[Types of sensitivity (author's transl)]. Pathogen-host relationships are interactions which, on the part of the host, in contrast to in vitro infections not only depend on the available substrate but require a specific sensitivity to the individual pathogen. According to the species of the pathogen, the host responds with either a local or generalized sensitivity. Whereas local sensitivity persists throughout life, a generalized sensitivity is changed to a local sensitivity after the initial manifestation, by the development of a general immunity. Phylogenetic arguments support the assumption that sensitivity and its differences are genetically determined.


[Cephalexin levels in the bronchial secretion of children (author's transl)]. Cephalexin serum levels and its content in bronchial secretions have been studied in six children with pneumonia or chronic bronchitis following a single oral doses of 30 to 50 mug/kg body weight. The cephalexin content in bronchial secretions reached values between 0,47 and 2,3 mug/ml (on average 0,84 mug/ml). The percentage of the cephalexin content in bronchial secretions varied from 4,3 to 133 percent (on average 22,6%) as compared to the corresponding serum levels.


[Health and disease. Critical thoughts on the health concept of the World Health Organisation (WHO) (author's transl)]. In recent times, health politics has crystallized more and more into a independent branch of social politics. Health as well as disease, have become a central topic of public and individual discussion. A elucidation of the relevant concepts seems to be urgently required. The article, starting from the well-known WHO definition of health, attempts a critical discussion of the concepts of "health" and "disease". It becomes apparent that, according to the present state of knowledge, neither can be conclusively defined, by either medical or psychic scientific methods. The material is subjected rather to a constant change decisively dependent on psychic currents at the time in question.


[Prognosis of occupational bronchial asthma after change of occupation and elimination of antigen (author's transl)]. In order to eliminate the antigen, 168 patients with metal dust allergy made a complete change of occupation, The number of those who were rehabilitated after change of occupation was in inverse proportion to the duration of exposure to the antigen. Subjects with persistent bronchial asthma showed an increase in the complaints which corresponded to the antigen exposure. So as to be able to detect secondary developments deriving from the allergic changes in the mucous membrane, a few parameters were examined after the change of occupation for their relationship to the duration of exposure. Such relationships were found for secondary inflammatory processes in the airways (detection of pathogenic organisms in the sputum, concomitant sinusitis and pleural residues from inflammatory processes). The duration of exposure to the antigen also affects the frequency of persistently increasing bronchospastic irritability after change of occupation.


[Success of physiotherapeutic interval training combined with standardized hemoderivative in intermittent claudication (author's transl)]. In a cross-over trial with 114 patients, intravenous Actovegin or an oral placebo were administered in addition to basic physiotherapy. In the evaluation 105 of the subjects were taken into consideration. It was shown that the test group (n = 53) achieved a 12% increase in walking distance (measured in the standardized walking distance test) compared with the placebo group (n = 52). The therapeutic success rate, i.e. the evaluation base for the efficacy of basic physiotherapy was comparatively good and statistically confirmed at 69.8% and 73.1% for the two groups. From this it may be concluded that basic physiotherapy can be effectively supported by Actovegin.


[Changes in the Conception of the Course of Tuberculosis: (author's transl)]. In our sphere of life the picture of tuberculosis has altered. Infections in children have become less severe and considerably rarer. The chronic tuberculosis of age is decreasing. The reasons for the change in the course of tuberculosis are to be found in an increasing power of resistance of the body produced by better social hygienic conditions, a better immunological defense and the institution of modern therapy. Tuberculosis should only be subdivided into primary and post-primary stages with the possibility of spreading through local progressiveness to lymphadenobronchogenic and hematogenic pathways.


[BCG Vaccination and Tuberculous Meningitis (author's transl)]. While BCG Vaccination of newborn infants has been carried out in North Germany for many years, in BadenWurttemberg and Bavaria it has only become standard practice in a few "islands" Nevertheless, tuberculosis, and especially tuberculosis of children, has regressed fairly uniformly in all the Federal States, as is shown by tuberculous meningitis, for example. In June 1975, the single modified serum used was withdrawn in the Federal Republic because of the increased complication rate. The point for discussion now is whether routine vaccination of the newborn should be started again as soon as a vaccine is available. Since the probability of a child falling ill with tuberculosis in the Republic nowadays is small and in addition the protection is not complete and of limited duration, the complications of the vaccination must be taken very seriously into consideration. But all children who are a high risk (e.g foreigners) should receive BCG vaccination in infancy even now.


[Fungal spore content of the air in Munich (author's transl)]. A volumetric determination of seasonal variations in the fungal spore content of the air was carried out with Andersen samplers (culture plates) in the center of the City of Munich and 2.4 km (1.5 miles) west of it. Cladosporium spores were predominant (60% altogether), followed by those of penicillium and aspergillus. Up to 22 different genera were counted among the varieties. The spores of cladosporium, penicillium, aspergillus, botrytis, thysanophora and epicoccum are twice as densely represented 2.4 km west of the center of the City than in the center. The most frequent types of spore during the course of the year are described.


[Safeguarding healthy living conditions-legal foundations of environmental hygiene (author's transl)]. The aim of environmental hygiene is to maintain or regain healthy living conditions for man, animals and plants. An important area of environmental hygienic effort is the safeguarding of health as a state of optimal physical, psychic and social well-being. Man has a right to a healthy environment to live in in the fullest sense. It should be protected by a great number of provisions relating to health in environmental law. Meaningful provisions require careful preparation as is shown by the example of residues in foodstuffs.


[Rationalization of infusion therapy (author's transl)]. Infusions are a principal cost factor for hospital dispensaries. The demands of modern infusion therapy are gone into from the point of view of the anesthesist. Opportunities for rationalization arise through producing them in the hospital dispensaries and their problems relating to GMP provisions are described. An alternative solution by reduction of the ready made supply from the industry is discussed.


[Benefits and dangers of sport for the postural and locomotor apparatus (author's transl)]. The possible prophylactic, rehabilitative and the, today often unjustly exaggerated harmful effects of sport on the locomotor apparatus are reviewed. Damage and dangers can be avoided if attention is paid to measured amounts appropriate to age, improved individual style of the type of sport practised, and to the biomechanical susceptibility of certain sections of our postural and locomotor apparatus due to recent developmental history.


[Advertising and safety in skiing (author's transl)]. Pertinent accident statistics show that, opposed to the need for safety which ought to be expected, there is an insufficiently practiced safety consciousness. The objective probability of getting into danger rises with the increasing readiness to take risks. Advertising tries to influence the potential customer quantitatively and qualitatively in such a way that he believes that his secret desires will be fulfilled by the acquisition and use of certain products. The mechanism of character transference through paralogical conclusions required for this shows parallels to the logic schizophrenia. Both sponsors and ad-men can contribute decisively to safety in skiing if they dispense with the use of certain attributes in their advertisements.


[Osteosynthesis and plastic surgery of the visceral cranium (author's transl)]. The conservative treatment of fractures of the visceral cranium and the base of the skull has become separated to an increasing extent from the earlier reconstructive measures of the facial surgeon. The skull is restored with due consideration for the anatomical function and cosmetic factors. Wire osteosynthesis, maxillary and mandibular splinting, fixing to the skeleton by Adam's clasp, reconstruction of soft parts, filling of skin defects precede the subsequent functional follow-up therapy. Exact diagnosis and interdisciplinary planning of treatment before the early intervention are of more value for the patient with a damaged skull than precipitate emergency measures under conditions of inadequate equipment and personnel. A plan of treatment from a background of 230 of our own cases is presented.


[Clinical aspects and therapy of extensor tendon avulsion in the distal phalanx of the finger (author's transl)]. Avulsion of the extensor tendon of the terminal phalanx of the finger is the most frequent form of all subcutaneous tendon ruptures. The rupture may occur in the tendinous part or cause a fracture of the bone in the region of the insertion. Healing requires at least 5-6 weeks conservative therapy with a Stack's splint being attempted first. Surgical fixation of the terminal joint with Kirschner wire should only be carried out in exceptional cases because of the risk of infection and damage to the joint. Operative union of the ends of the tendon is only immediately indicated with open tendon severance and in old injuries in which complete severing of the tendon can be recognized. If tendon regeneration is unsatisfactory, the Georg method of purse-string suture with temporary arthrodesis is recommended later.


[Conservative and operative treatment of fractures in the region of the elbow joint in childhood. Comparative study of the late results (author's transl)]. The serious complications following fractures in the region of the elbow joint are frequently avoidable by selection of adequate methods of treatment. The advantages of operative in comparison with semi-conservative methods of treatment are presented here in relation to our own patients.


[Anal and perianal complications of Crohn's disease (author's transl)]. Anal and perianal lesions in Crohn's disease such as fistulae, fissures, abscesses and proliferative ulcerous proctitis are often misinterpreted and consequently unsatisfactorily treated. They always indicate a florid intestinal attack or a relapse after previous intestinal resection. Out of 153 patients with Crohn's disease in the last 11 years we have had 59 cases (= 38.6%) with a history of anal changes or such changes were demonstrable on admission to hospital. Only after subtle diagnosis in which the nature and extent of these complications and the location of the intestinal disease focus are determined, the most promising therapy, after all possibilities of conservative treatment have been exhausted, is intestinal resection. Local surgical measures which would often endanger continence, are reserved for the individual case.


[Value of diagnostic measures in blunt epigastric trauma with particular reference to peritoneal lavage (author's transl)]. In 95 patients suffering blunt abdominal trauma the diagnostic validity of abdominal exploration, blood pressure, pulse rate, leukocyte count, and hemoglobin was compared with the results of peritoneal lavage for the detection of intra-abdominal bleeding. Classical clinical symptoms alone are not reliable in evaluation of the patient with abdominal trauma, especially if there are associated multiple injuries. Diagnostic peritoneal lavage has the highest accuracy (more than 95%) and an early diagnosis of intraperitoneal bleeding by widespread use of this method improves the prognosis in these patients.


[The placebo effect (author's transl)].

[The placebo effect (author's transl)]. Placebos are liable to affect most diseases, physiologically autonomic and emotional functions and types of performance and also to produce side effects. Types of reactions to placebos are highly dependent on suggestion. Tranquilizer properties are registered more frequently than those of stimulants, and placebos are taken for active drugs more often than vice versa. Type of application, personality of the therapist and intensity of the stress situation may potentiate or diminish the effects of placebos in a specific manner. Constancy of time and situation as a condition for the identification of a placebo reactor is demonstrable to a limited extent only.


[New aspects of the pathogenesis and therapy of alcoholic delirium (author's transl)]. Clinically, and especially biochemically, alcoholic delirium corresponds closely to an incipient but reversible exogenous hepatic coma. The blood levels of ammonia in particular, free phenols and lactate are greatly increased. These same metabolites increase slightly in the blood of persons with healthy livers after a single alcohol loading. The treatment of alcoholic delirium consists of optimal sedation with Distraneurin, which appears to have no side effects on the liver. There is even a lowering of the raised lactate level in the blood after a single administration of Distraneurin. Ammonia and phenols are reduced by ammonia-lowering aminoacids, lactulose and bifidum milk. Most important, however, is strict abstention from alcohol, which alone brings about a rapid improvement of pathological biochemical and morphological liver findings.


[Thalassemia minor in families of German descent in the Bergische Land (author's transl)]. Heterozygous classical beta-thalassemia was found in 13 subjects of pure German descent, 11 of them from the Bergische Land (NW Germany) during the past three years. Clinically it became manifest in a moderate degree of anemia with marked hypochromia and reduced mean corpuscular volume. The number of red blood corpuscles and the value for serum iron were ascertained to be in the upper limits of normal or raised. The diagnosis of Mediterranean anemia was confirmed by hemoglobin electrophoresis with a rise in HbA2 of more than 3%. A slight increase in HbF may also occur. The importance of genetic counseling of thalassemia patients is emphasized. The occurrence of thalassemia even in pure German populations must be increasingly reckoned with.


[The determination of calcitonin for hospital use (author's transl)]. The significance of measuring calcitonin by biological and radioimmunological methods for diagnostic and therapeutic purposes is demonstrated in 18 cases of medullary thyroid carcinoma (MTC). The radioimmunoassay used permits the differentiation between normals (up to 0.5 ng/ml) and patients with MTC (3 to 120 ng/ml). As clinical symptomatology is often unspecific (tumor of the neck, perhaps in combination with diarrhea), the determination of calcitonin proved to be a useful preoperative diagnostic tool which can be improved by calcitonin stimulation tests (pentagastrin i.v.). Calcitonin values provide information on the completeness of surgical procedures or the recurrence of the tumor before clinical symptoms are manifest.


[Serotonin and the dumping syndrome (author's transl)]. The serotonin level in patients after a 2/3 resection of the stomach (Billroth II) is normal to moderately raised. Patients with a dumping syndrome show no significantly different figures for the excretion of free serotonin in the 24-hr urine. The level of serotonin in patients after gastric operation is regulated to normal or slightly raised values by increased serotonin production in the gastrointestinal tract whether a dumping syndrome develops or not. Knowledge of the serotonin levels is consequently of therapeutic significance because a dumping syndrome may exist with and without raised serotonin values.


[Fine needle biopsy of cold goiter nodules (author's transl)]. Fine needle biopsy of hypofunctional, scintigraphically detected cold goiter nodules is being increasingly applied as a diagnostic method. Its diagnostic value is estimated by the results gained from 4,555 punctured patients, 1,076 of these nodules were histologically proven, and from the literature. The most important indication for the application of this method is a neoplastic lesion of the thyroid. 6.8% of 20,384 nodules were cytologically suspicious or malignant. Of 2,412 surgically controlled patients 85.5% were correctly diagnosed. Among 490 malignancies 92.1% were correctly diagnosed and 7.9% were false negatives.


[Results of a trial of a coronary therapeutic agent, Adalat (author's transl)]. This report concerns data on 54 patients with coronary heart disease. With a 4-6 week treatment with 3 X 1 capsule Adalat daily, the attacks of angina pectoris fell from 1-7 daily to 1-2 per week. In more than 50% of the subjects, no more attacks occurred. Nitroglycerine consumption fell accordingly. Ergometry carried out on 12 patients at the end of the study showed an increased load resistance of 20 to 30 W in each case, compared with the initial value. The preparation was well tolerated.


[Modern principles of incorporation of total dental prosthesis (author's transl)]. A promising therapy with total prostheses is only possible if it is possible to incorporate the prostheses into the functional processes of the oral cavity without disturbance and to coordinate it with the functions of the mandibular joint and the musculature. Overemphasis of a measure does not ensure success, only the cooperation of physical biomechanical, functional and psychic factors.


[Modern therapy of fractured jaws (author's transl)]. Modern treatment of fractured jaws includes the anatomical and functional restoration of the broken mandible and the middle part of the face. The central feature on the one hand, is the reposition and fixation of the fractured skeletal parts in the correct axial line, and on the other hand, occlusal rehabilitation, which is to be considered the criterion of a correct position for the dentigerous fragments. For this purpose, conservative and/or operative measures cone into question, according to the type of fracture and dislocation. The conservative methods enable reposition and fixation of fragments by means of dental fixation dressings. At the present time, wire suture and wire suspension which are always combined with conservative methods as well as plate osteosynthesis are to be mentioned as the most common operative procedures for fractures of the mandible and the middle part of the face.


Grafting in dentistry today (author's transl). Enossal grafts are common practice in dentistry. The prognosis of such grafts fluctuates between primary failure and 10 years, and is largely determined by the indication: the more accurate the indication, the better the prognosis! In partial diastemata in the lower jaw, satisfactory results for a longer time are to be expected if the concurrently blocked remaining denture is periodontally sound.


[Gingival grafts as therapeutic measures for periodontal diseases (author's transl)]. Gingival grafts represent an operative intervention within the sphere of periodontal surgery which enable a widening of fixed gingiva. Carried out as an outpatient operation, it troubles the patient little. Supported by the oral hygiene of the patient, it creates the necessary conditions for the progression of the periodontal disease to be stopped by local therapy in the region of the gingival pocket.


[The present position of cleft surgery (cheilognathopalatoschisis) (author's transl)]. The present state of cleft surgery enables optimal results to be obtained through operation appropriate to the tissue and development and a longterm treatment lasting until the end of growth. The great individual variation in the clefts demands from the operator exact knowledge of the atypical tissue formations and mastery of the most varied plastic surgical possibilities.


[Allergic reactions to dental materials (author's transl)]. Contact and distant reactions of an allergic nature to dental materials are rarer than is generally assumed. This is explained by the anatomical and physiological peculiarities of the oral mucous membrane and the chemical and physical properties of the materials. Clinical phenotypic allergic reactions due to prosthetic and filling materials are discussed and special problems of diagnosis and differential diagnosis are emphasized.


[Pattern of recurrence of surgically treated primary malignant melanomas of the skin. Therapeutic consequences (author's transl)]. Recurrences were observed within 2 years in 14 out of 169 operatively treated malignant melanomas of the skin (Stage I). Since it cannot be excluded that local remanifestation may be the starting point of proliferative metastasis formation, an extensive low-dose irradiation therapy limited to one day preoperatively is suggested, to prevent the appearance of prognostically unfavorable local recurrences of operatively treated malignant melanoma.


[A modified guaiac test for the early detection of tumors of the intestinal tract (author's transl)]. Of 1400 patients who were submitted to the Haemoccult test, 46 showed a postive result. Among other things there were 29 polyps, of which 3 already showed a focal carcinoma, and 5 carcinomata of the large intestine and 3 gastric carcinomata were also diagnosed. Over 70% of the tumor hosts had observed bleeding per anum at some time. In order to detect the number of false nagative results, patients were investigated in the same way even when the Haemoccult test had been negative three times. In this way 55 polyps were found as well as 7 partly advanced carcinomata of the large intestine. 35% of the Haemoccult-negative patients stated bleeding per anum in their history. The number of false negative findings must be considerably higher than previously estimated.


[Particular aspects of testicular tumor in the elderly (author's transl)]. Malignant testicular tumors mainly occur in early adult life. 14 (7.8%) of our 180 patients with testicular tumors, treated from 1966 to 1976, were between 50 to 68 years of age. The pathological anatomical classification showed 9 germinal and 5 non-germinal tumors. To find out which tumor classification is the best for prognostic information and assessment of therapeutic consequences, we recommend setting up a central testicular tumor panel and register and refer to the multilateral study already initiated.


[Cryptogenic liver abscess (author's transl)]. The successful treatment of two patients with cryptogenic liver abscess, a special type of pyogenic abscess, is reported. Quick diagnosis by methods which do not distress the patient, e. g. scintigraphy and echography, leads to a decisive improvement in the prognosis. Opinions are given on the differential diagnosis of cryptogenic, pyogenic and parasitic (amebic) liver abscesses. The good chances for treatment of cryptogenic abscesses compared with the secondary pyogenic liver abscesses are to be found not least in their usually solitary appearance. This is shown particularly clearly in the classification of the patients operated on for pyogenic liver abscess in our hospital in the last ten years into multiple and solitary liver abscess. As in the pyogenic abscess, so in the primary cyptogenic liver abscess is transperitoneal open drainage the method of choice for treatment.


Blastomycosis: specificity of antigens reflecting the mating types of Ajellomyces dermatitidis. In a study of sera from patients with proven or suspected blastomycosis, positive immunodiffusion tests were obtained in all active cases when fresh sera were tested with a cell sap (CS) antigen. False negatives occurred on occasion when an ethanol precipitate (EPF) antigen was used alone. No false positives were found. The CS antigen from the (+) mating type had in common two lines of identity with the (CS) antigen of the (-) type. In addition, other lines were present when the patient was infected with the same mating type as was used for the preparation of the antigen. No differences in the electrophoretic patterns of the enzymes leucine amino peptidase or phosphatase were noted when preparations from the two mating types were compared. However, a distinct pattern was noted when the alpha esterases of the (+) and (-) mating types were examined. Specific alpha esterase antibodies were present in patients' sera.


Clinical manifestations of chronic thiamine deficiency in rhesus monkey. In the course of multiple episodes of thiamine deficiency in the rhesus monkey, the triad of anorexia, apathy, and hind limb weakness is the earliest clinical manifestation. In later episodes, nystagmus, abducens paresis, midline ataxia, dysmetria, and congestive heart failure are also seen. With the exception of dysmetria, the neurologic signs promptly respond to thiamine administration. Pair-fed controls showed no clinical signs. Neither peripheral neuropathy nor edema was observed. Thiamine-deficiency in the experimental animals was confirmed by blood transketolase assays.


Genetic factors in childhood epilepsy with focal sharp waves. II. EEG findings in patients and siblings. Electroencephalographical investigations were performed in 203 epileptic children exhibiting focal sharp waves in the EEG and in 312 siblings. As controls served 685 brain-healthy children (Gerken 1971) as well as 252 children with spike wave absences and their 242 siblings (Doose et al. 1973). According to the EEG findings in probands so-called "centrencephalic" EEG-criteria (theta rhythms, spikes and waves, photosensitivity) as a symptom of a genetically determined seizure susceptibility can be expected in at least 60% of the probands. 18% of the siblings showed at least once one definite "centrencephalic" EEG pattern. These results must be regarded as minimal values, since in siblings only one electro-encephalographic study could be performed. The results make it evident, that in the pathogenesis of epilepsy with focal sharp waves a genetically determined seizure susceptibility plays a very important role. After comparison with the results of genetic investigations in patients with spike wave absences (Doose et al. 1973) the difference as for the genetic basis between "centrencephalic" and focal epilepsies apparently is only due to a different gene density.


Genetic factors in childhood epilepsy with focal sharp waves. I. Clinical data and familial morbidity for seizures. 203 epileptic children (127 boys, 76 girls), who had demonstrated at least once focal sharp waves in the EEG during the course were investigated regarding clinical and historical data as well as familial morbidity for seizures. Expectedly, the seizure symptomatology was multiform: focal seizures of different type, especially secondarily generalized, grand mal, psychomotor fits, infantile spasms etc. Organic brain lesions play an important role. In 23% of cases a familial seizure affliction can be registered. The morbidity (close family) is significantly lower than in families of patients with spike wave absences (2.5 and 4.4% resp., Doose et al. 1973). Like in spike wave absence epilepsies mothers and mothers' siblings are more often affected than fathers and fathers' siblings. Among the affected relatives grand mal epilepsies predominate. The increase of febrile convulsions and spike wave absences observed in the families of absence epileptics is not present. In probands with onset of epilepsy during early childhood a significantly increased familial affliction can be observed. A more extensive discussion of the results will follow in a second paper deeling with EEG findings in probands and siblings.


[Treatment of advanced breast cancer with alkylating agents]. The results obtained in 26 patients suffering from metastatic cancer of the breast no longer sensitive to hormone treatment are reported. The patients were treated with ciclophosphamide (CTX) (500 mg i.v.) once a week and triethylenethiophosphamide (20-30 mg i.m.) (TSPA) every 4 weeks associated with cyclophosphamide as follows: CTX--CTX--CTX--CTX+TSPA. 9 objective regressions (34.6%) were observed. Those with objective regression lived 28 months on average (SD 23.45) and those without lived on average 11.41 months (SD 9.89). The difference is statistically significant. Side effects of various types were observed in 7 patients (27%).


Levamisole and hamster pouch carcinogenesis. Seventy-five male and female Syrian hamsters (Cricetus auratus), 10 months of age, were studied for the effects of systemically administered levamisole upon the process of chemical carcinogenesis of buccal pouch mucosa. In twenty-five animals (Group II) the left buccal pouch was painted three times weekly with a 0.5 per cent solution of 9,10-dimethyl-1,2-benzanthracene (DMBA) in heavy mineral oil. After each topical application of carcinogen to the buccal pouch, animals in Group II received approximately 0.7 mg. of levamisole hydrochloride orally by means of a pipette. In another twenty-five animals (Group I) the left buccal pouch was painted three times weekly with DMBA, but they were not given levamisole. The twenty-five animals in Group III served as untreated controls. In those animals which received levamisole chemical carcinogenesis of the buccal pouch was retarded. Fewer tumors developed, and they were of smaller size.


Tissue response to silicone rubber when used as a root canal filling. To test the tissue compatibility of silicone rubber when it is used as a root canal filler, excess material was intentionally forced into the apical tissues in primates. The tissue response was one of general acceptance, with the usual response being fibrotic encapsulation. A low degree of inflammation was noted. Further studies are in progress.


Apical hard-tissue deposition in adult teeth of monkeys with use of calcium hydroxide. The anterior teeth of five adult monkeys were divided into two groups. In one group the pulps were removed and the teeth were left open to oral fluids. The other group had vital pulps. Five teeth were designated as controls. The pulp canals of both groups were debrided, filed, and flushed thoroughly. In the two experimental groups (vital and pulpless), the apical third of the canal was filled with Ca(OH)2. In the control group no medication was placed in the canal. The coronal access of the canals of all groups was sealed with amalgam. After 270 to 330 days, the teeth were sectioned and examined histologically. No apical bridging was observed in any group.


Interaction of nutrition and infection in clinical practice. Resistance to infection is determined by a great many interralted factors, but one of the most significant variables is nutritional status of the host. The interaction between nutrition and infection has been described as synergistic, with malnutrition reducing resistance to infection, and infection, in turn, negatively affecting nutritional status. There are qualitative if not quantitative similarities between the evidence that has been gathered from studies of children living in vast areas of the developing countries, in which high rates of both severe malnutrition and infectious diseases are linked with high mortality rates, and evidence from studies of disadvantages children living in the United States in economically depressed migrant camps, Indian reservations, or rural and urban poverty, or children compromised by debilitating chronic diseases. Maternal nutritional status during pregnancy must receive more attention as a factor in the newborn's resistance to infection. Intrauterine malnutrition may cause impaired cellular immune function in the small-for-date infant which persists throughout the first year of life. Further research is needed to clarify this relationship. The optimal management of infections includes management or maintenance of nutritional status, and, in turn, management of nutritional deficiencies include prevention and treatment of infections.


Energy metabolism of brain in human protein-calorie malnutrition. Cerebral blood flow (CBF) and carbohydrate metabolism were studied in 5 normal children and 25 children, aged 40 months or less, with varying degrees of protein-calorie malnutrition (PCM). CBF in normal children and those suffering from grade I PCM was 90.3 +/- 5.7 ml/100 g/min, a value comparable with that obtained by other investigators, but the proportion of glucose taken up by the brain which combined with oxygen, the oxygen/glucose index (OGI), was 65.8%, indicating significant conversion of glucose into lactic acid. Cerebral lactic acid production was 45.3 micronM/100 g/min, and the respiratory quotient (R.Q.) was 1.00. With increasing severity of PCM, there was increased glucose utilization and a progressive reduction in the OGI. In grade IV PCM, CBF was 68.7 +/- 5.4ml/100g/min, and the OGI was 34.7%. Cerebral lactic acid production was 27.4 micronM/100 g/min, and the R.Q. rose to 1.52. These findings suggest that in severe human PCM the proportion of glucose undergoing aerobic oxidation is reduced, and that in addition to being converted to lactic acid, a significant proportion of glucose is transformed by the brain into long chain fatty acids.


Fasting plasma levels of glucose, acetoacetate, D-beta-hydroxybutyrate, glycerol, and lactate in the baboon infant: correlation with cerebral uptake of substrates and oxygen. The energy-rich substrates available to the fasting stressed baboon neonate and infant are quantitatively similar to the metabolic fuels presented to the stressed low birth weight human newborn. Within a few hours after birth, fasting arterial plasma glucose levels in the baboon neonate approximate those of 4-6-week-old baboon infants after a 20-hr fast. Lactate levels are high and comparable for both age groups. In contrast, beta-hydroxybutyrate is quite low in the immediate neonatal period, but rises to significantly higher levels (P less than 0.001) after a fast at 4-6 weeks. In addition, glycerol levels are higher (P less than 0.02) in the fasted older infant compared with the fasting neonate. Computation of mean cerebral blood arteriovenous differences and oxygen equivalents for animals studied in the first 50 hr of life demonstrates that glucose uptake can account for 50% or less of cerebral oxygen consumption in the newborn period. In confirmation, the respiratory quotient in these animals is 0.52 +/- 0.06. Cerebral oxygen consumption in the immediate neonate is greater than can be explained by utilization of glucose and the small quantities of acetoacetate and beta-hydroxybutyrate available at this time. At birth, cerebral uptake of lactate is noted, but this phenomenon is not observed at 6 and 12 weeks of age.


Vesicoureteral reflux in the primate: II Maturation of the ureterovesical junction. Infant rhesus monkeys frequently show vesicoureteral reflux unlike adults. We studied monkeys born of mothers who had been on normal or protein-deficient diets. Protein deficiency may influence the time that reflux continues, but this was not statistically proved. Reflux disappears over time. The time was influenced by when the pregnancy was initiated and the maturity of the infant. Maturation as measured by skeletal maturity scores correlated well with the time of reflux, but growth as measured by birth weight did not. Vesicoureteral reflux in the monkey is frequent, but maturation of the ureterovesical junction occurs by age 3 years and reflux disappears.


Comparative labelling and biokinetic studies of 99mTc-EDTA(Sn) and 99mTc-DTPA(Sn). Gelchromatography column scanning has been used to study the fractions of 99mTc-pertechnetate, 99mTc-chelate and reduced hydrolyzed 99mTc in preparations  of 99mTc-EDTA(Sn) and 99mTc-DTPA(Sn). The labelling yield of 99mTc-EDTA(Sn) chelate was as high as 90--95% when 100 mumol EDTA-H4 and 0.5 mumol SnCl2 was incubated with 10 ml 99mTc-eluate for 30--60 min at room temperature. The study of the influence of the pH-value on the fraction of 99mTc-EDTA shows that pH 2.8--2.9 gave the best labelling yield. In a comparative study of the labelling kinetics of 99mTc-EDTA(Sn) and 99mTc-DTPA(SN) at different temperatures (7, 22 and 37degreesC),  no significant influence on the reduction step was found. The rate constant for complex formation, however, increased more rapidly with increased temperature for 99mTc-DTPA(Sn). At room temperature only a few minutes was required to achieve a high labelling yield with 99mTc-DTPA(Sn) whereas about 60 min was required for 99mTc-EDTA(Sn). Comparative biokinetic studies in rabbits showed that the maximum activity in kidneys is achieved after 12 min with 99mTc-EDTA(Sn) but already after 6 min with 99mTc-DTPA(Sn). The long-term disappearance of 99mTc-DTPA(Sn) from the kidneys is about five times faster than that for 99mTc-EDTA(Sn).


The patient with peripheral arterial occulsive disease. Peripheral arterial occlusive disease predominantly involves the lower extremities. The greatest incidence occurs in males over 50 years of age. Manifestations include intermittent claudication, diminished or absent pulsations, pallor, and trophic changes. Patients are particularly vulnerable to infection, ulcer formation, and gangrene. The treatment program aims to promote circulation, and to prevent tissue damage and complications. Some patients have reconstructive surgery, which includes prosthetic grafts as well as bypass procedures.


Immune thrombocytopenic purpura: an overview. Idiopathic thrombocytopenia is one of the most common hematologic disorders. It has many causes, most of which precipitate an immunologic reaction that results in immune thrombocytopenic purpura. A systematic approach to diagnosis and therapy is important.


Neutropenia: when and when not to treat. When the number of neutrophils is substantially lower than normal or their function is impaired, the patient is at increased risk of infection. Antibiotic therapy is indicated only when infection is apparent.


Investigations into the relationship between structure and function of diphtheria toxin. Studies on the structure-function relationship of diphtheria toxin are reported. New methods are described for the preparation of pure intact ("unnicked") toxin and for the preparation of the individual A and B chains. A biological assay method for the B chain is also presented, as well as a method for the labelling of "nicked" (one peptide bond broken) diphtheria toxin with 131I such that the label is confined to only one of the two polypeptide chains. Alterations of diphtheria toxin with specific reagents reveal that modifications of the tryptophan, methionine, and arginine residues did not result in a significant loss in toxicity, whereas treatment of the toxin with omicron-phthalaldehyde or by photooxidation with rose bengal results in a complete loss of the toxic activity. Modification of tyrosine by iodination results in active toxin, whereas modification by tetranitromethane causes a loss in activity. Preliminary results also indicate that the isolated A chain is about an order of magnitude more active in incorporating adenosine diphosphoribose into translocase (elongation factor 2) than whole or nicked toxin is under identical conditions. The observed structural properties are discussed in view of the functional activity of diphtheria toxin in cell-free systems as well as in cell cultures. Evidence is presented indicating that the B chain binds to membranes: it inhibits the action of nicked toxin on HeLa cells.


Microcomplement fixation studies on the evolution of alpha-glycerophosphate dehydrogenase within the genus Drosophila. Antisera were prepared against purified alpha-glycerophosphate dehydrogenase (EC 1.1.1.8) (alphaGPDH) from Drosophila melanogaster, D. virilis, and D. busckii. The immunological distances between the enzymes from the 3 species and those from 31 additional drosophilid species agree in general with the accepted phylogeny of the genus. These data permit an estimate that the subgenus Sophophora diverged 52 million years ago from the line leading to the subgenus Drosophila. The antiserum against melanogaster alphaGPDH was capable of distinguishing allelic variants of alphaGPDH. On the basis of presumed single amino acid substitutions, no drosophilid alphaGPDH tested differed from the melanogaster enzyme by more than eight or nine substitutions. The study was extended to include representatives of six other dipteran families. The immunological distances between alphaGPDH from Drosophila and alphaGPDH from these dipterans were reasonably consistent with a phylogeny of the order Diptera established by more conventional means. The unit evolutionary period of this enzyme was estimated to be 18 million years.


Amino acid sequence of the NH2-terminal extra piece segments of the precursors of mouse immunoglobulin lambda1-type and kappa-type light chains. The mRNA molecules coding for mouse immunoglobulin light (L) chains direct the cell-free synthesis of precursors in which extra peptide segments precede the amino termini of the mature proteins. The results of amino acid sequence analyses of two precursors labeled with 20 radioactive amino acids enabled unambiguous determination of the complete primary structure of the extra piece segments. The complete sequences (and sizes) of the NH2-terminal extra pieces are: in MOPC-104E lambda1 L-chain precursor, Met-Ala-Trp-Ile-Ser-Leu-Ile-Leu-Ser-Leu-Leu-Ala-Leu-Ser-Ser-Gly-Ala-Ile-Ser (19 residues); in MOPC-41 kappa L-chain precursor, Met-Asp-Met-Arg-Ala-Pro-Ala-Gln-Ile-Phe-Gly-Phe-Leu-Leu-Leu-Leu-Phe-Pro-Gly-Thr-Arg-Cys (22 residues). The extra pieces in the precursors of MOPC-104E (lambda1), MOPC-41 (kappa), and MOPC-321 (kappa) L-chains differ extensively from each other in their amino acid sequence (65-73%). In addition to this sequence heterogeneity, the extra pieces are characterized by a high percentage of hydrophobic residues: 69% in the MOPC-104E lambda1 L-chain precursor (this report), 73-75% in the kappa L-chain precursors [Schechter, I. & Burstein, Y. (1976) Proc, Natl. Acad. Sci. USA 73, 3273-3277]. The marked hydrophobicity of the extra piece suggests that it may favor interaction of the precursor with cell membranes, in a manner similar to the function of the "hydrophobic domain" of membrane-bound proteins. We propose two possible targets for interaction: (i) the endoplasmic membranes, where the NH2-terminal extra piece is cleaved from the precursor to yield mature protein destined for secretion; (ii) the cell surface membrane, where the intact precursor is anchored by virtue of the hydrophobic extra piece to serve as the antigen-recognizing receptor.


Isolation of the penicillin-binding peptide from D-alanine carboxypeptidase of Bacillus subtilis. The D-alanine carboxypeptidase of B. subtilis is a membrane-bound enzyme which is inhibited by penicillins and binds them covalently. The enzyme has been labeled with [14C]- or [35S]penicillin. After tryptic or Pronase digestion of the labeled, denatured, reduced, and carboxymethylated enzyme, a radioactive peptide was isolated in each case. The amino acid compositions of these two peptides are reported. The Pronase peptide was a subset of the tryptic peptide. Neither contained a cysteine residue and the only amino acid in the Pronase peptide to which the penicillin could be bound was a serine residue.


180 degrees rotation of ciliary rows and its morphogenetic implications in Tetrahymena pyriformis. With quasi-surgical techniques, longitudinal somatic ciliary rows in Tetrahymena pyriformis have been rotated 180 degrees. New structures formed in the rotated ciliary rows during growth and reproduction are disposed 180 degrees opposite to their normal positions or orientations, confirming the earlier findings of Beisson and Sonneborn on Paramecium. However, during cell fission the rotated ciliary rows exhibit abnormality in orientation along the fission zone; the configuration of these rows near the anterior end of the posterior product of fission is consequently affected. Rotated ciliary rows have been employed as a tool in the analysis of morphogenetic problems: (a) The contractile vacuole pore is normally located on the left side of a ciliary row; but it is on the right of inverted rows. Hence, the morphogenetic properties of the two sides of the ciliary row associated with the contractile vacuole pore are different and this difference is the sole determinative factor as to the side of the ciliary row on which the contractile vacuole pore is located. (b) The process that generates the rotated ciliary rows frequently also brings about the implantation of an extra band of longitudinal microtubules at a specific site on the cell surface. This extra structure is inheritable, which opens up opportunities for the study of microtubular assembly in vivo.


Studies on the control of development: isolation of Bacillus subtilis mutants blocked early in sporulation and defective in synthesis of highly phosphorylated nucleotides. To test our model on the mechanism of initiation of differentiation in Bacillus subtilis, we tested early blocked (stage 0) sporulation mutants for their ability to synthesize highly phosphorylated nucleotides. We also isolated early blocked asporogenous mutants with the aid of the intercalating drug tilorone. Among all mutants tested we found that the spo0F-bearing strain was unable to synthesize adenosine 3'(2')-triphosphate 5'-triphosphate, pppAppp. A revertant of this mutant regained the ability to both sporulate and synthesize pppAppp. Ribosomes of the asporogenous mutant isolated at T2 (2 hr after the end of logarithmic growth) of sporulation, in contrast to the wild type, do not synthesize adenosine 3'(2')-diphosphate 5'-diphosphate, ppApp, or adenosine 3'(2')-diphosphate 5'-triphosphate, pppApp, but synthesize guanosine 3'(2')-diphosphate 5'-diphosphate, ppGpp, and guanosine 3'(2')-diphosphate 5'-triphosphate, pppGpp. This behavior is characteristic of ribosomes from vegetative, not sporulating, cells. Ribosomes from the sporogenous revertant behave like those of the wild type. The results suggest that the spo0F mutation may be a mutation in the structural gene for pppAppp synthetase. The inability to synthesize pppAppp in this strain also prevents the formation of "sporulation-specific ribosomes," i.e., ribosomes that synthetize ppApp and pppApp. The present experiments suggest that the nucleotide pppAppp participates in the initiation of sporulation by triggering a sequencies of events required for the production of heat-resistant spores.


Partial amino-acid sequences of human and rabbit C-reactive proteins: homology with immunoglobulins and histocompatibility antigens. Partial amino-acid sequence analyses of the amino terminus of rabbit C-reactive protein and of a peptide isolated from human C-reactive protein after cyanogen bromide cleavage show an extensive sequence homology between these proteins. Computer analysis detected a distant but significant homology between rabbit C-reactive protein and the CH3 domain of human IgG, In addition, an examination of the limited data available for the amino-acid sequences of human and mouse histocompatibility antigens revealed a similarity between these proteins and C-reactive protein and, therefore, immunoglobulins; These relationships are presented as evidence in support of the hypothesis that C-reactive protein and immunoglobulins share, in addition to functional similarities, a common evolutionary origin with the major histocompatibility antigens.


Purification of a carbonic anhydrase from the inner ear of the guinea pig. A soluble carbonic anhydrase (carbonate hydro-lyase, EC 4.2.1.1) has been purified to homogeneity from the membranous lateral wall (stria vascularis, spiral ligament, spiral prominence, and outer sulcus) of the guinea-pig inner ear. About 1% of the protein of the membranous lateral wall is carbonic anhydrase. The specific activity of the enzyme in homogenates of the lateral wall is 1.6-1.8 times that of whole blood; for homogenates of the components, stria vascularis and the fraction containing the spiral ligament, the specific activities are 0.9 and 2.0 times the specific activity of whole blood, respectively. No other cochlear fraction examined contains appreciable carbonic anhydrase. The purified enzyme has a molecular weight of about 30,000, a specific activity 60--80% that of carbonic anhydrase C from blood, and an electrophoretic mobility similar to that of the blood enzyme. Cochlear carbonic anhydrase is half-maximally inhibited by 4 X 10(-9) M acetazolamide, is completely inhibited above 10(-5)M acetazolamide, and forms a fluorescent complex with 5-dimethylaminonaphthalene-1-sulfonamide, by which it can be distinguished on polyacrylamide gels. This report describes both another isolation of a carbonic anhydrase from a source other than blood and the isolation of an inner-ear enzyme.


Thyrotropin-releasing hormone: physiological concomitants of behavioral excitation. Two doses (10 microng and 100 microng) of thyrotropin-releasing hormone (TRH) or saline were injected intraventricularly in rabbits pretreated with either saline, pentobarbital or phenobarbital. Behavior, EEG patterns, respiration rate and heart rate were monitored for 100 min posttreatment. TRH significantly altered all physiological indices except heart rate in both barbiturate- and saline-pretreated animals. The results support the contention that TRH modified central functioning by direct action. Results are discussed in terms of barbiturate antagonism and excitatory effects of TRH.


An investigation of nalorphine and perphenazine as negative reinforcers in an escape paradigm. Rhesus monkeys were trained to self-administer morphine intravenously at dose levels sufficient to develop physical dependence. The monkeys were then trained to press a lever to escape a continuous infusion of the morphine antagonist, nalorphine. When saline was substituted for the nalorphine, escape responding extinguished. After morphine self-administration was eliminated, responding to escape from nalorphine was maintained in the postdependent monkeys, showing no difference from escape responding during morphine dependence. Finally, perphenazine was substituted for the nalorphine and the monkeys reliably escaped continuous infusions of this phenothiazine. The escape procedure appears useful for analyzing the aversive properties of drugs.


Sudden toxicity of methadone in monkeys: behavioral and electrophysiological evidence. A sudden and potentially lethal toxic reaction to a previously well-tolerated maintenance dose of methadone occurred in 4 of 6 monkeys. The reaction was characterized by gross behavioral and respiratory depression and a marked attenuation of both early and late components of the visual evoked response with an increase in most latencies. The nature of the evoked response alteration suggests a widespread central nervous system depressant effect of the drug during toxicity. Concomitant with the toxic reactions were dramatic increases in plasma methadone concentrations. Therefore the observed changes in sensitivity to methadone would appear to be the consequence of a sudden shift in pharmacokinetics resulting in toxic plasma concentrations.


Results from tattooing port-wine hemangiomas. A long-term follow-up. Nineteen patients who had completed their course of dermatattoo treatment for the camouflage of port-wine hemangioma were evaluated at an average of 3.1 years following completion of treatment. A panel of 7 people evaluated preoperative and postoperative photographs and judged that none of the patients were more than "50 percent improved" in the camouflaging of their hemangioma, and that most of them (15 out of 19) were either "not improved" or "25 percent improved," as compared to their original photographs. We cannot rule out the possibility that this treatment may be effective in adults, as all of our patients at the time of their first treatment were between the ages of 4 and 20 years; and most of them were between 6 and 10 years old. On the basis of this evaluation, we no longer recommend the technique of dermatattoo for camouflage of port-wine hemangioma in patients in the younger age group.


Neurochemical characterization of a new potent and selective serotonin uptake inhibitor: Lu 10-171. The neurochemical characteristics of a new bicyclic phthalane derivative-Lu10-171 [1-(3-(dimethylamino)propyl)-1-(p-fluorophenyl)-5-phthalancarbonitrile; citalopram]-have been investigated. Lu 10-171 and its metabolites were compared with tricyclic thymoleptics in several tests for serotonin (5-HT),noradrenaline (NA), and dopamine (DA) uptake inhibiton in vitro and in vivo. Lu 10-171 is a very potent and completely selective inhibitor of the 5-HT reuptake mechanism, being 2-10 times as active as chlorimipramine. The metabolites of Lu 10-171 show weak 5-HT uptake inhibiting properties. Lu10-171 and its metabolites are devoid of NA uptake inhibiting properties and in this respect they clearly differ from the tricyclic antidepressants, which posses effects both on 5-HT and NA uptake. The inhibition of 5-HT uptake in vitro is competitive and not connected with an increased efflux of 5-HT. Lu10-171 and its metabolites only inhibit DA uptake in extremely high concentrations and in this respect they are even weaker than chlorimipramine and other tricyclic thymoleptics. Like the tricycle thymoleptics, Lu 10-171 is without effect on MAO and does not change the endogenous levels of brain monoamines. Due to the selective action on 5-HT uptake, Lu 10-171 seems to be a valuable tool in studying the role of central 5-HT neurone systems in experimental neuropharmacology as well as in the ethiology of depressive illness.


Behavior maintained under second-order schedules of intravenous morphine injection in squirrel and rhesus monkeys. Under second-order schedules of morphine injection, high rates of responding by squirrel and rhesus monkeys were maintained when morphine was injected intravenously only at the end of each session. Every 30th key-pressing response during a 60-min interval produced a 2-s light; the first 30-response component completed after 60 min produced both the light and intravenous injection of morphine. A mean rate of approximately one response per second was maintained by doses of morphine ranging from 0.75-1.5 mg/kg. A pause in responding after each light presentation was followed by rapid responding until the light was produced again; pauses became shorter as the 60-min interval progressed. When brief light presentations were omitted, but morphine was still injected, response rates decreased and patterns of responding were altered. When saline injections were substituted for morphine injections, but the brief light was still presented, responding decreased markedly within three to five sessions and patterns of responding were altered.


Effects of clonidine on habituation and sensitization of acoustic startle in normal, decerebrate and locus coeruleus lesioned rats. Rats were presented with startle-eliciting tones after injection of clonidine (0.01, 0.02, 0.04, 0.08, 0.5, 1.0 or 2.0 mg/kg) or saline. Clonidine potently depressed startle amplitude and the effect was monotonically related todose. Pretreatment with piperoxane (10 mg/kg) antagonized this effect but pretreatment with phentolamine (10 mg/kg) did not. Clonidine still depressed startle in acutely decerebrate rats and in rats with bilateral ablation of the locus coeruleus. Clonidine did not interfere with sensitization to background noise and did not interfere with the ability to startle but instead improved within-session habituation. The results represent one of the few instances in the literature where a drug appears to improve habituation without directly interfering with the ability to respond. The possibility that clonidine might affect startle by stimulating central epinephrine rather than norepinephrine receptors is discussed.


Effects of pre- and post-trial caffeine administrations on simultaneous visual discrimination in three inbred strains of mice. BALB/cJ, DBA/2J, and C57BL/6J mice were injected with caffeine and tested, in the five choice Yerkes-Thompson Bryant-Bovt Nitti apparatus for patterns discrimination, in two sets of experiments. In the first the patterns were opposite oriented oblique bars, in the second U-shaped figures, one opened toward the right, the other toward the left. As concerns the saline injected animals in both sets of experiments, the BALB mice showed the highest learning abilities; in the second set the C57 strain, whose performance had not been different from that of the DBA mice in the first set, performed at the lowest level. Pre- and post-trial caffeine (5 mg/kg) administrations were followed by performance impairment in the BALB strain, while performance improvements were evident in the drugged animals belonging to the other two strains.


Relationship between tardive dyskinesia, L-Dopa-induced hyperkinesia and parkinsonism. In a study of 16 psychotic patients with neuroleptic-induced tardive dyskinesia and 16 patients with Parkinson's disease and L-Dopa-induced hyperkinesia it was found that (1) tardive dyskinesia, compared to L-Dopa hyperkinesia, was localized almost exclusively to the oral region (P mean value of 0.01), whereas theL-Dopa hyperkinesia was more pronounced in the neck (P mean value of 0.05) and the extremities (P mean value of 0.05); (2) L-Dopa hyperkinesia showed an increasing tendency to oral preponderance with age, irrespective of the severity ofParkinsonism and extra-oral hyperkinesia, while tardive dyskinesia only itensified with age, without any change in distribution; and (3) extra-oral L-Dopa hyperkinesia was related to the localization and severity of pretreatment Parkinsonism, and more to bradykinesia than to rigidity and tremor. It is concluded that the irreversible neurotoxic effect of neuroleptic drugs may be associated with age-related changes in the oral somatotopic region of the basal ganglia (to be given consideration in any future search for the pathogenetic process underlying irreversible tardive dyskinesia), and that the pathophysiology of involuntary hyperkinesia in neuroleptic-treated psychiatric patients and in L-Dopatreated parkinson patients may consist of a primary dopamine deficiency (pharmacological or structural), and a secondary relative hyperactivity in the dopaminergic system ("dopaminergic hypersensitivity") possibly corresponding to hypoactivity in the cholinergic system.


Parametric investigations of the effects of prior exposure to amphetamine and morphine on conditioned gustatory aversion. Pretreatment by a psychoactive drug can greatly attenuate the conditioning of gustatory avoidance by that drug. Although such findings have been interpreted in terms of tolerance, alternative explanations are possible. In a series of experiments, it was found that pretreatments with morphine or amphetamine massed at 24-h intervals were no more effective in attenuating conditioning than pretreatments spaced at 120-h intervals, but pretreatment with morphine provided more persistent protection against subsequent conditioning by itself than did amphetamine in a comparable previous experiment. The similarity of massed and spaced pretreatment effects can be interpreted without appealing to tolerance as a factor, but the greater persistence of morphine pretreatment implicates tolerance as a mechanism.


[Effects of methamphetamine and enriched experience on behavioral recovery after brain damage (author's transl)]. Two factorial experiments (brain status x environment x drug) were designed to measure the effects of methamphetamine and enriched experience on recovery after bilateral cortical lesions. Fisher male rats were operated or sham operated when 30 days old and thereafter raised in either an enriched (EC) or impoverished (IC) condition while daily injected with either methampheteamine (2 mg/kg) or saline. In EC, 12 rats lived together in a large cage with stimulus objects that were changed daily. In IC, a rat was kept alone in a small cage. The animals' performance was measured on a standard series of problems in a Hebb-Williams maze. The animals' scores were impaired by removal of tissue from the occipital cortex. Enriched experience, on the contrary, helped significantly in overcoming, at least partially, the effects of brain damage on problem-solving behavior regardless of whether this experience was given, for 2 h per day over a 60-day period (Expt. 1), or for 2 h per day over only a 30-day period (EXPT. 2). No drug effect was found in any of these experiments.


Enduring effects of morphine pellets revealed by conditioned taste aversion. Morphine pellets (75 mg) were implanted subcutaneously in albino rats. Three days later, following 24 h without water, these rats (Group MSN) were given access to a saccharin solution for 30 min, then injected with naloxone hydrochloride. The classical abstinence signs, including "wet dog shakes"and weight loss, were noted in these subjects, but not in controls given placebo pellets and /or saline injections. In addition, when given an opportunity to drink either saccharine solution or water 24 h later, Group MSN rats drank significantly less saccharin than any of the control groups. Similar drinking patterns were found even when naloxone injection was delayed as long as 3 weeks after pellet implantation, when none of the classical abstinence signs were seen and serum levels of morphine and its metabolites were 100 times lower according to radioimmunoassay. This simple and objective technique is thus more sensitive as a measure of prior morphine exposure than any of the commonly used indices. The continued utility of a dependent-nondependent dichotomy is also examined in light of these and other findings.


The effects of d-amphetamine on the automaintained key pecking of pigeons. Three food-deprived pigeons were initially exposed to an automaintenance procedure in which 8-s response key illuminations were followed by food delivery without regard to the subject's behavior. The percentage of occasions on which key illumination was followed by food delivery was then successively reduced from 100 to 50, 25, 10, and 2.5%. Despite the lack of a programmed contingency between key pecking and food delivery or key illumination, key pecking occurred under all automaintenance conditions. Mean responses per 8-s key illumination during non-drug sessions varied from over 15 to less than one, with the 100 and 50% pairing conditions engendering the highest rates and the 2.5% pairing condition the lowest. Under all automaintenance conditions, d-amphetamine in does of 0.5, 1, and 2 mg/kg decreased responding in a dose-dependent fashion. Rate-dependent effects were not evident despite the appreciable differences in mean response rates engendered by the various conditions.


Effects of delaying food availability contingent on ethanol-maintained lever pressing. The effects of delaying food availability 8 s contingent on every, every second, and every fourth lever press maintained by 4,8, and 16% (v/v) ethanol solutions were examined when food was initially available to rats on a fixed-interval 26-s schedule. The delay contingency decreased ethanol-maintained responding at all ethanol concentrations, with the degree of decrease inversely related to the intermittency of the delay schedule and to the ethanol concentration. Such decreases were not evident in the performance of yoked-control animals which received food coincidentally with experimental animals. Temporal changes in food presentation alone therefore could not account for the decreases produced by the delay contingency.


Antagonism of ethanol's central stimulation in mice by small doses of catecholamine-receptor agonists. Small doses of apomorphine (0.03-0.25 mg/kg i.p.) caused a dose-dependent suppression of the ethanol-induced (2.36 g/kg, 15% v/v, i.p.) locomotor stimulation in mice and higher doses (0.5--2 mg/kg i.p.) caused a delayed suppression. The delay increased with increased doses. Very small doses of clonidine (0.025 or 0.05 mg/kg i.p.), which per se did not or only slightly affect the activity of control mice, also markedly suppressed the ethanol-induced motor stimulation. Ethanol alone (2.36 g/kg i.p.) did not significantly affect the amount of Dopa accumulating in various mouse brain regions (limbic system, corpus striatum, hemispheres and brain stem) during 30 min following administration of 3-hydroxybenzylhydrazine (NSD 1015), an inhibitor of aromatic amino-acid decarboxylase. Both the hypothermia and the locomotor stimulation by ethanol were antagonized by NSD 1015. The reduction in Dopa accumulation induced by a small dose of apomorphine (0.25 mg/kg i.p.) in the dopamine-rich regions in the mouse brain was slightly enhanced by ethanol, whereas the clonidine-induced decrease in Dopa accumulation was, if anything, reduced. In conclusion, ethanol's behavioural stimulant action in mice can be largely suppressed by apomorphine or clonidine, drugs which in the small doses used probably inhibit central catecholamine (CA) neurons.


The interaction of some kynurenine pathway metabolites with 5-hydroxytryptophan and 5-hydroxytryptamine. The kynurenine pathway metabolites kynurenine, 3-hydroxykynurenine and xanthurenic acid have been tested against 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP)-induced head twitches in the mouse in a dose-range of 0.5--5.0 mg/kg. Kynurenine and 3-hydroxykynurenine were highly active. Low doses caused marked potentiation of the twitch response to both 5-HT and 5-HTP with increased toxicity of 5-HT. High doses caused antagonism of both responses. Xanthurenic acid was inactive over the same dose range. The effects of kynurenine could not be duplicated in the guinea-pig ileum. The relevance of these results to the involvement of kynurenine pathway metabolites in depressive illness is discussed.


Marijuana: effects on storage and retrieval of prose material. In a two phase design, an attempt was made to differentiate the effect of marijuana on the storage and retrieval of prose material. In the first phase, 40 male subjects were administered a single 500 mg marijuana cigarette containing 2.1%delta9-THC or a placebo cigarette. Fifteen minutes after smoking, they listened to and at the same time read a narrative passage of approximately 200 words in length. Subsequently, an immediate free recall test was given in which subjects were required to write down as much of the story as they could remember. The second phase was conducted 24h later. Marijuana and placebo subjects were randomly subdivided into four groups with half of the subjects participating in the same drug condition as occurred on day one while the others switched drug state. Fifteen minutes after smoking, all subjects recalled the passage presented on day one and then were given 24 questions concerning facts and events in the story which could be answered in a few words. These questions served as retrieval cues. Following this, a new passage was presented in the same manner as occurred on day one. After an immediate free recall test, another cued recall test was administered. Results indicated that marijuana reduced immediate recall under both cued and uncued conditions incomparison to placebo. No relative cued recall advantage was found in the marijuana groups for the old or new story and marijuana produced only a moderate decrement in recall of the old story on day two. However, marijuana given in the second phase significantly reduced memory for items recalled in the initial phase irrespective of drug or cueing condition in phase one, suggesting that retrieval was also affected. Some decrement in recall of the new story did occur as a function of drug state change in group M-P. This effect was related to the serial position of input items. Serial position did not interact with drug state under any other recall condition.


[Effects of diazepam on exploratory behavior of pigs (author's transl)]. The exploratory behavior of pigs was studied in two successive daily 20-mn sessions in a two-compartment box by counting the number of crossings from one compartment to the other and observing the activity patterns. Injection of 1 mg/kg diazepam before the first session increased the number of crossings without affecting the temporal decline of activity within the session; treated pigs did not attempt to escape the experimental situation and tended to be more perseverative in their activity patterns than control pigs. Injected before the second session, diazepam did not modify the exploratory behavior. There was no evidence of a state-dissociation effect in experimental groups for which the treatment condition differed from one session to the other. These results are discussed with respect to current theories about the behavioral effects of benzodiazepines.


Studies on human memory: the interactions of diazepam, scopolamine, and physostigmine. Seventy volunteers were injected with diazepam (0.3 mg/kg), scopolamine (8 mug/kg), or placebo, followed 70 min later by another injection of physostigmine, physostigmine and methscopolamine (in case of diazepam treatment), or placebo. Physostigmine was given in two doses, 16 and 32 mug/kg; methscopolamine, 8 and 16 mug/kg. Subjects (Ss) were tested in groups of 5 in a double blind procedure with treatments distributed according to a Latin square design. Prior to treatment, Ss heard a series of lists of words, followed by an immediate recall test. Following the first injection, delayed free recall and recognition tests were given. The second drug was then injected, followed by a presentation of another two sets of lists which were tested similarly. Subjective feelings were also evaluated with a rating questionnaire. Diazepam and scopolamine did not affect recall of information which had been learned prior to drug injection. However, both drugs impaired the learning or acquisition of new information. Physostigmine, especially in its high dose, antagonized most of the memory deficits produced by scopolamine while those of diazepam remained. This is a strong indication that scopolamine acts centrally through an anticholinergic mechanism while diazepam may act through a different system.


Open-field behaviour in sheep following treatment with the neuroleptics azaperone and acetylpromazine. The behavior of individual Romney ewes in an open field was observed after intramuscular injection of isotonic saline or two doses of azaperone (0.5, 1.0 mg/kg) or acetylpromazine (0.1, 0.25 mg/kg). Azaperone significantly reduced the distance travelled, urination, and the time spent walking. However it increased nosing of the walls and floor (investigation). Azaperone also increased the numbers of sheep seen grazing and pawing and decreased the number heart vocalizing at least once. The only effect acetylpromazine had was to reduce the number of sheep heart vocalizing. The main results were interpreted as supporting a superior reduction of emotional behaviour by azaperone. It was therefore suggested that, as with pigs, azaperone might be useful for treating stress in sheep.


Mass fragmentographic analysis of clomipramine and its mono-demethylated metabolite in human plasma. A mass fragmentographic method for the quantification of clomipramine (CIM) and monodemethyl-clomipramine (DCIM) in human plasma was developed. The deuterium labelled analogues of the compounds were used as internal standards. The sensitivity of the method allows the determination of CIM and DCIM in plasma after oral doses with a standard deviation less than 7% at concentrations of 25 ng/ml. The method was applied to the analysis of drug concentrations in plasma of clomipramine treated healthy volunteers and depressed patients. After acute treatment the level of DCIM in plasma was low as compared to chronical treatment.


Long term reduction of male agonistic behavior in mice following early exposure to ethanol. A system was developed to study the ability of early (pre- and neonatal) ethanol input to induce long lasting neural and behavioral changes. Ethanol was administered to E7b1/10bg and DBA/1Bg offspring through their parents who received 10% ethanol as their only liquid supply either before and during pregnancy, or from delivery until 14 days post partum, or during both periods. Thus, the offspring received ethanol transplacentally and/or through the mother's milk. The present paper is concerned with the male agonistic behavior at age 50 days of the treated offspring as compared with their pair fed controls. Early ethanol input resulted in a 23% increase in latency to attack in C57 mice and 58% in DBA, as well as a 49% (C57) and 38% (DBA) decrease in time spent fighting. The sensitive period to ethanol effect was apparently postnatal. Prenatal administration had no effect on agonistic behavior. DBA offspring were more aggressive than C57 and the scores of C57 offspring were more variable, thus indicating a lower phenotypic buffering in this strain.


Evidence for a probenecid-sensitive transport system of acid monoamine metabolites from the spinal subarachnoid space. The location of probenecid-sensitive elimination mechanisms of monoamine metabolites from the cerebrospinal fluid of the cat was determined with ventriculo-cisternal or ventriculo-lumbar perfusion techniques. These techniques were described in detail. Levels of endogenous homovanillic acid and 5-hydroxyindoleacetic acid were assayed in the perfusate. Probenecid administration induced the most marked increase of the levels of the monoamine metabolites in the ventriculo-lumbar perfusates. It was concluded that probenecid blocked the transport of both metabolites from the spinal subarachnoid space.


Circadian rhythms of ethanol consumption by mice: a simple computer analysis for chronopharmacology. On the assumption that a sinusoidal curve adequately described the circadian rhythm of food or fluid consumption by mice, the whole daily pattern can be derived from a few observations. Examples are presented to show that the assumption is valid. This simple curve-fitting by computer is also applicable to analysis of blood levels of drugs administered in the food or drinking fluid. The method should be useful for estimating the magnitude of daily fluctuations in pharmacological variables, including drug intake rates and circulating drug levels.


Propranolol effects on acute marihuana intoxication in man. To investigate the possible interaction of a beta adrenergic blocking agent and marihuana, six healthy experienced marihuana smokers received the two drugs separately and in combination. Propranolol (120 mg per os) reduced resting HR and BP; there were no changes in performance on tasks designed to test psychomotor speed, attention, memory and learning. Marihuana (10 mg delta9-THC), administered in smoke, induced the typical subjective state ("high") with marked increases in HR, BP and conjunctival injection; it impaired performance on a learning test without significantly affecting attention. Pre-treatment with propranolol blocked effectively the cardiovascular effects of marihuana; it prevented the learning impairment and, to a lesser degree, the characteristic subjective experience.


Rapid induction and quantitation of morphine dependence in the rat by pellet implantation. Four schedules of subcutaneous morphine pellet implantation were developed to render rats rapidly physically dependent on morphine. The schedules included implantation of four morphine pellets over a 3-day period (schedule 1), six morphine pellets over a 3-day period (schedule 2), six pellets over a 7-day period (schedule 3), and ten pellets over a 10-day period (schedule 4). Each morphine pellet contained 75 mg of morphine base. The degree of morphine dependence was quantitated by determining the median effective dose (ED50) of naloxone required to induce the stereotyped jumping response. Hypothermia and weight loss, during abrupt and naloxone-induced withdrawal, were also measured. Rats on schedule 4 exhibited a high degree of dependence on morphine as evidenced by an extremely low naloxone ED50 for the precipitated withdrawal jumping response, whereas schedules 1 and 2 produced a low degree of dependence as shown by high naloxone ED50's. Further evidence for a high degree of physical dependence on morphine is schedule 4 rats was indicated by their greater loss in body weight and greater hypothermic response after abrupt and after naloxone precipitated withdrawal compared with these responsed in the rats in the other three schedules. A correlation was found to exist between naloxone ED50 for the jumping response, body weight loss, and hypothermia observed during naloxone-induced withdrawal in morphine-dependent rats. These studies suggest that the implantation of four morphine pellets in the rat produces a mild degree of dependence and that caution should be exercised when making generalized conclusions about the biochemical correlations involved when four or less number of pellets, each containing 75 mg of morphine base, are used to induce morphine dependence in the rat.


The reinforcing action of morphine and its paradoxical side effect. Rats were trained to run down a runway for food in the goal box, and were then tested with one trial per day for 5 days. After running in the runway and eating in the goal box each rat was injected with a drug and returned to the empty goal box for 50 min. Over the 5 trials, rats that received morphine sulphate increased their running speed approximately 400% while the amount of food they ate in the goal box decreased to about 70% of baseline values. The running speed of rats that received lithium chloride decreased to about 30%, while the amount of food they ate decreased to less than 10% of baseline. These two variables did not change for rats that received saline injections. The large increases in running speed observed in the rats that received morphine injections were attributed to an interaction (but not simple summation) between the positive reinforcing effects of morphine and food. The accompanying paradoxical decrease in amount eaten was discussed in terms of the complex pharmacological properties of morphine and it was suggested that morphine may have a reinforcing effect on behavior that is independent of its affective properties.


Facilitation by dexamethasone of tolerance to ethanol in the rat. The purpose of this study was to examine the relationship between the development of tolerance to ethanol and the hypothalamic-pituitary-adrenal cortex (H-P-AC) system by modifying the H-P-AC system through the use of a synthetic glucocorticoid, dexamethasone. Also this study determined whether repeated drug administration and environmental adaptation would facilitate development of tolerance. Rats injected daily with dexamethasone and ethanol showed an antagonism to the acute effects of ethanol and a higher rate of tolerance development to the depressant effect of ethanol than animals administered ethanol only. These results were discussed in relation to a possible stimulant effect of dexamethasone on behavior, an increase in the metabolism of ethanol, and a possible accumulation of dexamethasone in the brain, affecting an organism's response to ethanol. It also was shown that daily ethanol administration and adaptation to the testing environment facilitated the development of tolerance, compared to ethanol administration only.


Effect of muscarinic cholinergic drugs on morphine-induced catalepsy, antinociception and changes in brain dopamine metabolism. The effects of drugs acting on muscarinic cholinergic receptors on the catalepsy, antinociception and changes in rectal temperature and in brain dopamine metabolism induced by morphine were studied in Wistar rats. Scopolamine (0.3 - 30 mg/kg) was about three times as potent as atropine (1 - 30 mg/kg) in potentiating the cataleptic effect of morphine. Methylscopolamine and methylatropine did not alter the cataleptic effect of morphine. Pilocarpine (100 mg/kg) and arecoline (10 mg/kg) slightly but significantly and RS86 (20 - 40 mg/kg) clearly antagonized the morphine-catalepsy. RS86 antagonized the atropine-induced potentiation of morphine catalepsy. The antinociceptive effect of pilocarpine was additive and that of RS86 less than additive with morphine. The antimuscarinic compounds did not alter the antinociceptive effect of morphine. Antimuscarinic compounds enhanced the hypothermic effect of morphine, but none of the compounds studied altered the hyperthermic effect of morphine. The antimuscarinic drugs reduced the concentration of striatal homovanillic acid (HVA) in about same proportion in control and morphine-treated rats. Both the muscarinic compounds and morphine increased the concentration of striatal HVA, but when combined their effects were not significantly different from those of morphine alone. Scopolamine antagonized and pilocarpine accelerated the morphine-induced increase in the rate of depletion of cerebral dopamine content. The present results show that the effects of muscarinic aand antimuscarinic cholinergic drugs on the cataleptic effect of morphine were opposite to their effects on the catalepsy induced by neuroleptic compounds.


Clinical pharmacological studies of tandamine, a potential antidepressive drug. Tandamine hydrochloride, a thiopyranoindole, was more active than desmethylimipramine in inhibiting the tyramine pressor response after single oral doses in human volunteers. When compared with a placebo, tandamine was found to possess significant anticholinergic activity, to reduce appetite and to produce sedation. Compared with clomipramine, it caused a smaller inhibition of 5-HT but a more marked inhibition of dopamine uptake into human platelets. Further clinical and pharmacological studies with tandamine may help to elucidate the respective roles of different monoamines in depression, sedation and appetite.


Effect of tryptamine antagonists on self-stimulation. Interaction with amphetamine. In order to investigate the role played by serotonergic mechanisms in self-stimulation (SS) behavior, the effects of two tryptamine antagonists, cyproheptadine and methysergide on SS were measured. Also the influence of antitryptaminic drug pre-treatment on the facilitatory effect of amphetamine, a pro-adrenergic drug, on SS was studied. Rats with brain electrodes permanently implanted at the lateral hypothalamus and trained to lever-press for response-contingent brain electric stimulus presentation were used. Stimulus current was maintained at threshold level. Both tryptamine antagonists used potentiated the enhancing effect of amphetamine on low SS rates, displacing to the left its dose-effect curve; cyproheptadine was at least three times more potent than methysergide. In addition, cyproheptadine, but not methysergide, caused dose-related increases in SS rate, when given alone. These results suggest that brain serotonergic systems play an inhibitory role in SS, opposing the facilitatory influence of adrenergic mechanisms.


Dissociation of the anti-punishment activities of chlordiazepoxide and atropine using two heterogeneous passive avoidance tasks. The effects of chlordiazepoxide and atropine on the acquisition of passive avoidance learning in rats were compared in two superficially similar but theoretically distinct forms of the step down task in an attempt to dissociate behaviourally the disinhibiting effects of these two classes of drug. In a discrete trial procedure both chlordiazepoxide and atropine significantly retarded acquisition; on retention testing under saline treatment alone, the initial chlordiazepoxide group showed no change in behaviour while the initial atropine group showed a facilitation. In a continuous trial procedure, however, atropine but not chlordiazepoxide produced an increase in the total number of step downs; despite this, these groups showed acquisition at similar rates, though learning was not shown on retention testing under saline alone. These results enabled the two classes of drug to be distinguished. The nature of the heterogeneity between the two test paradigms is discussed, and results interpreted in terms of possible differential drug effects on punishment and escape components of the tasks.


Pargyline-induced increases in sensitivity to the effects of drugs on operant behavior in pigeons. Pigeons responded under a multiple fixed-interval 5-min, 30-response fixed-ratio schedule of food reinforcement. Acute pargyline doses between 10.0 and 50.0 mg/kg (i.m.); given immediately prior to the session, decreased responding. Daily administration of 50 mg/kg pargyline (24 mg/kg, every 12 hr) initially decreased responding. Tolerance developed so that after 4 days of daily pargyline, responding had returned to control values. Chronic pargyline resulted in an enhanced sensitivity to the effects of d-amphetamine, ephedrine, tyramine, and morphine on schedule-controlled responding. Both d-amphetamine and pentobarbital increased fixed-interval responding at relatively low doses, while higher doses decreased responding. Daily pargyline resulted in an increased sensitivity to both the increases and decreases in response rates produced by d-amphetamine. In contrast, sensitivity to pentobarbital was not changed after daily pargyline, Ephedrine, tyramine, and morphine only decreased fixed-interval responding. Chronic pargyline resulted in an increased sensitivity to the response-rate decreasing effects of ephedrine, tyramine, and morphine. In addition to the increased sensitivity of fixed-interval responding to the effects of tyramine, the dose-effect curve for fixed-ratio responding was also a shifted to the left. Daily pargyline did not result in changes in sensitivity of fixed-ratio responding to the effects of the other drugs tested.


[Multiple vascular stenoses in neurofibromatosis (author's transl)]. Vascular lesions due to neurofibromatosis have been predominantly reported in the renal arteries as cause of arterial hypertension, but they can occur everywhere. The angiography shows a smoothly bordered stenosis at the origin of the artery with an elongated funnel shaped poststenotic deformity. Collateral vessels are often present. Reconstructive arterial surgery is in a high percentage successful. The main differential diagnosis includes fibromuscular dysplasia. Arterial hypertension in a young person with neurofibromatosis should suggest the presence of pheochromocytoma or renovascular disease.


An improved 191Os-191mIr generator for radionuclide angiocardiography. 191mIr is a useful tracer for radionuclide angiocardiography and may be of particular value in the evaluation of heart disease in children. It has a short half-life, a suitable photon energy, and may be obtained as a generator product by decay of its long-lived parent 191Os. A 191Os-191mIr generator capable of providing at least 18 mCi of 191mIr in 1.5 ml of eluant is described. 191mIr is separated from 191Os by absorbing 191OsCl6(-2) on an ion exchange resin and eluting with a solution of 8.7% NaCl at a pH of 2.2. The generator employs an additional resin column which is replaced to minimize 191Os breakthrough.


Cure of EMT-6 tumors by X rays or neutrons: effect of mixed-fractionation schemes. EMT-6 mouse tumors were treated with (a) 1 or 5 fractions of either x rays or neutrons or (b) a mixture of both in which 2 fractions of neutrons (n) plus 3 fraction of x rays (x) were given in 5 days in the sequence n-n-x-x-x or n-x-x-x-n. Using local tumor control as an end point, neutron RBEs of 1.7 for single fractions and 2.6 for 5 fractions were obtained. The two mixed schemes yielded RBEs of 1.5 and 1.4, respectively. Therapeutic gain factors, calculated as the ratio of tumor to skin RBE with neutrons or mixed radiations, were highest for the mixed fractionation schemes. These results are due to an apparent enhancement of the neutron effect in the tumor but not in the skin with these regimens. Other normal tissues must be irradiated with mixed schemes to determine whether this phenomenon is limited to the skin.


Quantitative assessment of para-osteo-arthropathy and its maturation on serial radionuclide bone images. Paraplegics whose range of motion is limited by para-osteo-arthropathy (POA) may have difficulty in becoming independent unless the heterotopic bone mass is removed. The recurrence rate is high if the bony mass is not mature at the time of surgery. Radiography and alkaline phosphatase correlations are not trustworthy. In 3 paraplegics with POA, radiolabeled osteotropic agents demonstrated a steady decrease in the uptake ratio (heterotopic/normal bone) followed by a steady-state plateau, reflecting the most useful index of maturation and allowing surgical removal of bone without recurrence.


A computer-assisted method to determine the diagnostic efficacy of computed tomography of the body. A computer-assisted system has been devised to provide objective measurements of the diagnostic efficacy of CT of the body. The diagnostic efficacy of CT is compared with that of UGI examinations for 574 patients. The potential usefulness of this system in cost effectiveness studies, diagnostic efficacy studies, and clinical efficacy studies is examined.


Obervations on subjective symptomatology, coping behavior, and medical decisions is asthma. The Asthma Symptom Checklist (ASC), describing the subjective symptoms reported to occur during asthmatic attacks, has been developed previously. In the present study, the ASC key cluster solution was replicated and refined within a sample of 374 asthmatic inpatients. All of the original symptom categories were reporduced, including two mood categories, Panic-Fear and Irritability, a Fatigue category, and two somatic categories. Hyperventilation-Hypocapnia and Airway Obstruction. Two refinements were notable: (1) The Airway Obstruction category was empirically divided into two conceptually clear components, Dyspnea anc Congestion, and (2) three secondary mood categories, Worry, Loneliness, and Anger, were identified, which describe a continuum of mood between the polar extremes of panic and irritability. Of the symptom categories, only Panic-Fear was related to the intensity of the discharge drug regimens recommended 2 to 6 mouths after ASC administration. Panic-Fear scores were independent of pulmonary function measurements. A combined index based on pulmonary functions and panic-fear yielded the best prediction of discharge steroid regiments. Finally, those physicians rated highest in "sensitivity" to their patients by their supervisors prescribed less steroids overall, but most frequently prescribed discharge steriod regimens in relation to their patients' Panic-Fear scores. In contrast, physicians rated lower on sensitivity prescribed higher steroid regimens overall, but based these drug recommendations more cleary on objective pulmonary functioning, and not in relation to their patients' Panic-Fear scores. The results strongly suggest that the ASC Panic-Fear scale is associated with coping behaviors that importantly affect the patient's overall clinical picture by increasing the apparent severity of the asthma, thereby leading to intensified treatment. The findings stress the need to evaluate independently the objective medical condition and subjective symptomatology with its related coping behavior, in order to direct appropriate modes of therapy to each.


Elevated prostaglandins synthetase activity in methylcholanthrene-transformed mouse BALB/3T3. Cell lines transformed from 3T3 spontaneously, by radiation, or by treatment with chemical carcinogens, polyoma and SV40 virus produce up to 5 times more prostaglandins than their untransformed parent line. Several aspects of prostaglandin biosynthesis by MC5-5 and 3T3 were compared. When stimulated by serum, bradykinin, or thrombin, MC5-5 cells labeled with radioactive arachidonic acid in their cellular lipids, these higher levels were shown not to be due to increased availability of the prostaglandin precursor, arachidonic acid. Prostaglandin synthetase activity in microsomal fractions prepared from MC5-5 was 6 times higher than that of microsomes of untransformed cells. The increased prostaglandin levels produced by transformed cells therefore appear to be the result of elevated prostaglandin synthetase activity.


On the mode of action and biochemical properties of anti-inflammatory drugs-II. The inhibition of prostaglandin (PG) synthetase by nonsteroidal anti-inflammatory drugs (NSAID) is not well understood. Co-factors (glutathione and hydroquinone) are needed for maximum enzymatic activity in vitro, and we suggest that NSAID might inhibit PG synthetase partly by interfering with co-factor induced stimulation of the enzyme. This hypothesis was tested by: A) Examining the effect of glutathione, noradrenaline and hydroquinone on bull seminal vesicle (BSV) PG synthetase in vitro. The stimulatory effects were concentration-dependent. B) Three structurally distinct NSAID, indomethacin, aspirin and paracetamol, inhibited the stimulation by each co-factor in a concentration-related manner. Drug effectiveness also depended on the concentration of co-factor.


Effects of bilirubin on glucuronidation of p-nitrophenol and morphine. Addition of bilirubin in vitro to hepatic microsomes or 9,333 g supernatant activated UDP glucuronyltransferase activity (UDPGT) for p-nitrophenol of livers from Sprague-Dawley rats, Wistar rats, icteric Gunn rats and nonicteric Gunn rats. However, injection of bilirubin at subtoxic doses using a variety of regimens failed to produce detectable activation of UDPGT in intact or bile duct-ligated rats. Pretreatment with intraperitoneal injections of bilirubin increased the rate of morphine glucuronide excretion in both Sprague-Dawley and icteric Gunn rats. Sulfadimethoxine did not affect morphin e excretion in Gunn rats. The data suggest that activation of UDPGT is of little, if any, significance in hyperbilirubinemia although the basis for increased excretion of morphine following bilirubin pretreatment has not been established.


A theoretical analysis of the distribution of thyroxine among sites on thyroid binding globulin, thyroid binding prealbumin, and serum albumin. A mathematical analysis was made of the distribution of free and bound thyroxine among the following: one site on thyroid binding globulin, and two sets of sites on thyroid binding prealbumin and human serum albumin. Computations were carried out using reported association constants and binding capacities as input values for a recently developed computer program. Most of the thyroxine was bound by thyroid binding globulin and the high affinity sites on thyroid binding prealbumin and human serum albumin. Computations were carried out for normal and abnormal levels of thyroxine and the binding proteins.


[Transverse axial computerised tomography of the brain in partial epilepsy]. Two hundred epileptics presenting with partial epileptic attacks were subjected to investigation by Acta-Scanner. Results were normal in 100 cases. Also found were 20 tumours (13 of them astrocytomas), 7 epileptogenic softenings, 41 cerebral atrophies, 8 of which were porencephalies, 5 calcifications (3 isolated, 2 multiple, connected with Bourneville's disease), 5 post-operative lesions and 22 dubious conditions. Various correlations between the results of scanning, the clinical findings and the E.E.G. are considered. The value of scanning in screening for tumours developing under the cloak of isolated epilepsy is emphasized and attention is drawn to certain difficulties of interpretation.


[Partial epilepsy with complex symptoms and atrophic occipito-parietal lesions. Value of tachoencephalographic examination]. Eleven of the first 500 epileptics examined by axial tomography presented pseudo-porencephalic dilation (cavitary atrophy) of an occipital horn, associated or not with more extensive ventricular dilation. This lesion was found in 2.2% of all the epileptics and in 5% of the epileptics under the age of 20 in this group, a high incidence when compared with that of lesions of the same type located elsewhere. Clinical investigation and E.E.G. carried out on these 11 children showed that they were suffering from either hemiphegia or hemiparesis (8 out of 11 cases) and hemianopsia (7 out of 11 cases), and had serious epilepsy with partial fits (6 cases), usual temporal lobe epilepsy (5 cases), generalized secondary epilepsy (3 cases) or epilepsy defying classification (2 cases). These cases are compared with those recently published by Remillard, Ethier and Anderman. These authors consider that these cerebral lesions are the result of peri-natal thrombosis of the posterior cerebral artery. But in our group of cases, angiographic results do not appear to justify this claim.


Effect of drying on viability of periodontal membrane. The influence of a dry extra-alveolar period on the viability of cells in the periodontal membrane of human and monkey teeth was examined in vitro. Extracted mature teeth were allowed to dry for 0, 30, 60, 90, and 120 min. Cell viability was examined with the following methods: 1) Culturing the teeth with subsequent typsination and counting of viable cells. 2) Culturing the teeth with subsequent vital staining of the root surface with neutral red and estimation of the vital stained periodontal membrane area in percentage of the total root surface. Both methods revealed that the number of viable cells in the period declines very rapidly with an increase in drying time. After 2 h it was not possible to demonstrate cell viability using tissue cultrue technique.