Antibodies of surface antigens of lymphocytes and lymphoblastoid cells in cold-agglutinin-positive sera from patients with Mycoplasma pneumoniae infection. IgM antibodies reacting in the cold with surface antigens of normal human blood lymphocytes were demonstrated by indirect immunofluorescence (IFL) in cold-agglutinin-positive sera from 21 patients with Mycoplasma pneumoniae (MP) infection. Twenty to fifty per cent of the lymphocytes were stained. MP sera reacted also with 75%-100% of cells from two lymphoblastoid cell lines and one Burkitt lymphoma line and with about 80% of peripheral blood lymphocytes from one patient with chronic lymphatic leukaemia. The IFL reaction was negative with cells from leukaemic lymphoid T-cell line (Molt-4). Lymphocyte fractionation experiments gave no evidence of a selective reactivity of MP sera and B or T lymphocytes of peripheral blood. Removal of cold agglutinins from the MP sera by absorption with human O erythrocytes significantly reduced the IFL reactivity with lymphocytes and lymphoblastoid cells, indicating the presence of I antigen on these cells. Furthermore, lymphoblastoid cells but not Molt lymphoid cells absorbed out most of the cold erythroagglutinins.


Multiple lymphonodular cryptococcosis, cured by 5-fluorocytosine. A 5-year-old boy was admitted with an acute febrile illness and painful and enlarged cervical lymph nodes. A chest X-ray showed right tracheobronchial lymph nodes. A lymph node biopsy demonstrated a tuberculoid appearance, with epitheloid cells, giant cells, and also necrotic zones. Cryptococcus neoformans was isolated both in culture and after animal inoculation. While amphotericin B was not tolerated by the patient, the oral administration of 5-fluorocytosine resulted in a rapid recovery.


Morphogenesis and pathogenesis of chronic lung diseases. VIII. Cellularization of lung interlobular areas as a preliminary phase of peribronchovascular fibrosis. An experimental investigation of the lung interlobular areas was performed by elicitation of rabbits with antigens (aspergillar and human-serum proteins) administered in aerosols or intramuscularly in Freund's adjuvant. The cell accumulations in the interlobular areas developed irrespective of the antigen, duration of exposure and route of administration. The cells accumulated (reticulo-lymphoid, plasma cells, eosinocytes) were counted and the areal surface measured. The total cell count and the proportion of plasma cells appeared to be related to time, dose and antigenicity of the proteins administered. Fibrillogenesis was also observed between cells in the interlobular areas during prolonged administration of antigens, pointing out the importance of the interlobular lesions in chronic lung processes.


[The application of relaxation in hospital geriatrics]. On a three years base experience in the geriatric department of Geneva's university psychiatric clinic, the paper studies among practical problems encountered in the application in institutional geriatry of relaxation, those related to therapists' training and to the nature of therapy control established for them and their patients. Problems pertaining to the management of the cure according to the method of J. de Ajuriaguerra amd M. Cahen are viewed, and the position of relaxation in the post-graduate psychiatric training defined. The study also mentions the influence of relaxation applied to the aged patient on his human environment in and out of the hospital. These notes are complementary to those already presented on the indications of relaxation in geriatry, the way body is preceived by the aged patient through relaxation, and it's consequences on the adjustment of an aging person.


["Senile" chronic pancreatitis; a new nosologic entity? Studies in 38 cases. Indications of a vascular origin and relationship to the primarily painless chronic pancreatitis]. 47 of 170 cases of chronic pancreatitis observed and controlled in the last 12 years in this department were of unknown etiology (idiopathic form). The age distribution of these 47 cases showed 2 peaks, a "juvenile" group of 9 cases (average age 29 years) and a "senile" group of 38 cases (average age 62  years). Idiopathic "senile" chronic pancreatitis (ISCP) is characterized by advanced age at the time of first manifestation (95% over 50 years), a prevalence of males (81%), a high incidence of calcifications (60%) and a rather benign, often painles course (74%). Clinically there is some overlap between ISCP and painless chronic pancreatitis (PSCP). In contrast to PSCP, ISCP seems, however, to comprise a homogeneous group of patients as far as etiology is concerned, and typical episodes of pancreatitis occurred in about 25% of cases with ISCP. Ther is an unusually high incidence of signs of arteriopathy associated with ISCP. Arteritis of the lower limbs and/or coronary heart disease was detected in 42% of cases, 14 of 17 deaths were due to cardiovascular disease and arteriosclerotic risk factors were found in 87% of the patients. In our experience ISCP seems to be a special form of chronic pancreatitis which can be differentiated from alcohol-induced chronic pancreatitis and from the other forms with rare causes. Furthermore, our findings suggest that a vascular factor is of importance in causing ISCP.


The prevalence of ampicillin, cephalosporin and sulphonamide resistance amongst urinary tract pathogens. A total of 2,031 clinical isolates of Gram negative bacilli was obtained from hospitals in 4 centres and these cultures were tested for resistance to ampicillin, cephazolin and sulphonamide. Ampicillin and sulphonamide resistance in outpatients ranged from 15 to 28 per cent of E. coli strains and 4 to 11 per cent of Proteus mirabilis strains. Resistance to cephazolin in outpatients ranged from 0 to 3 per cent of E. coli and 0 to 6 per cent of Proteus mirabilis. Resistance patterns for E. coli, Proteus mirabilis and Klebsiella strains isolated from inpatients were much higher and varied widely. These patterns are presented and the reasons for these variations discussed.


Beta-lactamase resistance of cephazolin and other cephalosporins. The turbidities of cultures of bacterial were monitored continuously at 37 degrees C. in a biophotometer. In the early phase of logarithmic growth, at approximately 2 X 10(7) organisms per ml., antibiotic was added. A strain of Escherichia coli (E. coli) that was ampicillim-resistant, but cephaloridine-sensitive, produced beta-lactamase rapidly as shown by the breakdown of a chromogenic cephalosporin. The E. coli was lysed by cephaloridine 15 minutes after the addition of the antibiotic, but, even with a concentration 8-fold greater than the MIC, after 3.5 hours the antibiotic was not detectable in the culture medium and the strain had recommenced logarithmic growth. In the presence of a concentration of cephazolin 4-fold greater than the MIC the E. coli lysed after 30 minutes and did not recommence growth 6 hours, indicating much slower destruction of the antibiotic, presumably due to the greater beta-lactamase resistance of cephazolin. Similar results were obtained with other E. coli and a strain of Klebsiella pneumoniae.


Cephazolin: a comparison to ampicillin in respiratory and urinary infections with dosage regulation by a nomogram. Cephazolin sodium was shown to be as effective as ampicillin in the treatment of respiratory and urinary system infections in patients who were infected with susceptible organisms and had a much less troublesome side reaction rate of hypersensitivity type. In addition, it was found that predictable blood levels of cephazolin could be obtained in patients with renal failure when dosage was regulated according to a nomogram calculated from the patient's serum half-life based on clearance of creatinine.


Low dose, long-term treatment of rheumatoid arthritis with azathioprine. Sixteen patients with classical rheumatoid arthritis which had been present for longer than two years, representing anatomic stages II-IV, were treated with azathioprine in doses of 50 to 175 mg/day. They were followed up for up to six years. Using the criterion of ability to work, 93% of the patients improved markedly during the time observed. Complement levels were low before treatment and tended to stabilize within the normal range as the disease became less active. Erythrocyte sedimentation rate (ESR) fell during therapy but changes in ESR did not correlate well with the patients' clinical states. Titers of rheumatoid agglutinins showed little change after as long as six years of therapy. When all patients were stable a double-blind cross-over study, using a placebo tablet, was instituted. Fifteen of 16 patients had a marked exacerbation of disease activity after receiving placebo for three to eight weeks. When azathioprine was reinstituted, gradual improvement again occurred so that all patients were back to their asymptomatic or mildly symptomatic state within seven months.


Interrelationships between platelets and coagulation in the pathogenesis of venous thrombosis. The relationship between platelets and coagulation in the pathogenesis of venous thrombosis is reviewed. Platelet coagulant activities, coagulation factors and platelet numbers were measured pre- and postoperatively in patients who underwent hip surgery. About 50% of patients developed venous thrombosis. No significant pre-operative differences were observed in platelet coagulant activities between the group of patients who developed thrombosis and the group who did not. However, platelet counts and coagulation activities were significantly higher postoperatively in patients with thrombosis. The postoperative increase in platelet activity preceded venographically observable thrombosis. The author concludes that in patients with thrombosis there may be an increase of young platelets which are 'hyperactive' and which may trigger thrombosis in areas of stasis. It is not impossible that the increased platelet coagulation activity was the result rather than the cause of thrombosis. However, the temporal sequence of effects observed militate against this possibility.


Prolonged rupture of fetal membranes and neonatal infections. Fifty-one babies with prolonged rupture of fetal membranes (longer than 24 hours) were studied for evidence of latent infection. Cord blood was taken from all babies for a full blood count and blood culture. Gastric aspirates were  collected and vernix swabs were taken immediately after delivery. Microscopy, culture and antibiotic sensitivity tests were done on the appropriate specimens. Each baby had a thorough medical examination immediately after birth, and 3 and 7 days afterwards. After the initial investigation they were allocated to a treatment (penicillin 50 000 U/kg/d and kanamycin 10 mg/kg/d) or a non-treatment group by randomised card selection. Six patients became infected, as was shown by a positive blood culture, while 4 of the 6 had clinical signs of infection as well. These infants were treated with penicillin and kanamycin, and all did well. None of the remaining babies showed any signs of infection. There were no deaths. Blood culture was found to correlate well with clinical infections, and many be used as a guide to latent infection and treatment.


Bone marrow reconstitution using a block grafting technique. Experiments in rabbits with radiation-induced bone marrow aplasia have demonstrated that intramedullary block grafting is a feasible procedure. This technique requires surgical interference and offers no advantage over intravenous reconstitution. We therefore suggest that it has no value in therapeutic bone marrow transplantation.


Oxprenolol and propranolol in anxiety states. A double-blind comparative study. The efficacy of oxprenolol (Trasicor) and propranolol in controlling anxiety was compared in a double-blind study of patients with anxiety and tension. Efficacy was assessed by the investigator with the aid of a psychiatric rating scale consisting of 19 items, bythe patients using visual analogue scales, and by the investigator's and the patients' over-all assessments. Tolerance to the drugs was evaluated by over-all assessment and by means of a checklist of signs and symptoms which emerged during treatment. Little difference in the efficacy of the two drugs was observed. Both were effective in the treatment of anxiety and tension. In general, oxprenolol was significantly better tolerated than propranolol. Evidence of the intrinsic sympathomimetic activity of oxprenolol emerged during the course of the study or, alternatively, evidence that propranolol had a greater cardiac-depressant effect.


[Study of various aspects of the pathogenesis of Candida albicans infections]. Nutritional competition between Candida albicans and 6 bacteria frequently found in the gastro-intestinal tract, together with the influence of the bacterial supernatant on yeast growth were studied. Our results showed that the amount of available carbohydrates in vitro was an important growth factor. Three of the 6 carbohydrates enhanced growth. The hypothesis of an antifungal substance produced by bacteria cannot be excluded though a 10% concentration of bacterial supernatant had no inhibitory effect on fungal growth and germination. In the presence of bacteria, the percentage of germ tube formation was markedly reduced in horse serum after 4 h incubation at 37 degrees C.


Cryptococcus neoformans of saprophytic origin. Cryptococcus neoformans was isolated on 276 occasions as follows: from pigeon faeces, 159 (45%) of 349 samples; pigeon crops, 39 (50%) of 80 crops; from drinking water, 37 (74%) of 50 samples; from the atmosphere, 3 strains in a contaminated loft. It was also recovered from 38 (19%) of 200 samples of canary faeces. It is possible that C. neoformans survives in the crop of pigeons and occasionally passes to the faeces where it multiplies. The factors influencing its presence are: the irregular cleaning of lofts, overcrowding and air-pollution from poor ventilation.


The relative susceptibility of New Zealand black and CBA mice to infection with opportunistic fungal pathogens. The susceptibility of ageing New Zealand Black (NZB) mice to infection with a number of opportunistic fungi and yeasts wsd compared with that of similarly aged mice of the CBA strain. The NZB mice showed a greater susceptibility to lethal infection with Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans than did those of the CBA strain. Both mouse strains showed similar susceptibility to lethal infection by Allescheria boydii, Absidia corymbifera, Mucor pusillus and Rhizopus oryzae. The clinical and histopathological characteristics of the infections produced by Allesch boydii,  Asp. fumigatus, Abs. corymbifera, M. pusillus and R. oryzae were similar for both mouse strains. In contrast C. albicans and Crypto. neoformans produced much more severe infections in NZB mice than in CBA mice. These results suggested that T-lymphocyte dependent immune processes played a major role in resistance to C. albicans and Crypto. neoformans but not to Abs. corymbifera, Allesch. boydii, Asp. fumigatus, M. pusillus or R. oryzae.


Effect of antibodies on the respiration and morphology of Candida Albicans. Respirometry was used to study the effect of antibodies to Candida albicans on the gowth of this species in vitro. Blastospore suspensions were pre-incubated with rabbit hyperimmune and normal serum and rabbit antibody and normal gamma globulin at 37 degrees C for 30 minutes. They were then inoculated into respirometer flasks containing a semi-synthetic medium and oxygen consumption was measured at 27 degrees C. Rabbit antiserum to C. albicans serotype A inhibited the growth, as measured by O2 consumption, of serotyped A and B strains of C. albicans. The amount of inhibition appeared to be related to the prevention or retardation of germ tube formation. The growth of blastospores incubated with normal rabbit serum was filamentous, whereas, blastospores incubated with antiserum remained in the yeast phase. Inhibition of O2 consumption and retardation of germ tube formation was also demonstrated with the purified gamma-globulin fraction of the antiserum.


Primary excision and prompt grafting as routine therapy for the treatment of thermal burns in children. There is much evidence that the most important factor in the successful treatment of skin destruction after thermal injury is to remove dead tissue and promptly close the wound. While the exact methods employed to achieve this goal may vary, in the cases reported here three basic methods were used: (1) simple excision of burn eschar with immediate closure with autograft for small and medium-sized burns; (2) excision and immediate wound closure with autograft supplemented by allograft, with replacement of allograft by autograft before extensive allograft rejection, for large burns; and (3) immunosuppression and temporary skin transplantation for massive third degree burns. All have markedly decreased hospital stay and complications, and in large and massive burns mortality was substantially reduced.


Surgical radiation therapy with vicryl-125I absorbable sutures. A convenient method of interstitial radiation therapy can be quickly and easily accomplished using absorbable Vicryl-125I sutures which offer these general advantages: long shelf life, 60 day half-life; low energy, 28 kilo electron volts, permitting patients to leave the hospital; good geometric and anatomic distribution of 125I seeds which remain in place after implantation; less radiation exposure to the operating and attending personnel due to this low energy plus the reduced exposure time provided by quick implantation; removal unnecessary, reducing exposure time; implantation using minor surgical equipment; dosage determination easily calculated; hospitalization, from the standpoint of radioactivity, unnecessary.


Effects of preventive antibiotics on neutrophil phagocytosis as measured by the nitroblue tetrazolium dye test. White blood cell counts and nitroblue tetrazolium dye tests were performed in three groups of dogs before and after the injection of Escherichia coli using colistimethate sodium and cephalothin sodium in the second and third groups, respectively, prior to the induction of sepsis. The response was a diminished white blood count and increased nitroblue tetrazolium dye test percentage in all groups. When antibiotic administration was performed prior to the induction of sepsis, the increase in the nitroblue tetrazolium reduction dye test was much more evident despite the overwhelming dose of bacteria given, suggesting that antibiotics given preoperatively will prevent the toxic effects of bacteria on the neutrophil and will enhance the phagocytic activity of the neutrophil.


Direct effect of endotoxin on the gastric mucosal microcirculation and electrical gradient. The effects of intra-arterial infusion of E. coli endotoxin at 1.0 mg. per minute on the gastric total and mucosal blood flows, electrical potential difference, and ionic fluxes across the gastric mucosa were studied in an exteriorized, chambered preparation of canine fundic stomach. Gamma-labelled microsphere technique was used in addition to venous drainage and plasma aminopyrine clearance for the measurement of total and mucosal blood flow, respectively. In spite of normal systemic blood pressure throughout the experiment, E. coli endotoxin infusion caused a significant decrease in total gastric blood flow and in the fractional distribution of flow to the mucosae. There was no significant arteriovenous shunting of microspheres. Significant reduction in potential difference and hydrogen-ion back diffusion also was noted after endotoxin infusion, possibly as a consequence of reduced mucosal blood flow. The results indicate that significant gastric mucosal ischemia can occur and may represent a mechanism in the development of gastric erosions in endotoxemia, even in the absence of systemic hypotension.


[E. coli enterotoxicosis in unweaned piglets. I. Some concepts (author's transl)]. In a brief review, attention is drawn to a number of findings on infections with enteropathogenic E. coli in suckling piglets: serological typinge K88 antigen, colonisation, enterotoxin production and enterosorption, absence of symptoms of inflammation in the bowel wall and significance of the various immunoglobulin classes. The term E. coli enterotoxicosis used to designate the disease is preferred to terms such as E. coli diarrhoea, E. coli enteritis and (enterotoxic) colibacillosis.


[E. coli enterotoxicosis in unweaned piglets. II. Preparation and preventive administration of immunoglobulins (author's transl)]. Laboratory and field trials were made of an immunoglobulin prepared from sows hyperimmunized with E. coli O149:K91,K88. Of the three methods of inoculation (oral, intramuscular and intraperitoneal) used in laboratory trials in specific pathogen-free (SPF) piglets, oral administration was found to result in the lowest concentration of immunoglobulin in the serum of the piglets. There was little difference between the concentration of immunoglobulin in the serum of the piglets following intramuscular administration and that following intrperitoneal administration. Oral and intraperitoneal inoculation of preparations of immunoglobulin were adopted in three herds in which enterotoxaemia caused by E. coli O149:K91,K88 was a recurrent problem. It can be concluded from these experiments that administration of immunoglobulins does offer some, but definitely inadequate, protection as a preventive measure in enterotoxaemia due to E. coli.


[E. coli enterotoxicosis in unweaned piglets. III. Preparation and use of vaccines in enterotoxaemia due to E. coli in newborn piglets in the Netherlands]. The preparation of a number of E. coli vaccines designed to prevent enterotoxicosis due to E. coli in young piglets is discussed. The results of laboratory experiments concerned with the production of haemagglutinating antibodies in pigs following inoculation of this vaccine are reported. This oil-adjuvant vaccine (OAV) was used in the field in thirty-one herds in which enterotoxicosis due to E. coli was a recurrent problem. It is concluded from serological and clinical observations that the use of this vaccine is advisable on farms on which enterotoxicosis due to E. coli occurs in young piglets.


[E. coli enterotoxicosis in unweaned piglets. IV. Evaluation of results obtained on using an adjuvant vaccine in the field (author's transl)]. The results obtained on using an adjuvant vaccine against enterotoxaemia caused by E. coli in suckling piglets are discussed on the basis of an inquiry conducted among a number of veterinary practitioners. The vaccine contains the OK groups O138:K81,K88, O141:K85ab and O149:K91,K88 and is administered parenterally to the dams during the latter half of gestation. The inquiry which covered 4,000 sows on fifty-five farms showed that, as regards diarrhoea during the first week of life, morbidity in the offspring of vaccinated sows decreased from 83 per cent to 6 per cent and that mortality dropped from 23 per cent to 0.3 per cent. Clinical results were slightly less satisfactory where diarrhoea during the second and third weeks of life was concerned. The importance of serological typing prior to vaccination is stressed. Abortion occurred in 0.5 per cent of the vaccinated sows within three days after vaccination. The question is raised whether there is a relationship between this vaccination and abortion.


Pharmacologic analysis of positive chronotropic and inotropic responses to octopamine. Effects of octopamine on sinus rate and atrial contractility were investigated using the isolated atrium preparation of the dog which perfused with heparinized arterial blood led from a support dog. When octopamine, dopamine or norepinephrine was administered into the cannulated sinus node artery, positive chronotropic and inotropic responses were dose-relatedly induced from 0.1 mug, 0.1 mug or 0.01 mug, respectively. The D.R.50 values (dose ratio at 50% maximum response) of octopamine, dopamine and norepinephrine are roughly 30-100: 30:1, respectively. The duration of action of octopamine was longest. Effects induced by octopamine were blocked by an adrenergic beta-blocking agent, alprenolol. Desmethyl-imipramine treatment significantly suppressed octopamine-induced effects but rather enhanced norepinephrine-induced ones. Octopamine-induced effects were not influenced by tetrodotoxin which blocked those induced by nicotine. From these results, it is concluded that positive chronotropic and inotropic responses to octopamine are mainly due to a tyramine-like action.


Dynamic changes of serum LH and FSH during pregnancy and puerperium. Changes of serum LH (HCG) and FSH, and their response to LH-RH during pregnancy and puerperium were studied by radioimmunoassay. There was little change in serum FSH level due to progression of pregnancy, and the serum FSH level of pregnant women was almost unchanged after injection of LH-RH. Serum LH (HCG) which decreased rapidly after delivery returned at about 15 days after parturition, and FSH which remained at a low level during pregnancy returned to the levels in the follicular phase of the normal women at about 20 days after delivery. The alteration in the response to LH-RH in puerperal period was as follows: First FSH began to respond about 10 days after delivery, and one month after parturition both LH and FSH showed remarkable response in comparison with that in the normal non-pregnant period. Beyond the second postpartal month, the response of FSH returned to approximately the same level as that in the normal non-pregnant period, but the response of LH was still marked when compared with that in the non-pregnant period. There were no differences in the response to LH-RH between the nursing and non-nursing women.


Histamine changes in Plasmodium falciparum malaria. Histamine, serum complement factor 3 (C'3) and platelets were studied in 33 Plasmodium falciparum patients. Elevation of histamine level in the blood was found during acute infection but was more marked in the group of patients with systemic complications. A correlation between histamine changes, clinical complications, reduction of C'3 and degree of thrombocytopenia was observed. The possible role of histamine in the development of complications in P. falciparum infection and the possible release of this substance through the activation of complement system and immune destruction of platelets were discussed.


XIII. Cerebral circulation and metabolism in stroke. Cerebral circulation and metabolism in stroke study group. An understanding of the cerebral circulation is so fundamental to comprehension of the pathogenesis of stroke that cerebral blood flow and metabolism merit review in this series of reports. The authors recognize that the research described here is very technical in nature and may appear to have little practical application to clinical medicine. Nevertheless, these matters are basic to the development of precise methods for the measurement of regional cerebral blood flow in man which could be used to monitor the therapy of stroke with greater success than is possible at present.


[Cellular immunity in two familial cases of thyroid carcinoma (author's transl)]. Cellular immunity in two brothers with thyroid carcinoma in a family presenting pathological thyroid changes is investigated. In these brothers a low PHA lymphocyte blast-transformation and an elevated number of surface membrane Ig bearing lymphocytes were observed. These data are discussed in relation to the question of immunological defects which frequently are present in carcinoma patients.


Adjustable nonimplantable electrical stimulators for correction of urinary incontinence. Investigations of functional electrical stimulation (FES) of the closing muscles in the lower urinary tract using nonimplantable electrical stimulators have reached the final stage. The optimal stimuli parameters were chosen on the basis of neurophysiological studies of the urinary tract and urodynamic measurements of mechanical response to electrical stimulation. According to these findings, two electronic systems for FES have been developed. An adjustable system for stimulation of the urethral closing mechanism using vaginal or anal plugs. The external unit of the stimulator contains a generator producing square-wave pulses. The vaginal and anal plugs are from Vitalograph Ltd, and Cardiac Recorders Ltd., commercial tipes redesigned to suit our needs. Frequency and duration of the pulses can be individually adjusted for each patient. An automatic integrated adjustable system for stimulation of the urethral closing mechanism built into a vaginal plug. This stimulator is based on completely new design principles. It has the form of a cylinder with hemispherical ends. Both the electronic unit and battery supply are located within. The system is completely automatic and is started by placing the stimulator in the vagina. Both systems mentioned were constructed for curing stress incontinence, post-operative incontinence, enuresis and in some cases for use in incontinent paraplegics. Clinical evaluation has given satisfactory results for both types of stimulators in the above-mentioned patients. They are simple to use and instructions can be given in an urologist's prescription. Permanent or intermittent application is possible.


EMG-patterns of pelvic floor muscles with surface electrodes. On reviewing the literature most authors were found to have used needle electrodes for recording muscle potentials of pelvic floor muscles. We used for the first time a vaginal tampon electrode to record potentials of musculus levator ani in females and the same electrode to record potentials of the external anal sphincter. Recording with surface electrodes is especially recommendable for repetitive investigations for follow-up studies in outpatients and children. EMG patterns of pelvic floor muscles with vaginal tampon electrodes are comparable with those derived by needle electrode. EMG criteria of diagrams in upper motor neuron lesion, lower motor neuron lesion and with irritable bladders are discussed and explained.


[The treatment of locally confined prostatic carcinoma: radiotherapy versus total prostatectomy (author's transl)]. Recent data show that carcinoma of the prostate is not radioresistant. But not all prostatic cancers are radiosensitive. All information available in the literature on histologically proven local destruction of prostatic cancer tissue, all survival data and reported complications after radiation treatment are reviewed and discussed. The results of radical surgical treatment from various authors but mainly from the series of Belt and Schröder are used for comparison. From these data it is evident that total prostatectomy of stage B and C tumors is superior to radiation therapy as far as local eradication of tumor goes. Five- and ten-year actuarial survival rates are about identical for stage B disease but favor total prostatectomy in stage C patients. Sexual impotence, the most important lasting complication of total prostatectomy, is present in 23-47% of patients after radiotherapy. Urinary incontinence is not known after irradiation but reported after surgery. Long term damage of the lower urinary tract, the gastrointestinal system, or the lymphatics was reported in 2-24% of patients after radiotherapy. The indication for radiation treatment in stage D patients is very questionable. Exact surgical staging by iliac and obturator lymphadenectomy is desirable to rule out stage D disease in locally confined tumors. Radiation treatment is indicated in patients who are not willing to undergo surgery, who are unwilling to accept sexual impotence, or who are poor candidates for surgery from other reasons.


Aggressive management of genitourinary complications of renal transplantation. In the course of 184 renal transplantations performed in St. Louis since 1963, twenty-six minor and twenty-three major complications have occurred. As a result of these complications four kidneys have been lost and 1 patient has died. Aggressive therapy has been utilized in the management of all but two of the major complications and is associated with one death and the loss of two kidneys. On the basis of these results intensive therapy for genitourinary complications is encouraged, and the principles of therapy are discussed.


Emergency cadaveric donor en bloc nephrectomy by in-corpora perfusion technique. A rapid and safe technique of donor nephrectomy using in-corpora perfusion is described. This technique has the advantages of minimizing the warm ischemic time, avoiding damage to the accessory renal arteries, as well as providing aortic cuffs for small pediatric donor renal arteries.


Abnormalities of bladder innervation in diabetes mellitus. Electrophysiologic evaluation of the neural pathways involved in bladder and urethral function is described in 30 patients with diabetes mellitus. The study showed decreased conduction velocities in patients with the detrusor reflex as well as in detrusor areflexia. The findings indicated that diabetic vesical dysfunction is principally the result of segmental demyelination in the peripheral nerve supply to the detrusor muscle and urethra.


Prevention of lethal pseudomonas bacteremia with epimerase-deficient E. coli antiserum. All of these experiments demonstrate that despite many microbiologic differences between Pseudomonas and the enteric rods, there is a close immunologic relationship between their endotoxin cores. These studies also show that by genetic manipulation we can unmask a protective antigen for preparing antiserum with a broad range of activity, even in the face of neutropenia. Production of potent human J5 antiserum is a safe, simple procedure, making it possible to consider endotoxin core antibody treatment of all Gram negative bacteremia in patients regardless of the causative organism.


[Stimulating effect of autotransplantation of preserved bone marrow on hematopoiesis]. In a given communication, the results of transplantation of autologous bone marrow, preserved at -50 degrees in the medium 199, added 10% low-molecular polyvinylpyrrolidone, are reported. Fourty two patients with pulmonary cancer of stage III and IV after pathohistological studies were subjected to chemoradiation therapy. The study of peripheral blood, the sternum and iliac bone needle biopsy specimens following this therapy has evidenced an inhibition of bone marrow hemopoiesis and of megakaryocytic growth, in particular. Autotransplantation of the preserved bone marrow against the background of inhibited hemopoiesis results in a nearly complete restoration of the bone marrow hemopoiesis.


[Primary multiple tumors in women treated for cancer of the cervix uteri]. Observations of primary multiple tumors in patients with cervical cancer, treated during the period of 1946--1970, are analysed. It was found that the number of patients with multiple tumors increased considerably as compared with the period of 1926--1947. Most frequently, the second malignant tumor was observed in the internal genitalia, mammary gland and digestive tract.


[Clinical trial of the preparation Caved S in treating peptic ulcer]. The observations upon the therapeutic effect of Caved S preparation are reported, being a combination of deglycyrrhizinated liquorice, alkalizing substances and vagolytic drugs. The clinical trial of the medicine reveals it to be with a quick effect on  the subjective complaints good tolerance and no manifested disturbances on water and electrolyte balance. It is suitable for the treatment of patients with gastric and duodenal ulcers. Ulcer niche roentgenologically is healed in 37,5% of the patients with gastric ulcer and in 33% in the patients with duodenal ulcer. Endoscopically, the niche is healed in 25% of the patients with gastric ulcer and in 28,5%--with duodenal ulcer. The medicine is with no effect in cases of gastric callous ulcer, as well as with pyloric stenosis.


[Clinical trial of the Bulgarian digitalis preparation, Digilanide C used intravenously]. The Bulgarian digitalis preparation Digilanid C for venous application has a satisc factory effect on the majority of the patients (67 per cent) with light and moderate chronic cardia insufficiency and espically in case of tachycardia in auricular fibrillation. The comparison of the results between the group of 46 patients, treated with Digilanid C and the control group of 20 patients treated with Isolanid (Richter) do not reveal essential differences in the major part of the results obtained.


[Clinical studies of beta-methyl-digoxin in patients with cardiac decompensation]. The results are reported from the observations on the activity of the semi-synthetic preparation beta-Methyl-Digoxin in 60 patients with chronic cardiac insufficiency. The conclusions are based on the data, obtained by a series of clinical and instrumental examinations, electro- and balistocardiography included, measurements of venous pressure, etc. The high efficiency and good tolerance of the preparation is stressed upon. It is stressed to be especially suitable for the treatment of patients with bradycardic form of chronic heart decompensation as well as in the treatment of cardiac cirrhosis.


[Comparative clinical studies of the effectiveness of the most frequently used antibiotics in the period of 1961-1970]. The results from the treatment of 1086 patients, treated at the Therapeutic Clinic, HMI- Sofia were followed up for the period 1961-1970 incld. Acute bacterial and vuris-bacterial pneumonias were found in 318 patients, 475 of the patients were with exacerbated chronic bronchitis and bronchiectasis, with exacerbated chronic pyelo-nephritis -216 patients and with exacerbated chronic cholecystitis and cholangiohepatitis --92 patients. The effect of the treatment was determined according to a three-stage scale "good" with complete clinical healing (in acute pneumonia), with "improvement"--with complete clinical remission (in chronic infections) and "without effect". Clinical and paraclinical indices were used as criteria in the determination of the effectiveness. The data are statistically processed according to the method of variation analysis. In patients with acute pneumonia the- best effectiveness was manifested by tetraolean (88,7 per cent), tetracylins (77,8 per cent), chloramphenicol (76,8 per cent), penicillin (72,5 per cent), the combination penicillin-streptomycin (71,9 per cent); in patients with exacerbated chronic bronchitis--tetraolean (88,0 per cent), chloramphenicol (73,2 per cent), tetracylins (65,3 per cent); in patients with exacerbated chronic pyelonephritis - chloramphenicol (65,5 per cent); in patients with exacerbated chronic cholecystitis and cholecysto-cholangiohepatitis-tetraolean (70,7 per cent), tetracyclins (66,7 per cent), chloramphenicol (66,1 per cent).


[Clinical evaluation of tetraaolean: comparative studies with tetracycline]. The results from the comparative clinical studies on the effectiveness of tetraolean and tetracycline are summed up about 1672 patients with acute and exacerbated infections of the respiratory organs (1036 patient, treated by ten teams, working on the theme given in advance "Comparative clinical studies between tetraolean and tetracyclin in acute pneumonia", 164 patients with postgrippe viral-bacterial pneumonia, treated during the grippe epidemy 1972/1973 and 445 patient treated at the Therapeutic Clinic, Sofia during 1967-1972). The total results reveal that, according to the adopted objective indices, the therapeutic effect of tetraolean is with a statistically significant superiority over tetracyclin. The beneficial results obtained in the treatment of 14 patients with endocarditis lenta are also reported. The mechanisms of that superior effect, defined as "clinical synergism" are discussed.


Gallstones.

Gallstones. Cholesterol saturation of bile has a primary role in the pathogenesis of gallstone formation. Predisposing factors should be considered. The characteristic features of biliary colic are important to keep in mind, as well as the fact that a history of fatty food intolerance is not of value in the diagnosis of gallstones. The technique of endoscopic retrograde cholangiography is useful for the diagnosis of bile duct stones in jaundiced patients and in patients with a strong clinical history, but in whom findings on oral and intravenous cholangiograms are within normal limits. Improved techniques of operative cholangiography to diminish the incidence of retained gallstones have been developed. Also, choledochoscopy provides a remarkable technique for diagnosis and choledocholithotomy. The dissolution of gallstones with chenodeoxycholic acid is an experimental procedure. This bile acid is thought to act by increasing the chenodeoxycholic acid pool size and decreasing cholesterol synthesis and secretion, thereby reversing the defects responsible for gallstone formation.


[Diabetes mellitus and control of protein biosynthesis in rat liver (author's transl)]. Protein synthesis of liver risobosmes is markedly reduced in diabetes mellitus. This finding is well correlated with the protein catabolic state of insulin deficiency in general and with the reduction of protein synthesis by muscle ribosomes in particular. However, with regard to the mechanism of the amino acid incorporation by muscle ribosomes there is indication for an additional participation of transcription in the diabetes-induced reduction of protein synthesis by liver ribosomes. There is support for the hypothesis of an additional effect of diabetes on ribosomal wash proteins and on synthesis of ribosomal ribonucleic acids with consecutive reduction of conformation of ribosomal subunits or binding of ribosomal subunits to template RNA respectively.


[Problems of infections following renal transplantation (author's transl)]. Infections arising as a complication of immunosuppressive therapy were analyzed in more than 40 renal transplant patients. Bacterial infections were observed in 78.0%, viral in 68.3% and mycotic infections in 56.3% of cases seen during a 3-year investigation. Infection was the cause of death in 5 out of 8 cases with fatal complications. Bacterial infections of the lungs were amongst the gravest post-transplant complications. Hepatitis B, herpes simplex and cytomegalovirus were the most common viral infections. Simultaneous bacterial, viral and Candida albicans infections--so-called "triple infections"--with a very poor prognosis were diagnosed in 25% of the investigated cases. The data show that after cadaveric kidney transplantation special emphasis should be laid on careful prophylaxis of infections and diagnostic measures for the early recognition of possible infections arising as a complication of immunosuppressive therapy.


[Historical report on the situation of the "fight against tuberculosis" in the town of Halle, Germany, 1899 (author's transl)]. In 1896 the so-called "Department X" of the "Association for Public Welfare" was founded and turned to be the first organisation of the "fight against consumption" in the town of Halle. Under the guidance of PUTTER and REINEBOTH a first dispensary for tuberculous patients was established and became the prototype of similar institutions in Germany and other countries.


[Immunopathological phenomenona in liver diseases]. More than 400 patients with acute and chronic liver diseases as well as non-hepatic diseases (control group) were examined for the existence of antibodies against mitochondria, smooth musculature and cytoblasts with the help of the immunofluorescence-serological method. The proof of the hepatitis-B antigen was carried out by means of the transmigration-electrophoresis. Auto-antibodytitres larger than 1 : 160 (limiting titres) could be established only in the chronically aggressive hepatitides and the chronically destructing non-purulent cholangitides. Whilst in the chronically destructing non-purulent cholangitides dominate high mitochondrial antibody-titres, in the chronically aggressive hepatitides the antibodies against smooth musculature and/or cytoblasts are dominating. When the hepatitis-B-antigen was present in all groups of diagnosis auto-antibody titres of 1 : 160 were not transgressed. The kind of the antibody-spectrum and the size of the antibody-titres seem to be suitable for the differential diagnosis. High mitochondrial antibody-titres in women are suspicious of a chronically destructing non-purulent cholangitis. High titres of antinuclear antibodies or such ones against smooth musculature might be a reference to the so-called auto-immune form of the chronically aggressive hepatitis. For a still better differentiation of the chronic liver diseases the determination of these antibodies seems to be valuable.


[Immunodiagnostic methods in lupus erythematosus disseminatus]. In 27 patients with lupus erythematodes diseminatus the determinations of the LE-cells according to the macromethod (Zimmer and Hargraves) and the micromethod (Mudrik and co-workers) were compared with the demonstration of antinuclear factors according to the indirect immunofluorescence and immune enzyme technique. The sensitiveness of the two last-mentioned immunomorphological methods is somewhat larger. In these cases the size of the titre of the antinuclear factor almost always correlates positively with the number of the LE-cells. For the purpose of the initial diagnostics and the judgment of the course a morphological method cannot be renounced, since in the acute episode a high consumption of the antinuclear factor the immunological methods negatively correlate with the number of the LE-cells. The immune enzyme technique is to be recommended on account of the smaller expenditure, permanence of the preparations and high sensitiveness as alternative method of the immunofluorescence technique. In the micromethod the large variation is opposite to the advantage of the slight quantity of blood and to an always existing evaluability. Investigations of the lymphocytes of patients with lupus erythematodes disseminatus by means of the lymphocyte transformation test and the determination of the B-cells with the help of the direct immune peroxidase technique refer to the close pathogenetic connections of cellular and humoral immune reactions in this disease.


[Technic for the presentation and evaluation of pathognostically significant erythrocyte changes]. In this paper is described in all details a method of staining and evaluation of blood smears which was originally proposed by Clara Fonti and was revised by the authors. With the help of this method characteristic changes of the erythrocytes can be demonstrated. The changes are depending on growth processes. Without exception they appear in an increased range in the growth of malignant tumours.


[Progress in pancreatic X-ray diagnosis in the last 30 years]. Proceeding from the pre-war state of the radiology of the pancreas in temporary order those investigations are discussed which essentially furthered the diagnosis of pancreatic diseases. The pneumopancreatotomography allowed the first direct proof of the pancreas; it has essentially enriched the anatomic conceptions. 10 to 15 years ago the splenoportography was the most evident examination of vessels. Today it is substituted by the coeliaco-mesentericography which in the venous phase delivers a splenoportogram and which allows to prove tumours rich in vessels with sufficient certainty. The investigation of the duodenum in hypotension improves the diagnostic of space-demanding processes on the surface of the head of the pancreas. The main value of scintigraphy consists in the exclusion of pancreatic diseases. The main value of scintigraphy consists in the exclusion of pancreatic diseases. The endoscopic retrograde cholangio-pancreaticography allows to shift the operative phase into the preoperative phase. Trijodated contrast remedies and developments concerning the technics of the apparatuses resulted in essential advantages. The pancreatic space which was empty 30 years ago is very much detected nowadays, though a contrast remedy which can be secreted by the pancreas needs still the detection.


[Breath-analysis tests in gastroenetrological diagnosis]. The introduction of a simple method for analysis of 14CO2 in breath allowed a more widely application of breath-tests in the diagnosis of gastroenterological diseases. During a breath-test a 14C-labelled compound is administered orally and 14CO2 is subsequently measured in breath by discontinuous samplings of 14CO2 by virtue of a trapping solution (hyamine hydroxide). Most helpful tests in gastroenterology are the 14C-glycyl-cholate breath test for detecting increased deconjugation of bile acids due to small intestinal bacterial overgrowth or bile acid malabsorption in ileal resection or Crohn's disease of the ileum, the 14C-lactose breath test in lactase deficiency, whereas the 14C-tripalmitin test seems less helpful in the diagnosis of fat malabsorption. A 14C-aminopyrine breath test may turn out to be a simple and valuable liver function test. Oral loading tests with breath analysis of H2 have shown to be helpful in the diagnosis of carbohydrate malabsorption, determination of intestinal transit time and intestinal gas production. Due to technical reasons (gas-chromatographie analysis) H2-breath analysis is still limited to research centers. Despite low radiation doses after oral administration of 14C-labelled compounds oral loading tests with H2- or 13C-analysis might be preferable in the future.


[Hormonal limitation of lactation (author's transl)]. A doubleblind study comparing the limitation of lactation and absence of side effects of the oral estrogen Quinestrol with an injected drug. The main point was limitation of lactation immediately following delivery up to the first period. Table 1 shows an analysis of results. The oral drug was better and called "very good" only in the immediate postpartum time. There was no significant difference in the second phase up to the first postpartum period. The interval between delivery and first period was 8 - 9 weeks s. table 2. There was no difference in the intensity of the first perio" s. table 3.


Antenatal diagnosis by means of ultrasound in the rare case of foetal parasitic tumor. A case of hydramnion is presented. Antenatal diagnosis of a tumor in the sacral region of the foetus was made by means of ultrasound, while the roentgen investigation gave a negative result. Postnatal confirmation of the ultrasound diagnosis was subsequently obtained and a detailed patho-histological description of an abnormal foetus is given.


[A simple method for measuring the surface areas of membranes in histology demonstrated on the calf hypophysis]. The work carried out with the hypophysis of three calves to demonstrate that a sharp border line does not exist between Adeno- and Neurohypophysis. The result of these experiments show that on the average 57,1% of border line is of connective tissure and the remaining area lacks this type of membrane. In the border area lacking connective tissue, basophil Adeno-Hypophysis cells play an important role in transporting the secretion from Adeno- to Neurohypophysis. The basophil infiltration in the pars posterior are in the form of spread branches which could distinctly be seen; The infiltrating cells are in group or in the form of solid line rather than the isolated form, while the single cells could be noticed around the formers. These cells penetrate only a short distance in Neurohypophysis. The basophil Adenohypophysis cells lose their shape and original charakteristic gradually as they farther infiltrate in, and finally dissolved and considered as a holocrine secretion.


[Polysaccharide additives in foods rich in proteins. i Sample preparation for estimation, especially in fresh cheese (author's transl)]. Published procedures for the isolation of polysaccharides from foods rich in proteins, especially fresh cheese, proved not very useful for the concentration in question (0,01--0.2%). We, instead, propose the following sample preparation: 1. Removal of lipids by an ethanol--ethyl ether--petrol ether mixture; 2. complete hydrolysis of proteins with pepsin, pronase E and a mixture of aminopeptidase M and prolidase; 3. separation of the polysaccharides from the low molecular substances and from enzyme residues by gel filtration on Biogel P-2; 4. concentration of the polysaccharides containing fraction by freeze drying, ultrafiltration or evaporation. --The method was tested with quarg and double cream fresh cheese, it can, however, be adopted to use in other products.


A modification of anti-streptolysin-O-test. In this short communication, we have suggested a simple and economic method of performing ASOT. It is a simpler method than that previously recommended by the Wellcome Reagents Limited, in their pamphlet. It requires only 0.05 ml. of the patient's serum and also smaller quantities of all reagents. This reduces the cost of each investigation considerably.


[Evaluation of phenylalkanoic acid derivatives in the management of rheumatic diseases as well as various explanations on the doctrine of clinical research technics]. The pharmacology and toxicology of the phenylalkanoic derivatives are discussed with particular reference to Ibuprofen. Clinical trials of Ibuprofen are reviewed and their methodology assessed. A more rational approach to anti-inflammatory drug evaluation is suggested and the need for closer international co-operation in establishing a standardized approach to clinical trial methodology is emphasised.


[Guidelines for synovial cytology].

[Guidelines for synovial cytology]. Certain technical requirements have to be satisfied when synovial fluid is submitted for evaluation. This is to enable examination of the cell morphology and the polysaccharide and lipoid histochemistry of the cells and the dried liquid phase. The cell physiology should be considered when evaluating the cytogramme. Morphological and histochemical examination of the background indicate which biochemical estimations of the liquid phase are needed, and thus represent added diagnostic tools for evaluation of joint diseases. Cytolysis, cell involution and substrate condensation are discussed in detail.


[Studies on the influence of psychological factors on the immune system: the result of infantile stimulation on the disease course in neonatal mice with bacterial infection]. NMRI mice of both sexes were, from the first to the tenth day of life, either stimulated by means of handling, or sensorically, or not stimulated at all (the control group). On the tenth day of life, they were separated from their mothers, inoculated intraperitoneally with E.coli O 111 and subsequently subjected to a total deprivation of food and water. The handling-group animals died significantly (1% level) faster than did the sensorically stimulated and the non-treated control group animals. No significant differences could be found in the mortality rates of the last two mentioned groups. After subdividing the animals into five weight classes, a comparative analysis of the three groups showed that the differences in mortality were independent of body weight. The significance of these first animal experiment data on the influence of early experience on the course of infectious diseases in childhood is discussed.


[Sanitary-index significance of enterococci in the study of household articles]. A total of 670 washings from various household articles were studied in creches and kindergartens for fecal contamination with the aid of two bacteriological tests (coli and enterococal titres); the degree of their contamination with enterococci and E. coli differed. Strongly contaminated objects (diapers, swaddling tables) were revealed with equal frequency by both tests, but objects assessed as moderately contaminated were more frequently revealed by the enterococcus test (P less than 0.05) than by colimetry. Criteria of evaluation of the quality of washings by the data of enterococcometry are suggested.


[New principles for obtaining protective antigens from deep cutlures of enterobacteria]. A model of S. typhi submerged culture was used; application of the principle of sparing extraction of surface protective antigens by the action of sublethal concentrations of two damaging agents differing by the mechanism of inhibition of the processes of vital activity of the microorganisms was founded. The principle is based on regularities characteristic of cells of bacterial pupulations: a) nonhomogeneity of individual cells of the population by the resistance to the damaging agents, and b) independence of distribution in the population cells of resistance to different damaging agents. The following typhoid antigens were obtained by combined action of sublethal concentrations of hydrogen peroxide (0.25%) and formalin (0.1%): antigens with a full antigenic structure (inducing formation of O-, Vi- and H-antibodies), of low toxicity (V50  - 0.65+/-19 mg) and highly immunogenic (AU50- 0.45+/-0.25 mug) in experiments on mice.


[Study of mutants of Salmonella typhimurium with altered sensitivity to the antibiotic fusidin]. S. typhimurium mutants with altered sensitivity to fusidic acid (more resistant or more sensitive than the original culture) were selected. The mutants studied changed some of their properties (morphology, antigenic structure, and biochemical activity). They were characterized by a lower growth rate and probably by some alterations in the envelope cell structures- Some mutants acquired cross resistance or sensitivity to other antibiotics. As the mutants were selected by increased resistance or sensitivity to fusidic acid which affected the translocation factor G of the ribosome cycle, such pleiotropic changes of their properties could be due to some alterations in the G-factor itself.


[So-called mucoid forms of vibrio cholerae]. The authors present materials indicating that examination of nonagglutinating vibrios in the agglutination reaction with cholera sera after boiling, according to Sakazaki recommendation (1971), did not provide recognition of mucoid forms of cholera vibrio and its differentiation from cholera-like vibrios of other serological groups. It is suggested that one should take into consideration morphological peculiarities of the culture, stability of agglutination with cholera O-serum and the results of reaction of antibody adsorption in identification of cholera vibrios in the mucoid form.


[Data on the identification of staphylococci of hospital origin. Report 2. Method of biological typing of S. epidermis]. In accordance with the principles of numerical taxonomy the authors elaborated a new method of biological typing of S. epidermidis strains of hospital origin based on the use of 5 tests (gelatinase, hemolysis, lecithinase, phosphatase, lysozyme). The suggested scheme includes 5 biotypes. In typing 690 S. epidermidis strains it was revealed that 47.5% belonged to biotype 1,14.4% - to type 2,11.2% - to type 3,7.7% - to type 4,14.5% - to type 5, and 4.7% were nontyping strains. The suggested scheme permitted better differentiation of the cultures under study than methods of biological typing suggested earlier by foreign authors. The new scheme requires wide approbation.


[The dynamics of the registration of neurosyphilis according to autopsy findings over a forty year period (1933-1972)]. The material of dissections obtained from 4 large mental hospitals of Moscow and the Kashchenko mental hospital speaks in favour of the fact that there is a steady drop and lethality from neurosyphilis, the absence of tabes dorsalis during the past 40 years, of meningo-encephalitis and of a significant reduction of cases with tabo-paralysis and brain gummas.


Polyglycolic acid (Dexon) versus silk for fascial closure of abdominal incisions. Suture-granulomas were previously found in 6% of patients subjected to colorectal surgery. It was therefore investigated whether the use of polyglycolic acid (Dexon) instead of silk for fascial closure of abdominal incisions would reduce the rate of granulomas without an accompanying increase in rate of wound dehiscences. The two sutures were evaluated in a triple blind, randomized trial, using the paired sample principle in patients subjected to elective gastrointestinal surgery. One gram of Pentrexyl powder was applied to the subfascial space in all the patients and the wounds  were examined 10 days, 1 and 3 months after the operations. The trial was terminated when a closed sequential analysis had shown a significantly higher rate of dehiscences after closure with silk (12/163) than after closure with polyglycolic acid (1/163). Seven patients had granulomas after silk and one after polyglycolic acid at that time. Postoperative wound infections occurred in 7 patients after silk and 8 after polyglycolic acid. It is concluced that the use of polyglycolic acid (Dexon) nearly eliminates the risk of suture-granulomas, without increasing the risk of wound dehiscences; on the contrary, the rate of dehiscences was lower after polyglycolic acid.


The effect of respiratory frequency on pulmonary function during artificial ventilation. A review. This is a review of previous studies on the effects of variations between 12 and 24 breaths per minute in ventilation frequency during artificial ventilation, minute ventilation being constant. The total material consisted of 66 healthy subjects investigated under anaesthesia with artificial ventilation and 43 patients investigated during prolonged respiratory treatment. An increase in ventilation frequency resulted in an increased ratio of dead space to tidal volume (VD/VT) and in diminished alveolar ventilation with a subsequent elevation of Paco2. The pressures in airways and alveoli were lowered. The dynamic compliance both of the lungs and of the chest wall was diminished and inspiratory resistance was slightly reduced. Intrapulmonary gas distribution was unaffected. Cardiac output was increased, as was venous admixture. Pao2 was slightly reduced. The more efficient gas exchange occurring at a low ventilation frequency makes this setting preferable in the treatment of patients with chronic obstructive lung disease, whereas a high ventilation frequency, by improving cardiac output, may be advantageous in patients with circulatory failure.


Clinical trial of piracetam in disorders of consciousness due to head injury. The authors first remind some toxicological and some pharmacological properties of piracetam (Nootropil), then present the results of a test giving evidence of the presence of this drug in the cerebrospinal fluid after intravenous administration to man. In a double blind study, the activity of piracetam is tested on 31 patients suffering from coma after head injury. Only 27 patients without intracranial space occupying lesions are taken into account. Methods and results are described. Piracetam, although showing no activity on mortality, improves the level of consciousness.


Microscopic observations on the interaction of heavy meromyosin-S-1 and actin in myofibrils. The binding of the proteolytic myosin fragment, HMM-S-1, to the non-overlapping part of actin filaments in intact myofibrils can be demonstrated under the phase contrast microscope as a contrast reversal of striation. The same effect can be seen on ghost myofibrils (after myosin extraction) where the whole length of the I-filaments is bare. HMM-S-1-loaded ghost myofibrils contracted upon addition of ATP in agrement with the recent report of Oplatka et al. (1974a, b) but under the same conditions ghost myofibrils not treated with HMM-S-1) also contracted. If the ghosts were prepared under conditions more favourable to myosin extraction, contraction became nil or negligible even when we loaded then ghosts with S-1. Thus we attribute the effect described by Oplatka's group to a small numer of residual myosin filaments in the ghosts.


Effect of CB 154 (2-bromo-alpha-ergocryptine) on paralysis agitans compared with Madopar in a double-blind, cross-over trial. Twenty patients with paralysis agitans took part in a double-blind, cross-over investigation of CB 154 (2-bromo-alpha-ergocryptine) and Madopar (L-Dopa + benserazid (a peripheral decarboxylase inhibitor), dose ratio 4:1). Each treatment phase lasted for 8 weeks. Modapar was found to be significantly superior to CB 154 in the treatment of the Parkinson state as a whole (Webster total score) and the individual symptoms of hypokinesia, rigidity and tremor. Compared with pretreatment score, CB 154 had a weak, but significant effect on tremor, but not on the Webster total score, hypokinesia and rigidity. The effect of CB 154, however, varied: four patients preferred CB 154 to Madopar on account of its satisfactory therapeutic effect and fewer side-effects ("on-off" phenomena, hyperkinesia, psychiatric complications); other patients showed neither therapeutic effect nor side-effects of CB 154, which in some cases may be related to too low a dose-level of CB 154 (median 30 mg daily, range 20-60 mg). In the four cases first mentioned which showed a good effect of CB 154, the ratio between the dose of CB 154 and the dose of L-Dopa (in Madopar) was 3.5-10 mg/100 mg, i.e. in certain cases it must be assumed that the maximum dose of CB 154 lies around 120 mg daily.


Short-term clinical trial of phopranolol in racemic form (Inderal), D-propranolol and placebo in migraine. Propranolol penetrates the blood brain barrier, whereas mainly the racemic form, Inderal, possesses beta-receptor blocking properties. A comparison between d-propranolol and Inderal might therefore indicate the relative importance of the beta blocking properties and possible "central" effects mediated by propranolol and of importance in migraine prophylaxis. The effects of propranolol in racemic form (Inderal) 40 mg q.i.d., d-propranolol 40 mg q.i.d. and placebo were compared in 20 migraine patients. Inderal as well as d-propranolol were significantly superior to placebo. Inderal seemed to be more effective than d-propranolol, but the difference was not statistically significant (P greater than 0.05). The results indicate that beta-receptor blocking properties, but possibly also properties other than the beta-blocking ones, may be of importance for the anti-migraine effect of propranolol.


Clonidine (Catapresan)-double-blind study after long-term treatment with the drug in migraine. A double-blind, cross-over study with clonidine (Catapresan) and placebo was carried out in 29 patients with migraine, who had received clonidine during a 4 to 32 months pre-test period (mean 10 months) and who appeared to have benefited from the treatment. Clonidine and placebo were given for 7 weeks each, but only the last 5 weeks in each period were used for the statistical evaluation. In the entire material, clonidine was significantly superior to placebo. In nine of the patients, however, various other factors might have influenced the attack frequency and severity. If these nine patients were excluded, no statistically significant difference between clonidine and placebo was found.


Localization of phenobarbital in mouse central system by immunofluorescence. Utilizing antibarbiturate serum in an indirect immunofluorescence system, phenobarbital has been detected in the central nervous system of mice given an overdose of drugs. Localizaiton was primarily within neurons of the limbic system, caudate nucleus, cerebellum, cervical spinal cord and trigeminal ganglion. The technic may be of value in acquiring additional information about the barbiturates as well as being of value to the forensic pathologist.


Computer tomography of the brain in multiple sclerosis. A radiological study of 110 patients with special reference to demonstration of cerebral plaques. The brains of 110 patients with multiple sclerosis (MS) were examined by computer tomography (CT) with the fine matrix EMI scanner. In 41 cases (37 per cent) areas of low X-ray attenuation were demonstrated with elective location in the white matter around the anterior and posterior horns of the lateral ventricles. These areas are postulated to represent the well-known large periventricular plaques in MS. Contrast enhancement provided no further informattion. Cerebral plaques were concomitant to ventricular enlargement and/or cortical atrophy. Cerebral atrophy without demonstration of plaques was found in 50 cases (45 per cent) and only 19 patients (17 per cent) had normal CT scans. No difference was demonstrated between duration of disease or age at onset in plaque cases, atrophy cases and patients with normal EMI scans. The postulate regarding the nature of the low absorption areas in CT still awaits the verdict of future brain autopsies.


Denture stomatitis. Effects of chlorhexidine and amphotericin B on the mycotic flora. In 100 patients with denture stomatitis cultures and direct smears were used to evaluate 5 treatments, including sucking of chlorhexidine, amphotericin B or placebo tablets combined with denture soaking in 0.2% chlorhexidine or water. After 14 days of treatment the amphotericin B lozenges had brought about a significant reduction in the quantity of fungus on the oral mucosa, whereas they barely affected the large amount present on the fitting surface of the upper denture. Denture immersion in chlorhexidine significantly reduced the number of organisms both on the mucous membrane and on the denture. It therefore seems at least as important to treat the denture as the patient in denture stomatitis. Fourteen days after withdrawal of the drugs the mycotic flora was largely re-established.


Denture stomatitis. The clinical effects of chlorhexidine and amphotericin B. The clinical effects of an antibacterial substance with antifungal activity (chlorhexidine) and specific antimycotic (amphotericin B) in denture stomatitis were studied in 100 patients. Five 14-day regimens of chlorhexidine, amphotericin B or placebo lozenges combined with denture immersion in 0.2% chlorhexidine or water were tested. The efficiency of amphotericin B and chlorhexidine was comparable. This indicates that chlorhexidine has a considerable antifungal effect in the oral cavity and, further, that fungi are the responsible micro-organism in denture stomatitis rather than bacteria. Chlorhexidine frequently discloured the dentures. A high incidence of local and general predisposing factors to denture stomatitis, as well as of relapse 14 days after treatment, was observed.


Occurrence of lymphocytotoxic lymphocytes and antibodies after corneal transplantation. Twentyfive recipients of penetrating corneal grafts were investigated for the presence in the peripheral blood of cytotoxic lymphocytes by the Direct Cell Mediated Lympholysis (Direct CML) test as well as for lymphocytotoxic antibodies. Eight patients presented a positive Direct CML. Six of these patients have shown clinical signs of graft rejection, while two patients had a clinically uncomplicated course. Only one of the 25 patients had lymphocytotoxic antibodies. This patient showed a negative Direct CML, and a clinically uncomplicated course.. The findings seem to imply that recipients of corneal grafts can be immunized by their grafts and that cytotoxic lymphocytes in peripheral blood appear frequently in those patients showing graft rejection.


The calcaneal osteotomy of Dwyer: an indication for Kiel bone. Kiel bone has been used with uniformly good results as a bone graft in 15 cases of Dwyer's calcaneal osteotomy. It is suggested that Kiel bone is indicated for this operation in preference to autogenous bone.


Peripheral nerve injuries of the upper extremity. Sensory return of 137 neurorrhaphies. The results of sensory recovery of 137 neurorrhaphies of the upper extremity in 96 patients are reviewed. There were 85 primary and 52 secondary repairs. Various factors influencing the results and an evaluation based on the 2-point discrimination test are presented. Secondary repair within 3 months in the hand area gives better results than primary repair.


[Reconstruction of the pharynx after pharyngectomy]. Forty-five patients in whom a pharyngo-laryngectomy was carried out are described; in 21, the pharynx was reconstructed by gastric transposition and in 24 by primary reconstruction with a medially based cased flap. Minor complications, such as stenosis and fistulae occurred more often after the skin flap operation and the stay of the patient in hospital in this group was considerably longer compared to those patients having the pharyngeal replacement with the transposed stomach. However, the two year survival after skin flap reconstruction was 50% as against only 10% after reconstruction with the stomach.


Retraction of the delto-pectoral flap. Clinical observations and the design of an experimental model. The human delto-pectoral flap retracts markedly across its breadth, but remains the same length after elevation. This unindirectional retraction declines with age. Flaps in a similar position on the pig running in the same direction behave in a similar fashion, suggesting that such flaps are a suitable animal model for the study of this property.


Intravesical transurethral electrotherapy in meningomyelocele patients. The results in 100 patients of intravesical transurethral electrotherapy in the treatment of bladder paresis and micturition defects due to meningomyelocele are reported. Positive results were attained in 71 patients. The method and the physiological development of controlled micturition are discussed.


Skulls with facial clefts. Experimental surgery on the facial skeleton. Skulls of adult, unoperated patients with facial clefts show additional anomalies specific for the type of cleft. In an experimental study we demonstrated that similar anomalies develop in rabbits with clefts that are artificially made in the fourth week after birth. Some surgical methods (Veau, primary osteoplasty) for correction of facial clefts are compared with regard to their effect upon later growth of the skull of young rabbits. The importance of experimental surgery preceding the introduction of new surgical techniques on the growing skull and its facial skeleton in particular is stressed.


Potency of purified tuberculin determined by the shock method on hamsters. Two lots of purified protein derivative of tuberculin with different potencies determined by skin tests on guinea pigs, were examined for their capacity to induce shock in hamsters sensitized with BCG. Groups of hamsters were injected with varying doses of a highly potent strain of BCG grown in Dubos fluid medium. 4-5 weeks later two groups of animals sensitized with corresponding doses were injected intraperitoneally with 1 mg of each lot of tuberculin. 12 of the 20 hamsters given the strong tuberculin died, while all those given the weak tuberculin survived. An attempt was made to evaluate the mutual potency of the two lots of tuberculin by injecting groups of sensitized animals with 1 mg strong or 4 mg weak tuberculin. The difference in the number of deaths from shock in the two groups was not significant.


The effect of phenylbutazone and chloramphenicol on phagocytosis of radiolabelled Candida albicans by human monocytes cultured in vitro. The effect of phenylbutazone and chloramphenicol on the function of blood monocytes cultured in vitro was studied. Both drugs had an inhibitory effect on the engulfment stage of phagocytosis. While a moderate effect only of chloramphenicol on digestion of engulfed yeast particles was found, phenylbutazone caused a marked reduction of the digestion of engulfed particles. Concomitant with this reduction of digestive ability, the lysosomes showed no morphological alterations as observed in control cultures without drug addition, indicating a lack of fusion between the engulged particles and lysosomes in the presence of phenylbutazone.


Isolation of C1q-binding immune complexes by affinity chromatography and desorption with a diaminoalkyl compound. The applicability of affinity chromatography to the isolation of C1q-binding immune complexes (IC) in sera was explored. Purified human C1q was covalently coupled to agarose or adsorbed to IgG-agarose resins. Sera containing preformed virus-antibody complexes or rheumatoid arthritis (RA) sera were passed through the columns and C1q-bound IC, eluted off with 1,4-diaminobutan at mild basic conditions, were analysed by immunodiffusion, crossed immunoelectrophoresis, gel filtration and electron microscopy. Under conditions of antibody treatment which caused almost 100% inhibition of virus plaque formation, about 30% of formed 14C-labelled equine arteritis virus-antibody complexes was bound specifically to and desorbed from C1q-IgG agarose columns. Studies with RA-sera indicated the presence of both IgM-IgI and intermediate size IgG, C1q-binding, complexes in 3 out of 5 tested seropositive sera. In two sera only intermediate size IC were demonstrable. The results obtained in these two IC model systems suggested that the described methods could be useful for isolation of C1q-binding IC in general.


Elimination of ingested 32P-labelled E. coli from rat polymorphonuclear neutrophils (PMN). Evaluation of a method. A method to be used for in vitro assay of the elimination of ingested 32P-labelled E. coli from rat PMN monolayers has been evaluated. The rate of expulsion of bacterial label from phagocytes into the extracellular medium was found to range between 40 and 50% of the total uptake 180 min after termination of ingestion. Serum enhanced the cellular uptake of bacteria, but did not affect the rate of elimination. Disintegration of the phagocytes was not found to be a problem.


Influence of hydrocortisone on uptake and elimination of 32P-labelled E. coli by rat polymorphonuclear neutrophils (PMN) in vitro. Hydrocortisone was tested for inhibition of uptake and of elimination of E. coli by monolayers of rat peritoneal PMN. 32P was used as label of the bacteria and their degradation products eliminated from the phagocytes. The cellular uptake was reduced by hydrocortisone (1-2 mg per ml) both in the presence and absence of serum, while the elimination of bacterial label was reduced by 0.5 mg per ml and higher concentrations of the drug.


Studies on the Treponema pallidum immobilizing activity in normal human serum. 2. Serum factors participating in the normal immobilization reaction. The T. pallidum immobilization reaction to be achieved by unheated normal serum was found to be complement dependent and the results presented suggested that complement was activated via the classical pathway. Besides complement, an immobilizing antibody of the IgM class was necessary for the immobilization reaction to occur. Lysozyme exerted an enhancing effect on the normal serum immobilization reaction.


Studies on the Treponema pallidum immobilizing activity in normal human serum. 3. The kinetics of immobilization reaction of normal and immune sera. The influence of immobilizing antibody, complement and lysozyme, on the T. pallidum immobilization reactions of normal and immune sera was studied. Lysozyme shortened the lag periods and increased the reaction rates of the reactions of normal and immune sera. At high concentrations of added lysozyme, variations in the concentrations of immobilizing antibody and complement, within a wide range, did not further influence the kinetics of the two reactions. Preincubation with lysozyme did not influence the treponemes in the following immune serum immobiliation reaction provided the lysozyme was removed before the addition of antibody and complement. Normal serum was found to immobilize T. pallidum more rapidly than immune serum. This was seen also if the reaction mixtures were almost identical, the only differences being the immobilizing IgM antibody involved in the normal and the IgG antibody involved in the immune serum reaction.


Interaction of streptococci with the Fc fragment of IgG. The capacity of human IgG to interact with beta-haemolytic streptococci was studied in order to localize the site of interaction on the IgG molecule. The reactivity of different proteolytic fragments of IgG with streptococci group A, type M 1 and type M 56, group C and group G, was investigated by measuring their inhibitory effect on the uptake of 125I labelled IgG myeloma protein by the streptococci. Equivalent molar amounts of Fc fragment and undigested IgG inhibited the uptake of 125I labelled IgG myeloma protein equally well while only slight inhibition was obtained by F(ab')2 preparations. No reactivity was found with IgM, Fab or chymotrypsin produced fragment Fc', of IgG. The reactivity of IgG with the streptococci was localized to the Fc fragment. Since the Fc' fragment was non-reactive, the CH2 domain was probably carrying the IgG structures involved in the interaction with streptococci.


Rat intestinal glycoprotein lowering bactericidal activity of serum on 32P-labelled E. coli. A glycoprotein fraction, by which the 32P-releasing activity of serum on labelled E. coli is lowered, was isolated from caecum content of germfree rats. The glycoprotein contained 83.1% sulphate, and 16.1% protein. The molecular weight ranged from 3.2 X 10(5) to 2.4 X 10(6), and the iso-electric point from pH 0.9 to 3.0. Physiologically, it may play a role in the interaction(s) between the host and its intestinal flora.


Photographic subtraction. II. Technical aspects and method. Technical aspects of photographic subtraction of original films in black and white and blue and white (Medichrome) under standard development conditions available in any roentgen unit are described. The adjustment necessary to control the gamma-value of the masking film takes advantage of the capacity of some graphic films to respond with different gamma-values on variation of the color of the exposure light.


Distribution of immunoglobulin-containing cells in human bone marrow and lymphoid tissues. Cell suspensions of human bone marrow, spleen, lymph nodes and palatine tonsils have been investigated for the presence of intracellular immunoglobulins by a direct immunofluorescence technique, using monospecific antisera against human Ig heavy chains alpha, mu and gamma and light chains kappa and lambda. Serum Ig levels were determined and the number of positive cells was compared with the concentration and calculated synthetic rate of serum Ig in each individual. The 28 patients studied covered a wide range of diagnoses and included those with normal as well as pathologically decreased or increased serum Ig levels. There was a high correlation between the calculated synthetic rate of each Ig class and the percentage of cells positive for the same Ig class in the bone marrow but not in the spleen, lymph nodes or tonsils. The Ig-containing cells constituted a much larger proportion of the total lymphoid cell population in the bone marrow than in the peripheral lymphoid organs. The estimated total number of Ig-containing cells was also much larger in the bone marrow than in the other organs investigated. It is concluded that in man the bone marrow is the major site of serum Ig synthesis and that the average synthetic rate per cell is the same regardless which of the three major Ig classes is produced. The role played by different lymphoid organs in humoral immunity is discussed in the light of the present results and reported data regarding lymphocyte and plasma cell kinetics in mammals.


Cellular events involved in the true primary immune response of splenocytes in vitro. An antibody response showing characteristics of a "true" primary response was readily induced in vitro with splenocytes from normal non-immunized animals cultured with strongly immunogenic Vibrio cholerae somatic antigens. Prior studies have shown that the response to vibrios in intact animals appeared to be a true primary response since no pre-existing antibody forming cells were present in non-immunized animals and the antigen induced response, following a lag of two days, resulted thereafter in a rapid stepwise increase in the number of specific PFCs, reaching a peak at 12 to 14 days. Using the Marbrook culture system for antibody formation a readily detected immunocyte response to vibrios was induced with splenocytes from normal non-immunized animals. No background antibody forming cells developed to the organisms without addition of vibrios in vitro. After in vitro immunization with 10(6) bacteria significant numbers of IgM PFCs appeared with a peak response on days 7 to 8. Splenocyte cultures from mice primed earlier with vibrios developed a marked secondary response, with appearance of both IgM and IgG PFCs. Large numbers of both classes of PFCs developed, with peak responses on days 6 to 7, similar to the "primary" response to sheep erythrocytes. However, significant numbers of PFCs to vibrios developed in cultures of vibrio-primed cultures even in the absence of vibrios during the 12 day culture period. The availability of a completely in vitro model system to induce a true primary immune response without the complication of pre-existing background antibody forming cells will be of value for further studies concerning various cellular pathways and interactions during the immune response to small amounts of strongly immunogenic bacterial antigens.


Regulation of immune balance by thymosin: potential role in the development of suppressor T-cells. Studies in a variety of animal and human models indicate that thymosin plays a role in the differentiation of a number of T-cell subpopulations. The hypothesis presented is that a normal immune balance depends heavily upon the presence of thymosin-activated suppressor or regulator T-cells. A major thrust in our present research program is to determine whether or not the various disorders discussed here are causally related to abnormal thymosin production by the thymus gland. We are also assessing in animal models the potential value of thymsin in the treatment of specific autoimmune diseases. This information may yield new insights for the management of autoimmune type disorders such as SLE. Results from clinical trials to date suggest that thymosin will have a role in boosting the immune responses of patients with specific thymic malfunctions and may indeed exert an influence via the production of suppressor or regulator T-cells.


Cell interaction in B/W mice: a reversible defect at the T-cell level. The anti-SRBC PFC response of old B/W mice can be restored by adding specifically activated T cells or primed spleen cells in vitro as well as by injecting LPS and SRBC in vivo. Since nonresponsive old B/W bone marrow and thymocytes cooperated in a normal manner upon adoptive transfer, this suggested that the lack of response to SRBC in the intact animal was due to a block in T cell activation and not due to intrinsic defects in lymphoid cells necessary to initiate a response. The block in T cell activation might be mediated by a suppressor cell found in old B/W spleens and it was hypothesized that this suppressor might also lead to a loss of self-tolerance.


Restriction by H-2 gene complex of the transfer of delayed type hypersensitivity in mice. Preliminary results suggest that the I-A region of the major histocompatibility complex restricts the ability of sensitized lymphoid cells to transfer a state of DTH to the specific antigen in normal mouse recipients.


The presence of cells expressing immune-complex receptors in non-lymphoid murine tumors. In this study we demonstrated that cells lodging in tumors have the capacity to fix antibody or immune complexes in vivo and in vitro. Although some of the fixation is probably by host, at least in one system studied, tumor cells, per se, were found to exhibit immune complex fixation.


Cell selection in the thymus of mice treated with escherichia coli lipopolysaccharide (LPS). The present data indicate that injection of LPS induces a decrease in thymus weight with selection of thymocytes more efficient in killer and helper activities. It has been reported (12) that two T-cell types may cooperate in the GVH reaction: the effector T1 and the amplifier T2. The maturation from T1 to T2 occurs mainly in the periphery, whereas immature cortex thymocytes differentiate to T1 within the thymus (13). Our results, showing an LPS-dependent enhancement of thymocyte killing activity, suggest that LPS selects thymocytes mostly of the T1 type. LPS-treated thymocytes are more efficient in the reconstitution of the anti-SRBC response. These data can be explained considering that LPS, like cortisone (14), enriches the thymus with more immunocompetent helper cells. Alternatively it may be suggested that LPS selects in the thymus cell populations characterized by high proliferative activity. Unpublished observations showing that LPS-treatment in vivo increases the in vitro response of thymocytes to Con-A are consistent with this interpretation.


Congenital hypoplastic anemia.

Congenital hypoplastic anemia. CHA, a rare failure of erythrogenesis in infancy and childhood, has been re-examined on the basis of a review of 42 cases of our own and 133 others. Although the disease may have its onset late in gestation, severe anemia usually is not found at birth but, in 75% of cases, becomes apparent within the first 4 months. Associated congenital anomalies include abnormal thumbs, webbed neck and growth retardation. Treatment with corticosteroids as soon as the diagnosis is established induces a remission in 80% of patients. Thereafter, this therapy may need to be continued, often at an extremely low dosage level, sometimes intermittently, for many years before the hemoglobin value maintains itself without medication. Spontaneous remission has occurred in a few cases after years of transfusions. Although it has long been considered that the disease was a failure of normal erythrogenesis manifest by a normocytic normochromic anemia, more exact measurements reveal that the anemia is macrocytic, with MCV usually ranging between 100 and 115 mu3. Other abnormalities of the red cells are present; in general, these resemble characteristics of fetal erythrocytes rather than normal adult cells. These red cell changes may persist even after the patient has been in remission for years, thus representing a permanent abnormality in erythrogenesis.


Mechanism of hypotensive effect during betaadrenergic blockade in hypertensive patients. The mechanism of the hypotensive effect during beta-adrenergic blockade in hypertension was studied in 38 patients with renal or essential hypertension using the new cardioselective beta blocker, Tenormin. During 5 weeks hospitalization the patients received first a placebo for 5 to 12 days, then a 75 mg. dose of Tenormin was given daily for 1 week, and thereafter the dose was doubled weekly as necessary up to 600 mg. daily. The blood pressure decreased from 180 +/- 26.2/118. "/- 13.6 mm. Hg on placebo to 151 +/-25.5/96 +/-13.8 mm. Hg during the final hospitalization period on Tenormin (600 mg. daily). Six patients developed fluid retention and as this occurred blood pressure control was lost. A subsequent follow-up on an outpatient basis of 15 of the patients showed that when the active drug was replaced by a placebo blood pressure rose again, confirming that the initial fall in blood pressure was a genuine effect. Multistage bicycle ergometer exercise tests were performed at weekly intervals to test the degree of beta blockade and indicated that this was nearly complete when a dose of 600 mg. per day was used. A significant correlation between the hypotensive effect and the degree of beta blockade, assessed by exercise tachycardia, was observed. A slight but statistically significant decrease (26 per cent) was observed in the plasma renin concentration, measured recumbent in the morning. This decrease was, however, not correlated with the hypotensive effect of the drug. Although the cardiac output decreased significantly (from 5.5 +/-1.7 to 4.3 +/- 1.1 L per minute, p less than 0.001), no correlation was found in individual patients between the cardiac output and the blood pressure decrease. On the other hand, for the total group of catheterized patients (n = 28) the calculated total peripheral resistance did not change significantly. Yet a significant correlation was found between the changes in total resistance and the hypotensive effect. This suggests that the reaction of the peripheral vessels rather than the cardiac output decrease determines whether the drug will produce a major decrease of blood pressure in patients with hypertension.


Evaluation of total IgE in diverse allergosis. Comparative study with other techniques. Part II. A total of 181 allergic patients were studied and classified according to the causal antigen, 92 patients were sensitized to the mixed grass pollen, 55 to house dust, 28 to Candida albicans, 31 patients with egg allergy and 25 with milk allergy. All of them presented strong positivity to anamnesis, intracutaneous tests and exposition tests. In all of them the serum total IgE was determined using the radioimmunoassay (RIST) and the antigen specific IgG, following Boyden's passive hemagglutination technique. In 31 patients with pollinosis, 55 with house dust allergy and 25 with sensitization to Candida albicans, the determination of the antigen specific IgG was also carried out following the quantitative precipitation method. The results showed a greater reliability on the hemagglutination as opposed to the determination of total IgE with grass pollen. The hemagglutination was positive in 90.20% and the total IgE was increased in 59.78% of the cases. In patients with house dust allergy the total IgE was elevated in 69.08% of the cases and the hemagglutination was increased in 60.71% of the cases. In those cases of sensitivity to Candida albicans, the total IgE presented higher values in 63.84% of the cases, while the hemagglutination was increased in 21.43% of the cases. In egg allergy,, the IgE was increased in 56.83% of the cases and the hemagglutination in 87.09% of all of the 31 cases studied. In the cases of milk allergy the IgE presented increases in 32% of the cases and the hemagglutination gave higher titers in 56% of all of the 25 cases studied. The results make evident that the hemagglutination should be included in the rutinary diagnosis of allergic diseases as well as the determination of total IgE or antigen specific IgE.


Effect of digitalis on skeletal muscle in man. Although an inotropic effect of digitalis on skeletal muscle has been demonstrated in animals, it has not been shown in man. Digitalis, in previous studies, has failed to improve voluntary exercise performance. In this investigation the strength of nerve-stimulated involuntary thumb adduction was measured before, during and after infusion of ouabain into the brachial artery. With this experimental design, the many uncontrolled factors that govern ordinary exercise tolerance were avoided. Large doses of ouabain (0.5 mg) produced significant augmentation of peak strength of thumb adduction whereas smaller doses (75 mug) more likely to reach the thumb during systemic digitalization produced only suggestive increases in peak contraction strength. In patients previously digitalized for heart failure, the large doses of ouabain did not significantly change contractility. The findings suggest that skeletal muscle is less sensitive than cardiac muscle to ouabain, and that systemic digitalization has a minor effect on skeletal muscle. When the differences between skeletal and cardiac muscle in excitation-contraction coupling are considered, the reduced effect of ouabain on skeletal muscle contraction is compatible with cell membrane locus of action in both tissues.


Electrophysiologic effects of procainamide in subtherapeutic to therapeutic doses on human atrioventricular conduction system. The effects of single intravenous infusions of 50 to 400 mg of procainamide on the functional properties of the atrioventricular (A-V) conduction system were studied in 36 patients and correlated with plasma concentrations. A 50 mg dose of procainamide resulted in a plasma concentration of less than 1.0 mug/ml and produced no electrophysiologic changes. Doses of 100, 200, 300 and 400 mg resulted in progresively increasing plasma concentrations (1.2, 1.8, 3.5 and 4.2 mug/ml, respectively). The effects of procainamide on the sinus rate were variable and not dose-related. The effects of doses of up to 300 mg on A-V nodal conduction were variable and not dose-related. Only in a dose of 400 mg did procainamide prolong A-V nodal conduction in six of seven patients. Whereas 100 mg had no effect on His-Purkinje system conduction, doses of 200, 300 and 400 mg prolonged His-Purkinje system conduction time by 6, 8 and 9 msec, respectively. Dose-related increases in atrial refractoriness started with a dose of 200 mg and became statistically significant with doses of 300 and 400 mg. The effects of procainamide on A-V nodal functional refractoriness were variable and not dose-related, but in doses of 100 to 400 mg, procainamide produced significant and progressively dose-related increases in His-Purkinje system refractoriness. Suppression of some types of ventricular arrhythmia by small doses of this drug may be explained by changes in refractoriness of the His-Purkinje system produced by doses of procainamide as small as 100 mg.


Intraatrial conduction disturbances: vectorcardiographic patterns. Frank P loop vectorcardiograms were recorded in 30 normal subjects and in 40 patients who had intraatrial conduction disturbances alone or in association with cardiac disease. High magnification of the P loop (0.1 mv = 3 cm) permitted accurate measurement of the P loop duration, magnitude and direction. High-frequency recordings allowed optimal evaluation of the notches, bites and conduction delays in the PsE loop. Four vectorcardiographic patterns have been selected as counterparts of the four types of enlarged P waves seen in electrocardiograms of patients with atrial conduction disturbances. When intraatrial conduction disturbances coexisted with left atrial enlargment, the PsE loop was larger and smoother. The role of partial or complete block in the specific internodal or interatrial pathways is discussed. High magnification, high-frequency vectorcardiography of the P loop seems to be the best available method for determing a specific pattern of intraatrial conduction disturbance.