 10% they were situated elsewhere. Symptoms are unspecific. Radiography has to be combined with endoscopic investigation of their nature. Smaller diverticula are mainly treated conservatively, the larger ones will require surgery because of chronic symptoms and complications.


[Irradiation pneumonitis after high voltage treatment of carcinoma of the breast (author's transl)].

Pulmonary changes following irradiation after post-operative high voltage therapy of the carcinoma of the breast is usually greater than following orthovoltage treatment. Among our own 635 patients, treated post-operatively with telecobalt including the chestwall, pneumonitis occurred in 35%. The data published in the literature and our own show the need for refined techniques of irradiation and individual planning.


[The influence of quality of irradiation on survival in inoperable bronchial carcinoma (author's transl)].

Irradiation of inoperable bronchial carcinoma with constant ortho-volt technique has worse results than with mobile irradiation, since the individual dosage in several fields can be raised without damaging the skin. With mega-voltage limits of skin tolerance, changed absorption or protection of healthy tissues are absent, so that it is easier to deliver doses affective on the tumor. Survival-rates can be related to dosage. During the first few years similar doses of mega-voltage lead to more frequent survival. In part such results depend on differences in standard dosage with the various techniques. More important for the worse results of orthovoltage treatment are the higher doses, the greater volume of irradiation and scatter which may cause greater damage to immunity. 5 years survival of patients with a central inoperable bronchial carcinoma is hardly altered but during the first 2-3 years megavolt therapy is clearly more effective.


Pseudomonas aeruginosa infection in cystic fibrosis. Diagnostic and prognostic significance of Pseudomonas aeruginosa precipitins determined by means of crossed immunoelectrophoresis.

A total of 133 patients with cystic fibrosis have been followed for up to 5 years with monthly examinations including bacteriological examinations of sputum. Sera from the patients were examined by means of crossed immunoelectrophoresis for the occurence and number of precipitating antibody specificites against Pseudomonas aeruginosa. Poor prognosis in cystic fibrosis was associated with chronic colonization (9 months - more than 5 years) of the respiratory tract with mucoid Pseudomonas aeruginosa, and with an onset of the chronic colonization before puberty. Among the patients with chronic Pseudomonas aeruginosa colonization, poor prognosis was associated with high numbers of precipitins against antigens from these bacteria (up to 61). The number of Pseudomonas aeruginosa precipitins increased on an average with five per year in chronically colonized patients. Rapidly increasing number of precipitins was associated with poor prognosis. Patients with any degree of impairment of the ventilatory function and any changes on the chest radiographs could contract chronic Pseudomonas aeruginosa colonization. Poor ventilatory function and severe changes on the chest radiographs was associated with high numbers of Pseudomonas aeruginosa precipitins and with poor prognosis. Although many O groups of Pseudomonas aeruginosa were found in the chronically colonized group of patients, 53% of the patients harboured strains belonging to O group 3 or 3/9, and the highest numbers of precipitins were found in serum from these patients.


[Clinical findings and conservative therapy in diverticular disease of the colon].

Diverticular disease of the colon can be divided into 1) a prediverticular state similar to spastic colon syndrome, 2) colon diverticulosis without symptoms, 3) chronic symptomatic diverticular disease with pain and stool irregularities and possible attacks with acute colicky pain and 4) acute diverticular disease with possible obstruction, fistula, and perforation and also bleeding. A diet rich in plant fibers is indicated in spastic colon syndrome, chronic diverticular disease and in patients after attacks of acute diverticular disease. A conservative and waiting policy is also indicated in acute diverticulitis and in bleeding.


[Effect of orally administered pancreatic extract on Vibrio cholerae infection during protein deficiency].

Two groups of 5 and 6 Vervet monkeys respectively were fed a protein-free diet. Both groups of protein depleted Vervets developed a minor decrease of serum and intestinal immunoglobulins, as well as marked impairment of exocrine pancreatic function. Thereafter the groups were challenged with Vibrio cholerae, while one group received purified pancreatic extract by oral administration. The group without pancreatic extract developed severe and significantly longer lasting diarrhea than the group with pancreatic extract. Vibrios were excreted for much longer in the former group. It is concluded that exocrine pancreatic function is involved in the local defence mechanism against cholera during protein deficiency.


Spinal neurons project to the dorsal column nuclei of rhesus monkeys.

Cells of origin of ascending nonprimary afferents to the dorsal column nuclei of rhesus monkeys have been identified in the spinal cord by the retrograde transport of horseradish peroxidase. These neurons are mainly located in lamina IV and medially in more ventral laminae of the dorsal horn on the side ipsilateral to the medullary injection. Large neurons in the ventral horn ("spinal border cells") also appear to project to the ipsilateral dorsal medulla. The dorsal column nuclei of a primate thus are the recipient not only of ascending dorsal root fibers but also of a more complexly integrated spinal input.


Thyrotropin-releasing hormone: stimulation of colonic activity following intracerebroventricular administration.

Intraventricularly administered thyrotropin-releasing hormone in rabbits elicited an increase in intraluminal pressure changes, a response commonly associated with muscular activity of the colon. The response appears to be central in origin with peripheral expression relying primarily on cholinergic receptors.


Latent form of Scrapie virus: a new factor in slow-virus disease.

Scrapie is an unusual slow-virus disease of sheep which is very much like kuru and Creutzfeldt-Jakob disease, both fatal, slow neuological diseases of man. In mice, scrapie usually has an incubation period of about 6 months. Intraperitoneal inoculation of virus particles into newborn mice caused no disease, and there was no detectable virus replication for 1 year, but high titers of scrapie were present in the spleen and brain at 18 months. Virus replication occurred in mice injected from 4 days after birth by all inoculation routes, wheter or not they were injected with scrapie virus on day 0. The results suggest that scrapie virus replicates peripherally only in thymocytes, which are not present in mice until a few days after birth. The latent state suggests that the comparable human diseases could appear in later life as a result of perinatal infection. In some respects these diseases resemble premature senility.


Aldehyde oxidase compartmentalization in Drosophila melanogaster wing imaginal disks.

Distribution of the enzyme aldehyde oxidase in mature Drosophilia melanogaster wing disks may allow visualization of known developmental compartments comprising (i) presumptive dorsal and ventral wing surfaces, and (ii) the presumptive anterior wing and the presumptive posterior wing.


Covalent labeling of the tetrodotoxin receptor in excitable membranes.

A photoaffinity labeling technique is described by which a tetrodotoxin analog is covalently bound to receptor sites associated with the sodium pores of excitable membranes. The biological activity of the toxin analog is retained after the covalent binding reaction.


GM2 ganglioside lysosomal storage disease in cats with beta-hexosaminidase deficiency.

Two kitteens with progressive neurologic disease had increased concentrations of GM2 ganglioside in their cerebral cortex. Examination under the light microscope revealed cytoplasmic vacuolation of neurons and hepatocytes. Transmission and scanning electron microscopy demosntrated cytoplasmic inclusions encompassed by membranes in various central nervous system cell types and in hepatocytes. Beta-D-N-acetyl-hexosaminidase activity was reduced to about 1.0 percent of normal in brain, liver, and cultured skin fibroblasts of the diseased kittens; both major electrophoretic forms, A and B, of the enzyme were deficient. In fibroblasts from the parents of the diseased kittens, this enzyme activity was intermediate between that of affected and normal cats, suggesting an autosomal recessive mode of inheritance of the enzyme defect. Histopahtological and ultrastructural lesions, glycolipid storage, enzyme defect, and pattern of inheritance are similar to those of human GM2 gangliosidosis type 2.


Genetic rescue of a lethal "null" activity allele of 6-phosphogluconate dehydrogenase in Drosophila melanogaster.

While a null activity mutant allele of the structural gene for 6-phosphogluconate dehydrogenase in Drosophila melanogaster is lethal, a similar mutation for glucose-6-phosphate dehydrogenase is not. Double mutant combinations lacking both enzyme activities, obtained either by recombination or by mutagen treatment of a chromosome bearing the lethal allele, result in a restoration of viability. The indispensability of the pentose phosphate shunt in Drosophila appears to depend upon the specific position of the block within the pathway.


The clinical efficacy and cost analysis of cranial computed tomography and the radionuclide brain scan.

Cranial computed tomography (CCT) has already been demonstrated to provide significant diagnostic information in patients with neurologic disease and to reduce the need for special neuroradiologic procedures. The important question remaining is: Should CCT replace the radionuclide brain scan (RBS) as the first diagnostic study in most patients with suspected intracranial pathology? Data are now available to define the costs and benefits of this substitution. The technical costs of CCT have been determined by a national survey and have shown to be $130 per patient at a volume of 50 patients per week. The costs of RBS at the Mallinckrodt Institute have been estimated at $51 per patient. Data from the literature indicate that CCT is slightly more sensitive and considerably more accurate than RBS. Eighteen to twenty-eight percent of patients studied by CCT and RBS have abnormalities (e.g. cerebral atrophy and ventricular dilatation) that are only detected by CCT, and the overall accuracy of CCT is 95%, while the accuracy of RBS is approximately 70%. Substituting CCT for RBS is cost-beneficial. Although CCT is more costly, it increases overall accuracy by approximately 25%. The cost benefit is further increased by the reduction of complicated diagnostic procedures (and associated hospitalization and morbidity) and improvement in diagnostic information for the individual patient. Substituting CCT for RBS may not be more costly because a positive RBS will be followed by CCT (because of increased diagnostic information), and a negative RBS may be followed by CCT (because of increased accuracy), whereas a positive or negative CCT is unlikely to be followed by RBS.


Unusual fractures during convulsions in two patients with renal osteodystrophy.

Two men undergoing chronic hemodialysis sustained unusual fractures during grand mal convulsions. Both patients showed radiologic evidence of renal osteodystrophy. In one, the fractures involved both femoral necks. In the other, a comminuted fracture occurred in the inferior portion of the left scapula.


Treatment of rheumatoid arthritis with gold.

There have been three important double-blind studies evaluating the use of gold therapy in rheumatoid arthritis. Patients treated with gold have decreased number of joints with synovitis, decreased ring size, increased grip strength, and roentgenographic evidence of arrest or decrease in the progression of skeletal lesions. If a patient with active synovitis does not respond to nonsteroidal anti-inflammatory drugs after four months of treatment, he is a candidate for gold therapy. Maintenance gold therapy has been shown to sustain clinical improvement. Patients must be monitored with appropiate laboratory tests.


Chronic radiation enteritis complicating non-Hodgkin's lymphoma.

A case of radiation enteritis in a patient with non-Hodgkin's lymphoma is described. The patient's complaints suggested recurrence of her lymphoma and radiographic studies were nondiagnostic of radiation-induced enteritis, delaying diagnosis and appropriate therapy. An inadvertent error in radiotherapy technic and fibrous adhesions resulting from the staging laparotomy contributed to the radiation injury. Radiation enteritis is a rare complication of irradiation of abdominal lymphoma, but it must be considered by physicians who encounter a similar situation.


The economics of caring for the aged.

Certain aspects of the economics of caring for the aged in South Africa are considered. The few years before an accelerated growth rate of the population in South Africa takes place should be used to prepare the economic and other resources of the country. The increasing per capita income of the non-White population should supply the resources to meet the needs of its aged. The use of various accommodations facilities is reviewed. Guidance of medical and paramedical experts, who are specially trained to care for the aged, is needed.


Experimental pulmonary nocardiosis in monkeys.

The study describes an easy and reproducible technique of producing pulmonary nocardiosis in monkeys, yielding consistent morbidity and mortality results. Introduction of the fungal suspension into the lower canaliculus, with or without debridement of the canalicular epithelium, produced fatal pneumonitis in 1-2 weeks. Specificity of the lesions was determined by demonstration of Nocardia in tissue sections and in culture.


Identification and purification of the specific antigen of Paracoccidioides brasiliensis responsible for immunoelectrophoretic band E.

A new purified antigen (E2) of Paracoccidioides brasiliensis mycelial growth phase was isolated by immunoadsorption from a crude metabolic soluble extract of the fungus. The antiserum prepared in a rabbit by inoculation of E2 antigen developed only one immunodiffusion line with the crude metabolic extract. Findings on immunological analysis showed that E2 antigen is the antigenic component of immunoelectrophoretic band E. The isolated antigens did not possess detectable alkaline phosphatase activity. It reacted in immunodiffusion tests with all the sera (14/14) from P. brasiliensis infected patients containing precipitating antibodies.