Patient and bystander response to medical emergencies.

This study of patient and bystander responses to medical emergencies revealed serious shortcomings in the public's ability to respond appropriately to such situations. Decision delays at least as long as ambulance response delays were found to be the result of confusion regarding the seriousness of the emergency, confusion regarding the appropriate reaction to the emergency, and a reluctance to burden the rescue service unnecessarily. A significant group of high-risk patients were identified who not only reacted slowly but who bypassed the emergency ambulance service entirely. A substantial fraction of these patients have had prior contact with the local medical care system for problems related or identical to the one causing the emergency.


Evaluation of a cardiopulmonary resuscitation course for secondary schools.

The objective of this study was to test the feasibility of teaching secondary school students to perform cardiopulmonary resuscitation (CPR) according to National Research Council (NRC)--American Heart Association (AHA) standards. Criterion levels specified by AHA call for cardiac compression at a rate of 60 times a minute with two ventilations interposed after 15 cardiac compressions. Translated into numerical performance per minute, this standard equates to 36 compressions and six ventilations per minute. Students were instructed by their usual teachers who received a special educational program in preparation. Both immediate learning and retention of the students after three months were evaluated using a practical and a written test. Teacher performance was evaluated by means of a practical test and a behavior rating. CPR is a motor task involving both continuous and discrete processes. Results of the study corresponded to analogous studies in the psychomotor literature: practice group students' retention of continuous skills (breaths and compressions) was good (little loss of skill), while retention of discrete motor skills (open the airway, check vital signs) was poor. Fifty-five per cent of the practice group in the initial test and 31 per cent in the retention study were able to perform the skills. Retention figures compare favorably with studies in the area of psychomotor learning. The study suggests that it is possible to train secondary school students to perform the ABC's of CPR if they have an opportunity to practice these skills. The study also suggests that the teacher training is an important factor.


Primary care in a penal institution. A study of health care problems encountered.

The kinds of health care problems encountered in a 600-man panel institution were studied. Five hundred twenty-eight problems were identified in 333 inmates seen on sick call. The large number of psychosocial problems (194 out of 528) and the wide diversity of problems (125 in 333 inmates) were documented. The questionable suitability of the medical model for health care in this type of setting is discussed. The implications for primary health care delivery and education are considered.


Factors related to the preference for a female gynecologist.

Four hundred and nine female patients of both male and female physicians completed a self-administered questionnaire exploring their attitudes and practices regarding gynecologists and gynecological examinations. Responses to the question "Would you prefer a woman gynecologist?" divided the sample into three groups: those responding "yes" (33.9 percent); those responding "no" (19.3 percent); and those responding "no difference" (36.2 percent). Results revealed that patients who preferred female gynecologists were most likely to find gynecological examinations difficult and to be critical of gynecololgists' understanding of women's psychological and sexual problems. A subsample of patients in psychotherapy was especially apt to prefer female gynecologists. The "no difference" group had the most positive attitudes towards gynecological examinations and gynecologists. Demographic differences were insignificant. The importance of judging a gynecologist's competence without sexual bias, of re-evaluating stereotypes of women physicians, and of increasing the proportion of women in gynecology is stressed.


Carcinoma of the subglottic area.

The subglottic area is defined as an anatomic region which is cylindrical in shape whose inferior margin is the inferior border of the cricoid cartilage and which is limited superiorly by an imaginary circle 5 mm below the free margin of the true vocal cords. Of 591 patients with glottic and subglottic cancers, only five (percent) had primary subglottic tumors and 132 (22 percent) had glottic tumors with subglottic extension. Sixty-five percent of the patients with glottic primary with subglottic extension were Stage 2 and 35 percent were Stage 3. Most patients were treated surgically. Hemilaryngectomy is a very satisfactory primary modality in the treatment of Stage 2 and some Stage 3 glottic lesions with subglottic extension. Stage 2 and 3 glottic cancers which involve greater than 10 mm of the subglottis carry a significantly decreased prognosis. Patients with T3 lesions with cord fixation with subglottic extension show a decreased survival.


The evaluation of treatment of patients with extensive squamous cancer of the vocal cords.

Fifty-one patients with previously untreated squamous carcinoma originating on the true vocal cord, staged T4, were analyzed. Forty-eight of the 51 patients were selected for treatment. Total laryngectomy was the minimal surgical procedure, and the pathologist confirmed the presence of cancer outside the confines of the larynx in 47 of 48 patients. Seventy-three percent of the patients were thought clinically to have negative nodes, but examination by the pathologist showed a 20 percent false negative rate in this evaluation. Twenty-one percent of the patients had received an emergency tracheostomy prior to being referred to out institution. An additional 8 percent required an emergency tracheostomy or laryngectomy. Radiation therapy was employed postoperatively for 16 patients. Twenty-six (54 percent) of the 48 patients had no further evidence of cancer after treatment. In evaluating the failures, previous tracheostomy, extension of the disease to the pharyngeal wall, and positive cervical lymph nodes were found to effect adversely the survival of the patient; however, extension of the disease into the trachea, when it occurred alone, was not an adverse factor. In this patient group with a median age of 66 years, 27 percent died of causes other than the cancer within four years. Based on the data in this series, postoperative radiation therapy is now being routinely given to patients with disease extending to the pharyngeal wall, those with nodes in the neck, and those who have had an emergency tracheostomy previously.


Carcinoma of the laryngeal glottis therapy and end results.

The end results of 264 patients with vocal cord carcinoma treated by either surgery or radiation therapy at the University of Illinois from 1955 to 1972 are analyzed. Stage I glottic carcinoma can be cured by either surgery or radiation alone (86 percent and 80 percent). Stage II glottic cancer treated by surgery has achieved survival rates of 70 percent. The five-year end results of Stage III glottic cancer are 49 percent for surgery and 30 percent for radiation. The management of glottic carcinoma, according to anatomic site and indications for various modalities are discussed.


Laryngeal carcinomas.

This study is based upon 214 cases of laryngeal carcinoma treated at the Foundation Curie, Paris, France, from January, 1958, to 1968. The results in terms of five-year survival have been: (see article). A statistical study of these results was made by Professor Daudel and demonstrated the absence of significant difference for the groups of tumors classed T1 and in Stage I and II treated either by radiocobalt or by surgery, whether followed or not by radiotherapy. By contrast there was a clearly significant difference in favor of surgery for the group of tumors classified as T2, T3, T4, or in Stage III. This significant difference in favor of primary surgery disappeared if we excluded the patients who died of intercurrent illnesses or of a second cancer not involving the larynx, and when we took into account those cures obtained by surgery in the event of failure of radiation and inversely, of those cures having been obtained by radiation therapy in the event of failure of surgery.


The management of glottic carcinoma by primary irradiation with surgery in reserve.

Four hundred nineteen cases of carcinoma of the larynx (1962-1965, Christie Hospital) treated primarily by radiation with surgery in reserve for cases where radiation failed, are reviewed. Two hundred ninety-one of these cases were glottic carcinomas and cure rates, and contribution from subsequent surgery is indicated in detail. Finally the overall results are compared with a larger series of 605 cases (1955-1961). Five-year cure rate in early cases is consistent at 89 percent; likewise in the latest cases at 30 percent, the intermediate group appear to have improved by some 8 percent over the period outlined. The overall cure rate is 70 percent.


The treatment of glottic carcinoma: an analysis of 800 cases.

All patients with cancer of the glottis seen at the Ontario Cancer Institute from 1955 to 1971 are reviewed. Changes in referral patterns and treatment policy are noted. Particular attention is given to those patients who received radiation for cure, and the place of laryngectomy in their subsequent management is examined. Of the estimated incidence of the disease in the geographic region served, 95 percent are now being seen and of these 97 percent receive treatment with curative intent. Two-thirds or 67 percent are cured at five years and their larynges intact, while a further 18 percent are cured by subsequent laryngectomy.


Radiotherapeutic management of cancer of the glottis, University of Virginia, 1956-1971.

All patients with cancer of the glottis treated by radiotherapy with curative intent at the University of Virginia from 1956 through 1971 have been reviewed. Follow-up is complete through December, 1973. Results are presented by both stage and treatment policy and indicate that with our present methods of management a high degree of local control is achieved. The complications of treatment are examined, particularly those arising as a result of combined radiotherapy and surgery. A small number of cases have been salvaged following local recurrence and these are described in detail. Particularly striking has been the effectiveness of radiotherapy in the treatment of advanced (Stage III and IV) lesions. In this group 58 percent of the patients survive with their larynges intact. Considering the poor general condition and advanced nature of the lesions in these cases this result is important and may indicate the nature of future trends in treatment, namely radiotherapy, with surgery held in abeyance until there is overt recurrence.


Conservative neck dissection.

The areolar tissue which fills the laterovisceral spaces of the neck is thought to be in close contact with the limiting muscle and the large vessels and nerves of the neck. The site of lymph nodes and lymphatic vessels in such tissue is not clearly defined. A more profound anatomical study shows that the areolar tissue contains the whole lymphatic system of the neck, limited by a series of aponeuroses. These are derived from the embryonal mesenchyme, surrounding muscles and vessels, giving origin to a series of compartments which are in continuity with each other. These compartments, which contain the lymphatic structures, may be entirely removed en bloc including their limiting aponeurotical membranes, as long as the latter are carefully stripped from the muscular and vascular structures. This technique of neck dissection originating with O. Suarez in Argentina, is as radical as any traditional neck dissection, providing that some technical details are respected and that the nodes are still mobile. By preserving many useful or necessary structures of the neck, which themselves are unrelated to the lymphatic spread of cancer, conservative neck dissection presents important functional and cosmetic advantages as compared with traditional neck dissection.


Analysis of surgical therapy for epidermoid carcinoma of the laryngeal glottis.

Four hundred sixty-three patients with glottic carcinoma were treated by surgical techniques with or without preoperative irradiation. Two hundred eighty-one had hemilaryngectomy and 182 total laryngectomy procedures. The overall cure rate for the hemilaryngectomy group was 91 percent and 80 percent  for the total laryngectomy group, with an overall cure rate of 87 percent. Our observations support the fact that Stage I glottic carcinoma has slightly better prognosis when treated by hemilaryngectomy. Stage II and III lesions have a significant improvement in cure rate and survival when treated with combined preoperative irradiation and partiall vertical laryngectomy or total laryngectomy than by irradiation alone.


Evaluation of nasal tip surgery.

Nasal tip surgery has been evaluated with respect to correction of the lower lateral cartilages. Indications, techniques, results, and complications related to three generic approaches to the lower lateral cartilages are described. In 673 consecutive rhinoplasties the commonest type of nasal tip surgery was excisional, utilizing either a marginal or cartilage splitting technique. These techniques were utilized: 1. to accomplish debulking, and 2. to accomplish the installation of facets. The excisional technique found its greatest utility in primary rhinoplasties. The version technique, utilizing a change of direction of the thrust of the lower lateral cartilages was utilized in a variety of situations, particularly for the correction of moderately congenitally hypoplastic tip cartilages. It also found great utility in surgery of the Negro or cleft palate nose, increasing tip projection, correcting unacceptable bifidity, and in revision rhinoplasty. Augmentation rhinoplasty, utilizing conchal cartilage as an elastic strut was particularly useful for severe hypoplastic cartilage deficits, the Negro nose, columellar retraction, and alar rim deficits. The overall complication rate of lower lateral rhinoplasty was 17.4 percent. The rate of unacceptable complications related to lower lateral rhinoplasty was 2.7 percent.


Life-threatening complications of infectious mononucleosis.

Infectious mononucleosis is a common febrile disorder of children and young adults which is generally benign and self-limited. Patients with this disorder, however, may develop life-threatening complications which require prompt recognition and treatment. The clinical features of three such cases are presented and pertinent features of other life-threatening complications are reviewed.


Human auditory nerve responses: a comparison of three commonly used recording sites.

The computer-averaged N1 response from humans to click stimuli was compared at three recording sites -- dermal and subdermal electrodes in the ear canal, and a transtympanic electrode on the promontory. A total of 26 subjects, some of whom were measured at all three sites, participated in 47 experiments. The promontory electrodes were consistently more sensitive and yielded cleaner N1 waveforms than did the ear canal sites. In considering the clinical use of N1 averaging, the advantages of the transtympanic method outweigh the risks. While a few persons yield reasonable good ear canal potentials, the reliablitity of this method in general application is inadequate and unpredictable.


The role of the middle ear in acoustic trauma from impulses.

Exposure to high intensity impulse noise may produce a wide range of audiometric and histological effects in experimental animals. The objective of this study was to assess the changes in the middle ear mechanism after impulse noise exposure and to relate these changes to the audiometric and histological effects. Nine monaural chinchilla were exposed to either 161 or 166 db peak SPL impulses of 1 msec "A" duration, presented at a rate of 1 per minute for 50 minutes. The conductive mechanism of the chinchilla was assessed using standard clinical measures of static and dynamic impedance before and after the noise exposure. Auditory thresholds were measured before and after noise exposure using the average evoked response (AER) technique. At 30 days post-exposure, the animals were sacrificed for histology. Pre-exposure tympanometry showed that: 1. the total mean impedance of the chinchilla ear is considerably lower than that of man; 2. a method related hysterisis effect is present in both the susceptance and conductance tympanograms; and 3. sedation has a significant effect on the total impedance of the ear and on the shape of the tympanograms. After exposure to high level impulse noise: 1. tympanograms become irregular and double peaked, indicating tympanic membrane stress; 2. for the given exposure, 166 db is the impulse intensity needed to rupture consistently the tympanic membrane; and 3. audiometric and histological data correlate with the tympanometric findings and demonstrate a protective effect of a tympanic membrane rupture on the cochlea.


Brassica compestris var. Span: I. Fractionation of rapeseed oil by molecular distillation and adsorption chromatography.

Procedures for the large scale isolation of pure triglycerides and fractions rich in nontriglyceride components from Span rapeseed oil are described. Fractionation of Brassica campestris var. Span rapeseed oil by molecular distillation yielded 4 triglyceride fractions, all of which contained traces of sterol esters. An additional triglyceride fraction rich in free and esterified sterols and other volatile components was obtained from the oil. Separation by adsorption chromatography of Span rapeseed oil yielded three fractions; A) a pure triglyceride ffaction; B) a triglyceride fraction rich in sterol esters; and C) another fraction containing free sterols and other polar components.


Brassica campestris var. Span: II. Cardiopathogenicity of fractions isolated from span rapeseed oil when fed to male rats.

Rapeseed oils low in erucic acid caused myocardial lesions when fed to weanling male rats for 16 weeks. The cardiopathogenic properties appear to be associated with the triglycerides of the oil, and not to nontriglyceride components present in fully refined rapeseed oil. Cardiac lipid analysis confirmed that erucic acid accumulation was proportional to the concentration of this acid in the diet.


Reaction of ergosteryl acetate with maleic anhydride and preparation of 5,7-ergostadien-3beta-ol1,2.

An improved, large scale synthesis of the ergosteryl acetate-maleic anhydride Diels-Alder adduct and its pyrolysis are described. The complex mixture obtained by reaction of the two constituents was refluxed with methanol to convert the succinic anhydride derivatives, formed by the "ene" reaction, to soluble half esters, leaving the insoluble Diels-Alder adduct largely unchanged. The latter was hydrogenated and pyrolyzed in vacuo to yield 5,7-ergostadienyl acetate together with lesser quantities of the acetates of 7,9(11)-ergostadien-3beta-ol, 6,8(9)-ergostadien-3beta-ol, and 8,14-ergostadien-3beta-ol. These components were separated and purified by argentation column chromatography and crystallization.


Unique pathways of sterol metabolism in the Mexican bean beetle, a plant-feeding insect.

Radiolabeled sterols, 14C-cholesterol, 14C-cholestanol, 3H-stigmasterol, 3H-stigmastanol, and 3H-sitosterol, were fed to larvae of the Mexican bean beetle, Epilachna varivestis Mulsant, bu coating soybean leaves. Free sterol and sterol ester fractions from treated insects were isolated and analyzed, and in each case nearly 30% or more of total radiolabeled sterols retained by the insect were found in the sterol ester fraction after 8 days. delta5-Dietary sterols were readily reduced to stanols, and C29-stanols thus produced were dealkylated to cholestanol. Significant amounts of labeled lathosterol were formed from delta5-C29 sterols; little, if any, radiolabeled cholesterol was detected in insects fed either of the labeled delta5-phytosterols, stigmasterol or sitosterol. Sterol metabolism of this insect thus differs considerably from that found for most phytophagous insects.


Elongation and desaturation of dietary fatty acids in turbot Scophtalmus maximus L., and rainbow trout, Salmo gairdnerii rich.

Turbot and rainbow trout, which had previously recieved diets free of fat, were fed [1-14C] fatty acids. The distribution of radioactivity in the tissue fatty acids was examined 6 days later. In rainbow trout fed [1-14C] 18:3omega3, 70% of the radioactivity was present in 22:6omega3 fatty acid. In contrast, turbot fed [1-14C] 18:1omega9, 18:2omega6, or 18:3omega3 converted only small amounts of labeled fatty acids (3-15%) into fatty acids of longer chain length. The major product of the limited modification found in turbot was the dietary acid elongated by 2 carbon atoms.


Methylating activity of (methyl-14C)-S-adenosylmethionine by microsomes of the insect Ceratitis capitata.

The methylating activity of (methyl-14C)-S-adenosylmethionine by microsomes from different stages of development of the insect Ceratitis capitata was studied in a series of in vitro experiments. Larval and pharate adult microsomal preparations were used in the in vitro conditions, and the utilization of the methyl group of the S-adenosylmethionine for the synthesis of phospholipids was evaluated. Incorporation of radioactivity in lipids by pharate adult microsomes was significantly higher than that by larval preparations. In both cases, phosphatidyl ethanolamine showed the highest levels of radioactivity incorporation. Free bases from total lipid hydrolysates were resolved by paper chromatography, and the labeling was investigated by radioactivity scanning of paper chromatograms. Larval and pharate adult preparations showed clearly the presence of dimethylethanolamine and choline. The presence in the incubation media of phosphatidyldimethylethanolamine and deoxycholate enhanced the radioactivity incorporation into choline, whereas, the first stages of methylation were inhibited. These findings confirmed previous results using insect homogenates.


Enzymatic synthesis of glucocerebroside by UDP-glucose: ceramide glucosyltransferase during ontogenesis of chicken retina.

The activity of uridine diphosphate-glucose: ceramide glucosyltransferase during chick retina ontogenesis was studied. This enzyme catalyzes the first step in the biosynthetic pathway leading to gangliosides. The glucosyltransferase activity was detected in 8 day old embryos, and was present in adult animals. The highest specific activity was found ca. day 10 of embryonic life. The radioactive product was identified as glucocerebroside by means of radiochromatography. The presence of phosphatidylcholine in the incubation mixtures was found to stimulate the enzyme.


Analyses of renal medullary lipid droplets from normal, hydronephrotic, and indomethacin treated rabbits.

Lipid droplets isolated from rabbit renal medullary tissue were analyzed and found to be composed of triglyceride and free fatty acids in a ratio of 2.9:1. These triglycerides were unique when compared to triglycerides of other rabbit tissues examined, in that they contained high percentages of octadecanoic acid (stearic acid, 9.8%), 5,8,11,14-eicosatetraenoic acid (arachidonic acid, 6.8%), and 7,10,13,16-docosatetraenoic acid (adrenic acid, 10%). Lipid droplet triglycerides were found to increase during experimental hydronephrosis and after administration of indomethacin, a prostaglandin synthetase and phosphodiesterase inhibitor. From gas liquid chromatography of fatty acid methyl esters of these triglycerides, it was determined that they were enriched further in their percent composition of 9,12-octadecadienoic acid (linoleic acid) and arachidonic acid, a prostaglandin precursor. The inverse relationship between lipid droplets and prostaglandin content in the inner medulla suggested a significant role of lipid droplet triglycerides as storage pools for prostaglandin precursors.


High levels of pancreatic nonspecific lipase in rattlesnake and leopard shark.

Hydrolysis of synthetic triglycerides by rattlesnake and leopard shark pancreatic enzymes revealed striking differences in specificity, depending on the presence or absence of sodium taurocholate. Without added sodium taurocholate the classical specificity of pancreatic lipase was expressed. Rattlesnake enzymes, in the presence of sodium taurocholate, attacked the unsaturated oleic acid in the 2-position of racemic glycerol-1-palmitate-2-oleate-3-stearate nearly twice as fast as either outside saturated fatty acid. In this instance, over 90% of the monoglyceride which accumulated were 1-monoglyceride. These results are attributed to very high levels of bile salt activated nonspecific lipase. Eight vertebrate species were compared. With the exception of the rattlesnake and leopard shark, the other species (3 elasmobranchs and 3 mammals) all exhibited low levels of nonspecific lipase, e.g. less than 5% hydrolysis of the 2-position of racemic glycerol-1-palmitate-2-oleate-3-stearate in the presence of sodium taurocholate.


Bile acid metabolism in mammals: IX. Conversion of chenodeoxycholic acid to cholic acid by isolated perfused rat liver.

Current dogma of bile acid synthesis in mammals insists that hydroxylation of the ring structure at C-12 precedes side chain oxidation, and that chenodeoxycholic acid is not converted to cholic acid under normal conditions. This report concerns the conversion of chenodeoxycholic acid to cholic acid by isolated, perfused rat liver. Results indicate that isolated perfused rat liver has a definite, but limited, capacity for synthesis of cholic acid from chenodeoxycholic acid.


[Respiration of an obligate methylotroph in the presence of various substrates].

Respiration of the cells of Methylococcus ucrainicus, strain 21, cultivated in the atmosphere of methane, is stimulated by methanol, formaldehyde, formate, n-alcohols, and allyl alcohol. The rate of oxygen assimilation is lower in the presence of isopropanol, isobutanol, propane, butane, maltose, and some organic acids (acetate, fumarate, citrate, succinate). The Michaelis constant for methanol is 88 mcM. Oxidation of methane, methanol, formaldehyde, and formate by the bacterium is inhibited by cyanide, hydroxylamine, and azide. The rate of oxygen assimilation by the cells in the presence of methane and other C1-compounds did not decrease after the suspension had been stored at 4 degrees C during four months and longer.


[Makeup of free intracellular amino acids in Cunninghamella elegans growing on media with hydrocarbons].

The rate of growth of Cunninghamella elegans (--) 1204 is higher on a mineral medium with glucose (6.56 g/litre) than on a mineral medium containing undecane, tridecane, and pentadecane (0.72--0.87 g/litre); all glutamic acid is consumed only from the medium with glucose. The cells contain 15--16 free amino acids and 1--2 amides, glutamic and aspartic acids and alanine prevailing. The culture grown on the medium with glucose contains asparagine, and the cells cultivated on the medium with alkanes contain histidine. Non-proteinogenous aminobutyric acids were found in the pool of the cells grown on all tested media with an exception of the medium containing undecane.


[Fatty acid makeup of the lipids in soil and epiphytic yeasts].

The fatty acid composition of lipids was compared among yeast cultures belonging to the genera Rhodotorula, Lipomyces, and Cryptococcus. These lipids contain C10--C26 fatty acids, mainly with the even number of carbon atoms. Palmitic acid (C16 : 0) and oleic acid (C18 : 0) predominate. In the majority of the strains, the sum of unsaturated acids exceeds the sum of saturated acids. The content of unsaturated acids in the lipids of the epiphytic yeast Rhodotorula is higher than in the soil yeast Lipomyces. Besides C12--C18 acids, C22--C26 acids were identified by GLC at preset temperatures. Lignoceric acid (C24 : 0) was found for the first time in the cultures of Rhodotorula, Lipomyces, and Cryptococcus, and cerotinic acid (C16 : 0) was also detected in the Rhodotorula yeast. Fatty acids with a long chain are registered in the strains of Rhodotorula more often than in the strains of Lipomyces and Cryptococcus.


[Growth of Thiocapsa roseopersicina purple sulfur bacteria in darkness under anaerobic conditions].

The phototrophic sulphur bacterium. Thiocapsa roseopersicina, strain BBS, was grown under anaerobic conditions in the darkness on the medium containing glucose and thiosulphate or molecular sulphur. The assimilation of glucose is accompanied by the accumulation of small amounts of pyruvate in the medium, and the uptake of thiosulphate or molecular sulphur leads to the formation of sulphates and hydrogen sulphide.


[Thermus ruber obligate thermophilic bacteria in the thermal springs of Kamchatka].

The new species of the obligate-thermophilic bacterium Thermus ruber is widely distributed in hot springs of Kamchatka with the temperature of water from 57 to 90 degrees C. The bacterium does not oxidize sulphur. It contains a red carotenoid pigment similar to neuro-sporaxanthine and retrodehydro-gamma-carotene.


Society and the doctor.

With the changing times, concepts of morals and values of life are changing too. The responsibility and role of the doctor is taking on a new shape in his decision-making for the care of the sick members of his society. The pattern of diseases is changing, as is the doctor's relationship to his clients. It is necessary for society to share responsibility for several social diseases, perhaps under his expert guidance. Finally, it is vital for society to provide him with a milieu in which he can work efficiently and effectively.


[Isolation and characteristics of the cellular structures of Candida tropicalis].

Using the method of radioactive indicators, the specific content of proteins, lipids, total phosphorus, and lipid phosphorus was estimated in the morphological cell fractions of Candida tropicalis after growth in a liquid mineral medium containing n-octadecane as a source of carbon. The morphological cell fractions were produced by means of differential centrifuging. The following comparatively pure fractions were obtained simultaneously: soluble fraction, microsomes, mitochondria, large membranes, and cell walls.


[Arthrobacter siderocapsulatus isolated from lake water].

Two microbial strains have been isolated from lake water. The strains oxidize ferrous compounds and manganese. By the structure of microcolonies and the character of deposited oxides of these metals, the strains are identical to the genus Siderocapsa. However, according to their growth cycle and some morpho-physiological characteristics, they were included into the genus Arthrobacter (Corynebacteriaceae). Since these microorganisms differ, by their cultural and morpho-physiological properties, from other species of this genus, they were classed as a new species. Arthrobacter siderocapsulatus nov. sp.


[Distribution of hydrocarbon and wax in the cells of Mycobacterium ceroformans].

The distribution of hydrocarbon and wax was studied in the cells of Mycobacterium ceroformans. The cells were disintegrated in French press and the content of hydrocarbon and wax was determined in the cell-free extracts. Hydrocarbon and wax are accumulated in the cell walls of Mycobacterium ceroformans.


[Distribution of Rhodosporidium diobovatum yeasts in soil and on plants].

As was found by the hybridization technique, 43 strains among 92 studied strains of the yeast Rhodotorula glutinis belong to Rhodosporidium diobovatum Newell et Hunter (Ustilaginaceae, Basidiomycetes). The strains of Rhodosporidium diobovatum were found in oil-bearing soils, rhizosphere, and phyllosphere of cultivated and wild plants.


[Spectral characteristics of Micropolyspora spp. and of actinomycetes similar to them].

IR spectra of the whole cells of oligosporous actinomycetes were studied. These spectra can be used as an additional criterion during identification of actinomycetes at the generic level, and confirm the heterogeneity of the Micropolyspora genus so that some of its species may be classed as an individual genus (Kalakoutskii et al., 1968; Agre, Dorokhova, 1972).


[Electrocardiographic and phonocardiographic findings in Ebstein's anomaly with special regard to its severity (author's transl)].

Electrocardiographically, the combination of the P-dextro-atriale and the RBBB without right ventricular overload almost certainly constitutes a pathognomonic finding in Ebstein's anomaly. The height of the P wave and the duration of the QRS complex are related the the severity of the anomaly. So the higher the P wave, the wider the QRS complex, the more severe is the Ebstein'ngs are detectable in the phonocardiogram. In the mild form, however, a loud systolic click and occasionally a low systolic murmur are present, while in severe forms, there is only a loud systolic murmur, and no systolic click.


[Efficacy of a new slow-release isosorbide dinitrate preparation in myocardial infarction (author's transl)].

A new slow-release isosorbide dinitrate preparation (ISDN retard, Boehringer Mannheim) was investigated in a controlled study (double blind/cross over) in 20 patients with clear symptoms of coronary insufficiency after myocardial infarction, comparing the ECG on effort with that under placebo treatment. A favourable effect on the symptoms of coronary insufficiency could be demonstrated under standardised conditions on a bicylce ergometer 4 hours after oral ingestion of ISDN. The ST interval of the ECG was significantly lowered (p less than or equal to 0.025) under comparable cardiac work. The prolonged action of ISDN retard was also shown by a significant reduction in systolic and diastolic blood pressure at rest, during and after effort. Simultaneously, there was a slight but not-significant rise in heart rate.


[Development of Thermoactinomyces vulgaris on a synthetic medium].

A synthetic medium was used to obtain the dormant spores of Thermoactinomyces vulgaris. The fraction of the dormant spores depended on the amino acid composition of the growth medium. The rate of growth and development of the organism on the synthetic medium is lower as compared to the routinely employed complex medium.


[Enteral absoprtion of ascorbic acid in man after application of a micro-encapsulated retard preparation (author's transl)].

Blood level determinations of ascorbic acid were carried out in 11 male probands after oral application of a new vitamin C retard preparation. In comparative tests the same probands received identical doses of a non retarded vitamine C preparations after a period without application of 2 weeks. The results obtained show that after application of the new vitamin C retard preparation the absorption of ascorbic acid is increased and thus a marked improvement of the bioavailability of vitamin C is attained as compared to the non retarded form.


[Isosorbide dinitrate in coronary heart disease. Effects of a delayed-action preparation during acute load and in chronic use].

The antianginal effectivity of a sustained release isosorbiddinitrate Sorbidilat Retard drug was examined by the number of spontaneous attacks and by ergometry with a constant work load in a double blind trial with cross over technique. An effect on the stress duration, on the ST segment depression, on the "double product", on heart rate, and blood pressure could be proved, which is interpreted as an therapeutic advantage of serum against placebo. The number of spontaneous attacks could be reduced in the verum period significantly. Ergometry every 2 hour after drug adminstration shows an oral effectivity of about 10 hours.


[Pacemaker failure due to electromagnetic interference (author's transl)].

Pacemakers may be influenced by a variety of external methods such as a magnet to test the stimulation threshold or a special programmer to change the pacers output or rate. This designed influence must not be confused with electromagnetic interference on pacemakers. The paper differenciates between functional and faulty behavior of pacemakers. A case report shows the influence of EMI by electrical devices. It is recommended to undertake field tests if EMI is likely to occur under special occupational conditions.


[Late diagnosis of thrombosis of the pelvic, femoral or calf veins (author's transl)].

The time interval which elapses from the occurrence to the diagnosis of thrombosis of the pelvic, femoral or calf veins was investigated in a retrospective study. As could be shown from the histories of 66 patients with phlebographically documented localization and extent of the thrombosis, in 85% of the cases the correct diagnosis was only made past the 7th day following the presumptive beginning of the thrombotic process, i.e. at a time when the period optimal for a fibrinolytic or surgical treatment had already passed. J-fibronogen-method in patients with an increased risk for thrombotic complications is recommended.


[Androgen status of male diabetics. Total testosterone before and following stimulation with HCG, free testosterone, and testosterone binding capacity of patients with and without potency disorders].

In order to investigate the androgen status of diabetics we determined in 39 patients, 18-60 years old, 17 of which suffered from potency disturbances, the basal total plasma testosterone, the free testosterone fraction and the unbound plasma testosterone as well as the testosterone binding capacity. In 39 of these patients we proved the response of Leydig cells to HCG. Between normal persons and patients with and without potency disturbances basal total plasma testosterone did not differ significantly (p greater than 0.10). After a 3-day stimulation with HCG the increase of basal total plasma testosterone was significantly lower in the two diabetic groups in comparison with the normal persons (p less than 0.0005). The group with potency disturbances had significantly lower values for the free testosterone fraction (p less than 0.005) and unbound plasma testosterone (p less than 0.0025) than normal persons whereas diabetics without potency disturbances did not reveal any significant differences (p greater than 0.25 and p greater than 0.40). Further there were significant differences between the patients with and without potency disturbances (p less than 0.025) and (p less than 0.025). Testosterone binding capacity was significantly increased in the group with potency disturbances (p less than 0.0005) and also in the group without potency disturbances (p less than 0.01) as compared with controls. Moreover was it significantly higher in the group with potency disturbances than that without potency disturbances (p less than 0.01). For none of the parameters a functional correlation of age or diabetes duration could be demonstrated. The results are discussed with regard to the causes of potency disturbances in male diabetics.


[Gastrointestinal complications of diabetes mellitus].

The gastrointestinal complications of diabetes mellitus are the outward forms of the diabetic visceral neuropathy. The diabetic damage of the vagus nerve leads to disturbances of the tonus and the motility resembling to postvagotomy like conditions in the following clinical forms: diabetic dysphagia, diabetic gastroparesis, diabetic diarrhoea, diabetic megacolon, diabetic cholecystomegaly. These are in general late complications of labile diabetes. The mild abdominal symptoms are not in proportion to the severe radiological changes, proper diagnosis may be obtained only by means of roentgenological examinations in most cases.


Evidence for a dual control of the initiation of host-cell lysis caused by phage lambda.

The timing of host-cell lysis by coliphage lambda is controlled by two separable systems. The lambdaS gene product acts as a positive effector of lysis while another protein, the lysis regulator, is an inhibitor of lysis. If the continuous function of the lysis regulator is interrupted in phage infected cells immediate lysis ensues. This lysis requires metabolic energy but not S gene activity. In contrast, S protein activity is stimulated by agents which uncouple and which block oxidative phosphorylation. The lysis regulator is thermolabile and several lines of evidence suggest that it may be the lambdarex gene product.


RNA polymerase binding sites isolated from T4DNA: analysis of oligopyrimidine sequences constituting preinitiation and initiation complexes.

Oligopyrimidines which contain 5'-hydroxymethylcytosine instead of cytosine were separated by thin layer chromatography. Using this method, the oligopyrimidine pattern of RNA polymerase binding sites, isolated from T4DNA, was evaluated quantitatively. The analysis shows that 1. the RNA polymerase binding sites on T4 DNA obtained under low salt conditions in absence of triphosphates, are A-T-rich as compared with total T4 DNA. 2. The A-T base pairs stand mainly in alternating position. On the average these sequences comprise more than half of the chain length of each binding site, which contains about 8 G-5'-HMC pairs. 3. The sites of binding and the sites of initiation do not show an identical base composition. 4. A mixture of at least 8 different binding istes is isolated under the conditions employed. This figure is in agreement with the number of distinct transcripts synthesized in nitro by E. coli RNA polymerase from T4 DNA. The overall length of these transcripts corresponds to approximately 9% of the T4 genome.


The synthetase gene of the RNA phages R17, MS2 and f2 has a single UAG terminator codon.

Translation of the RNA from the wild-type bacteriophages R17, MS2, and f2 in bacterial cell-free extracts containing an amber suppressor yields 30-40% of the synthetase with an approximate molecular weight of 63 500, slightly larger than the major synthetase product (63 000 daltons). The occurrence of the 63 500 dalton in vitro product is dependent on the presence of an amber suppressor, and we predict that it is due to read-through of a UAG termination codon at the end of the synthetase gene. Previous results of Capecchi and Klein (Nature, 226, 1029-1033, 1070) showed that antibodies to both release factors RF1 and RF2 are required to block release of synthetase, suggesting that synthetase is released at a UAA codon. If the interpretations of both experiments are correct, the termination and release may not be synonomous and may be spatially separated. In addition there is the unexplained fact that 7% of the synthetase made in vitro in both su+ and su- extracts with either R17, MS2 or f2 as template has an apparent molecular weight of 66 000.


Ultraviolet reactivation of the single stranded DNA phage phiX 174.

When UV-irradiated phiX174 was grown in pre-irradiated host cells of various strains, "ultraviolet reactivation" (UVR) was observed only in recombination proficient strains such as E. coli C (uvrA+ recA+) and HF4704 (uvrA- recA+), but not in the recombination deficient strain HF4712 (uvrA+ recA-). By increasing the multiplicity of infection, no rise in the amount of such reactivation was observed. From the study of the neutral and alkaline sucrose gradient sedimentation patterns of DNA samples extracted from unirradiated cells infected with unirradiated phage, it appears that after the conversion of the viral single stranded (SS) DNA to the double stranded form (DS), "nicks" or scissions were produced on it within all three strains, which were ultimately sealed up in the recA+ but persisted within the recA- host cells. When UV-irradiated phage infected unirradiated host cells, such nicking of the DS DNA appeared to be much more extensive in uvrA+ recA+, but slightly reduced in uvrA+ recA- and severely suppressed in uvrA- recA+ strains. When the host cells were also UV-irradiated, the conversion of the infecting viral SS DNA to DS DNA as well as its subsequent nicking were reduced in all the three strains to a much greater extent. Although nicking of the DS DNA molecule is an essential step even in the normal intracellular replication of phiX DNA, the production and the sealing up of such nicks appear not to have any positive correlation with UVR of these phages. A drastic reduction in nicking due to pre-irradiation of the host cells might, however, mean slowing down of the replication of the damaged parental RF molecules which would facilitate their repair perhaps through recombination with the homologous parts of the host genome.


Insoluble collagen of methylcholanthrene induced sarcoma.

The insoluble collagen from methylcholanthrene induced sarcoma was isolated and characterized. It contains more glycine, hydroxyproline and acidic amino acids than normal connective tissue collagen. An anionic character of tumour collagen was stated (pI 6.1). No typical collagen subunits in this protein were found. The tumour collagen is strongly bound to acidic glycoprotein containing a significant amount of hydroxylysine. Such an insoluble complex is resistant to the dispersing action of EDTA. It dissociates during heating in concentrated urea.


The normal orbital phlebogram. A study of the normal variations.

Using a modified phlebographic technique, the author has gained a better and more constant filling of the smaller intraorbital veins than earlier reported. 57 normal orbital phlebograms have been used to evaluate the normal phelbographic anatomy of the orbit. A preliminary presentation of the findings is given.


Differential diagnosis of orbital tumors by echography A. A clinicopathological study of 54 cases.

In 54 cases of unilateral, surgically verified, exophthalmus usefulness of echography A was compared with histopathological diagnosis. Presence of abnormal tissue was detected in almost all of the cases. Comparison between the echograms and the pathological examination clearly demonstrates that a precise diagnosis is not yet possible with ultrasonography. Different tumors may give identical echograms and conversely histologically similar tumors may produce different types of tracings.


Unilateral exophthalmos investigated by infrared thermography.

A group of 40 cases of unilateral exophthalmos have been investigated using infrared thermography. Two groups of cases can be distinguished according to the intensity of thermal anomalies: (a) no hyperthermy, allowing exclusion of an acute inflammation and rather suggesting an endocrinal process that nevertheless includes the possibility of a deep and/or weakly thermogenous tumor and (b) marked orbital hyperthermy, excluding any endocrinal origin and generally reflecting a malignant tumor.


Therapy of blow-out fractures.

The number of patients with fractures of the bony orbit has recently increased because of increasing accidents, expecially car accidents. Due to the good cooperation of maxillofacial surgeons and ophthalmoligists the latter are asked for consultation in the first days after the accident. Therefore the possibility exists to diagnose rather often a blow-out fracture even without X-ray examination. The methods of primary and secondary management are enumerated.


Long-term follow-up of orbital blow-out fractures with and without surgery.

The patients having orbital repair for a blow-out fracture, 6 months or longer after injury, had a high incidence of enophthalmos (72%). This compares badly with 17% in the non-surgical group and 20% of those who had surgery within 14 days of trauma. The residual enophthalmos was minimal in the latter two groups, but could measure 2 or 3 mm in the late surgery group. 40% of the late surgery group also needed additional orbital or muscle surgery and the fields of binocular single vision achieved were only moderately good. The good results achieved without surgery do not, of course, mean that patients with blow-out fractures do equally well regardless of surgical treatment. This study has shown that careful clinical and radiological assessment in the first 10 days permits a reasoned decision to be made whether to operate or not on any particular patient.


Reconstruction of the orbital roof by acrylic prosthesis.

Presentation of two cases of open orbital roof fracture with destruction of all the orbital roof extending from the fronto-maxillo region to the spina orbitalis. After a first emergency neurosurgical treatment, a cast of the excised soiled bone fragment was taken and identical replica was made from methylmethacrylate. In a second surgical procedure, the resine mould was set in place by endocranicl approach, and was fastened firmly to the surrounding bone with wire sutures. In such types of defects cranioplasty and orbitoplasty are mandatory.


Orbital roof fractures.

This paper is based on experience with 28 orbital roof fractures in 23 patients treated over a period of 2 years. The symptomatology and treatment of the rim, the linear and the comminuted orbital roof fractures are given. Our conclusion is that with adequate treatment, the permanent sequelae can be limited.


Fractures of the middle third of the face.

Middle third fractures have increased in number over the past two decades. Since different disciplines take an interest in their management different names are often given to identical fractures. We classify the fracture types, and their treatment is briefly discussed. Results of treatment of about 500 patients with middle third facial fractures are presented. Part of the fracture involved one or both orbits. A comparison with recent literature was made. Early diagnosis and treatment is essential. Insertion of an implant on the orbital floor through an infraorbital incision can be omitted in fresh fractures. This procedure is rarely indicated except in some old untreated fractures.


Clinical, surgical and pathological considerations on a series of 74 operated tumours of the orbit.

A survey is given of 74 orbital tumours that were operated during the past 10 years and that gave indications to operate (exophthalmia, tenderness, diplopia, loss of vision). The value of the modern clinical investigation like arteriography, pneumotomography, phlebography, echography and scintigraphy is discussed. The location of the tumour is the deciding factor whether to choose the neurosurgical approach, orbitotomy, or even exenteration. The high proportion (14%) of inflammatory pseudo-tumours in the orbit is remarkable.


Orbital corrections with the use of alloplastic material.

After a severe trauma of the face, e.g. fractures involving the zygoma, the upper jaw or other orbital bone alteraions and deviations of the bony orbital contours and also of the orbital contents can subsist, even after primary operative correction. The patients have functional as well as cosmetic complaints. In consequence of eyeball dislocation and incarceration or fibrosis of the external eye muscles, the patients also complain of diplopia in one or more directions. Due to the bony orbit enlargement and reduction of the orbtial contents, the eye is moved inferiorly and backwards, also causing diplopia, ptosis and a deep sulcus of the upper lid. The treatment consists in closing and sufficient raising of the orbital floor correction of the enophthalmos. To cover the floor fracture, we apply 1-8 perforated Teflon implants which are placed under the periost of the orbital floor. To correct the enophthalmos, we use 30-50 Teflon beads with a diameter of 5 mm, and placed them in a sub-periorbital pocket laterally above and behind the eyeball, thus ensuring that the eye will be forced forwards in the cone-shaped orbit and so diminish or eliminate the enophthalmos. The operation is performed in close cooperation between an ophthalmologist and a plastic surgeon. Most of our cases also needed operative muscle correction. Although not all deviations could be totally corrected, we always achieved a clear improvement, and all 36 patients obtained a useful field of binocular single view. Until now we have had no implant infections or rejections. We should like to consider that this method of correction will have its own place in the treatment of orbital deformities.


Orbital venography of Kasabach-Merritt syndrome.

A case of hemangioma involving the orbit and jaw associated with thrombocytopenia in a 1-month-old boy was reported. To our knowledge, this combination of two hemangiomas has never been reported. By utilizing venography we could diagnose the mass as being a hemangioma. Radiotherapy was successful giving 500 rad to the mass on the right jaw. At follow-up after 2 months, the platelet count had returned to the normal range and the hemangiomas were noted to have regressed dramatically.


A genetic study of plasma dopamine beta-hydroxylase in affective disorder.

Plasma DBH activity was studied in patients with affective illness (unipolar or bipolar) and in their families. We found diagnosis, mood state or lithium treatment did not modify plasma DBH activity. In family studies we found same-sex siblings to show significant correlations for plasma DBH activity regardless of diagnosis. Monozygotic twins had almost identical DBH activities; 4 pairs of monozygotic twins discordant for affective illness were concordant for DHB activity. The heritability estimate for plasma DBH activity is greater than 0.90, indicating a strong genetic influence. These studies reveal that affective illness does not modify plasma DBH activity and that familial factors play an important role in controlling plasma DBH activity.


[In vitro tests as a tool for examination of the thyroid function in childhood and newborn stage (author's transl)].

The concentration of hormone iodine, total thyroxine and the T3-test were determined in children from the newborn-period until school-age. Hormone iodine and total thyroxine increased markedly from day 1 to 6 of life and decreased after day 21. This decrease continued until preschool-age. The T3-value was highest in the newborns and showed no significant changes during the following ages. The higher blood levels of thyroid hormone in infants during the neonate period have to be taken into account when distinguishing between hypo- and hyperthyroid patients.


[Continuous negative pressure (cnp) in infants with idiopathic respiratory distress syndrome (irds) (author's transl)].

13 unselected premature infants with idiopathic respiratory distress syndrome (IRDS) have been treated with continuous negative pressure (CNP). A chamber was applied to the infants' body, so that the head remained outside in normal atmospheric pressure. 4 infants died during the period of treatment. 6 out of 13 differently treated IRDS-infants died over the same 6 months period. In comparison 18 out of 27 infants with IRDS died the previous year, during the same period. The frequency of IRDS in both observation periods was the same, as was the therapy of acidosis and hypoxia. The infants responded to CNP with decreased respiratory frequency, lessening of "grunting" and return of a pink skin color. Pathological examination of 3 out of 4 deceased infants in the study group revealed both atelectases and some degree of interstitial emphysema and widened capillaries. No intravascular hyaline thrombi were seen. The remaining infant died with clinical signs of coagulopathy (no autopsy). Of the 9 surviving infants in the study group one developed a hydrocephalus and subsequent mild psychomotor developmental retardation. We conclude that the CNP therapy in the chamber is an asset to the treatment of early and medium-severe cases of IRDS. We believe, that early application might prevent development of severe IRDS. The method is not recommended for severe cases.


[Neonatal information system II: computer-adapted examination form for the newborn (author's transl)].

For the documentation of the neonatal status we use computer-adapted optic mark reader forms since 1972. All important symptoms and signs are scheduled on two sheets and are assigned by pencil marking. The forms can be read automatically and are suitable for data processing. A copy remains in the patients clinical file and can be used like a conventionally written status. The mark reader forms improved singificantly our knowledge about the newborn's status. The problems of introducing the new documentation into the hospital routine are reported.


[Everyday problems of the treatments of flat feet in children (author's transl)].

There are different opinions concerning pathology and treatment of the flat foot in children in the literature as well as in practice. The practical problems of treatments are discussed. The mechanism of arch support of the foot is also touched. The authors discuss the problematic questions of treatment with reference to the literature and their own practical experience.


[Ambulatory management of the diabetic child (author's transl)].

A practical method of ambulatory management of childhood diabetes is described. The patient and his parents must realize that diabetes is a chronic disease which needs lifelong management. Adequate instruction should include the following principles of management and control: urine testing, diabetic diet, administration of insulin, intensive motor activity, recognition and treatment of hypoglycemic episodes. Hospitalisation of diabetic children should be avoided as much as possible. A proper ambulatory management of diabetic children ensures normal growth and development, that differs in no way from that of nondiabetic children.


[Isolated peroneal nerve palsy in a newborn (author's transl)].

This is a case report of a newborn infant with an isolated complet paresis of the peroneal nerve, diagnosed shortly after birth. The etiology of this quite rare observation in a newborn is discussed and the literature reviewed.


The induction by X-rays of chromosome aberrations in male Guinea-pigs, rabbits and golden hamsters. III. Dose-response relationship after single doses of X-rays to spermatogonia.

The induction by X-rays of translocations in spermatogonia was studied by cytological means in spermatocytes derived from them. In the rabbit and guinea-pig hump shaped dose-response curves were obtained, with a linear relationship at the low doses. The shapes of the curves were similar to those reported for the mouse, except that the maximum occurred at 600-700 rad in the mouse as opposed to 300 rad in the guinea-pig and rabbit. Unlike the guinea-pig and rabbit, the golden hamster showed a hump dose-response curve without a definite peak value and with little decrease in yield at high radiation doses. Over the low dose range 100-300 rad, the slopes of the curves of translocation yield were in the order:mouse (highest), rabbit, guinea-pig and hamster. Data on sterile periods suggested that the amount of spermatogonial killing in the rabbit and guinea-pig was as great or greater than in the mouse, and that in the golden hamster it was most severe. It is suggested that the differing shapes of the dose-response curves can be explained by a lower sensitivity to translocation induction in the test species and, also especially in the golden hamster, a greater sensitivity to cell killing. The possibility of extrapolating from these data to other species is discussed.


Cytogenetic analysis of X-ray-induced chromosome aberrations in spontaneously leukaemic AKR mice.

The increased frequency of numerical and structural chromosomal aberrations in spontaneously leukaemic AKR mice, compared with the values of healthy control CBA/H-T6T6 mice, induced by X-irradiation, migh be connected with the predisposition to malignant growth, probably indirectly helping the virus activation, or acting together with the immune deficiency, by creating a weaker system that is more sensitive to carcinogenic agents.


A comparison of chromosomal radiosensitivities of somatic cells of mouse and man.

A cell culture technique for quantitative analysis of radiation-induced chromosome aberrations in somatic cells has been developed and used for the comparison of chromosomal sensitivity of skin cells of mouse and man to 60Co-gamma-rays. This includes culture of irradiated tissues or cells in culture in arginine and isoleucine-deficient medium and subsequent refeeding with complete medium (CM). With this technique, radiation-induced chromosome aberrations can be analyzed selectively in the cells exposed in G1 phase and recovered at their first post-irradiation mitosis. When tested on the human embryonic cells, the dicentric yield was essentially the same whether they were skin cells irradiated in silu or cultured cells at various in vitro passages irradiated in vitro. In contrast, when studied in the skin cells irradiated in silu, mouse embryos and newborns were insensitive to the induction of dicentrics. In young mice on day II however, the sensitivity was at a level comparable to that in human embryonic cells and it was intermediate on day 4. Such embryonic insensitivity of the mouse cells was rapidly lost during serial transfer in vitro; and, when tested at 4th or later subculture generations, mouse and human cells were equally sensitive to the induction of dicentrics. These results suggest that the chromosomal radiosensitivity is essentially the same for mouse and human cells but can be modified by some biological factors, possibly DNA repair mechanisms, which differ between species as well as among the states of differentiation of particular cell types. Special attention was paid to the parellelism between the age-dependent changes in the chromosomal, mutational and carcinogenic radiosensitivities in the mouse. If this parallelism can be carried over to man, human pre-natal irradiation will not present any reduced genetic hazards.


Factors affecting the quantitation of dose-response curves for mutation induction in V79 Chinese hamster cells after exposure to chemical and physical mutagens.

Using four common mutagens, ethyl methanesulphonate (EMS), methyl methanesulphonate (mms), uv, and X-irradiation, the relationship between dose of mutagen, cellular lethality and frequency of 8-azaguanine resistant colonies in V79 Chinese hamster cells has been examined. Several factors affecting the recovery of mutants including inter and intra-clone metabolic co-operation have been quantitated and their influence on survival response curves examined. Induced mutant frequencies were assayed by two methods in situ, and after replating. After exposure to X-rays, MMS and UV a significantly higher frequency of mutants was observed in replated experiments as compared with the in situ situation, at all survival levels assayed. With EMS, an increment on replating was observed only at high survival levels. The replating data suggest that two types of azgr colonies are produced, i.e. those which contain only azgr cells and those which, due to damage segregation, contain a mixture of azgr and azg8 cells. These mixed colonies appear to be lost by metabolic co-operation when mutation frequencies are assayed in silu. The proportion of mixed to homogeneous colonies differs with different mutagens. Taking into account such factors, EMS and UV irradiation were similarly mutagenic at a given survival level, but at equitoxic doses, fewer mutants were recovered after exposure of V79 cells to MMS and X-rays.


The measurement of chemically-induced DNA repair synthesis in human cells by BND-cellulose chromatography.

Repair synthesis in human cells in tissue culture can be readily separated from semi-conservative DNA synthesis with the aid of a benzoylated naphthoylated DEAE cellulose (BND-cellulose) column. Cells are incubated with a radioactive DNA precursor during treatment with a repair-inducing agent. An inhibitor of semi-conservative DNA synthesis (hydroxyurea) is added to slow the progression of the DNA growing point. The cells are lysed and after treatment with ribonuclease and pronase the lysates are sheared and passed through a BND-cellulose column. Native DNA is eluted with I M NaCl. Any increase in radioactivity in the native DNA is due to repair synthesis and the specific repair activity (nucleotides inserted per mug of DNA) can be determined from radioactivity and absorbancy measurements. Repair can also be measured in the region of the DNA growing point by fractionation of the material eluted from BND-cellulose with 50% formamide. Repair was not detected in N-acetoxy-2-acetylaminofluorene (AAAF)-treated lymphoblasts derived from an individual with xeroderma pigmentosum although methyl methanesulfonate (MMS)-induced repair was observed in these cells.


The induction by X-rays of chromosome aberrations in male Guinea-pigs and golden hamsters. IV. Dose response for spermatogonia treated with fractionated doses.

The effect of dose fractionation on the induction of translocations by 400 and 600 rad X-rays in spermatogonia of guinea-pigs and hamsters was investigated cytologically. Three types of fractionation were used, dividing the dose into (a) two equal fractions 24 h apart, (b) two equal fractions 8 weeks apart, and (c) eight or twelve equal fractions of 50 rad, at intervals of one week. The two species responded similarly throughout, but gave lower translocation yields than the mouse. The effects of the first and third types of fractionation were similar to those described previously in the mouse, and suggested that a first radiation dose modifies the spermatogonial population so that its sensitivity to a dose 24 h later is altered, and that repeated radiation doses result in development of resistance to translocation induction. After 8-week fractionation the results suggested that in guinea-pigs and hamsters the spermatogonial population had not returned to normal by 8 weeks after the first dose, whereas in the mouse normal sensitivity had returned by this time. The results, reported previously, of single doses of X-rays suggest that the spermatogonial population consists of fractionated doses in the mouse suggest that the sensitive and resistant types represent different phases of the same cell type rather than two distinct types of cell. In the guinea-pig and hamster this question remains open.


A possible population monitoring system on environmental mutagens: statistical studies on retinoblastoma in Japan.

Because an increasing number of environmental mutagens have been detected by laboratory screening, the need to monitor human populations directly for mutational risk has been emphasized by many geneticists. They have proposed various monitoring systems but none of them has been practically applied because a large number of samples would need to be studied systematically in such systems. Recent studies by KNUDSON on some malignant tumors give hope that these diseases might be used to assess somatic mutation rates, as suggested by SUTTON (1972). According to KNUDSON, the age of first diagnosis of the diseases may be related to the annual somatic mutation rate. The ages of first diagnosis of unilateral and bilateral retinoblastomas have been compared among four university hospitals in Japan for cases since 1965. Three different types of analysis have been tried: (1) normal distribution; (2) KNUDSON's method; and (3) a modification of VERSCHUER's method for calculating penetration. The age at diagnosis of unilateral cases has fallen in the past ten years. A significant difference in the age of first diagnosis in bilateral retinoblastoma has been found in a hospital in Japan. The changes observed may result from the increased rate of somatic mutations induced by some environmental mutagens.


Cycloheximide resistance in Chinese hamster cells. II. Induction of Chm resistance in Chinese hamster cells by N-nitrosomethylurea.

Mutant Chinese hamster ovarian (CHO) cells with a resistance to 7-10(-7) and 8-10(-7) M cycloheximide (CHM) were induced at mutation rates of 1.9-5.2-10(-3) and 1.6-1.8-10(-3) respectively after treatment with N-nitrosomethylurea (NMU) at 100 mug/ml. The induced mutation rates differed by two orders of magnitude from the spontaneous rate of mutation to CHM resistance.


Cytogenetics of fetal wastage.

A consecutive series of 50 couples with a histroy of fetal wastage were studied cytogenetically with current banding technics. Fetal wastage was defined as occurring in couples who had more than two early abortions, stillbirth(s) or livebirths(s) or both of infants with multiple congenital anomalies. Three women were found to be balanced reciprocal translocation carriers; all translocations were not detectable by the conventional method but were demonstrable by current banding technics. In addition to the translocation carriers, one woman was found to be a mosaic for 45,X/46,XX/47,XXX. Four of the parents showed increased mitotic instability or chromosome breakage and rearrangement, or both. Parental chromosome abnormalities may therefore account for fetal wastage in between 6 and 16 per cent (or about one in 10) of couples having such a history. Such couples, if identified, can potentially benefit by prenatal monitoring of future pregnancies.


Artificial insemination with fresh donor semen.

A total of 141 patients received donor insemination during a 21/2-year period. Pregnancy was achieved by 57 per cent of these patients. When patients who were inseminated for less than three cycles are excluded, the pregnancy rate is 77 per cent. The mean conception time was three treatment cycles. In 69 pregnancies, the occurrence of abortion was that of the general population, and an increased male-to-female ratio was observed in the 36 live-born infants. Questionnaires sent to all couples and returned by 81 per cent indicated that donor insemination was not emotionally harmful to their marriage. Heterologous insemination is a safe, effective therapeutic alternative to adoption for selected couples.


Pascal's wager and the hanging of crepe.

Hanging of crepe refers to one type of strategy employed by physicians in communicating prognoses to families of critically ill patients. This approach offers the bleakest, most pessimistic prediction of the patient's outcome, presumably in an effort to lessen the family's suffering if the patient dies of his illness. Certain similarities exist between this technic and that used by Pascal, the 17th-century philosopher, in formulating his wager on the belief in God, in that both attempt to develop "no-lose" strategies, in which chances for "winning" are maximized. A detailed analysis of these strategies indicates that neither is truly "no-lose," and that both contain inherent disadvantages. Prognostication, an alternative approach to physician-family communication, appears to be strategically and morally superior to the hanging-of-crepe strategy.


Cyproheptadine-induced remission of Cushing's disease.

Experimental evidence suggests a central-nervous-system origin of Cushing's disease and a role for serotonin in the regulation of ACTH release. The efficacy of cyproheptadine therapy, therefore, was studied in three patients with such disease. Administration of 24 mg daily over a period of three to six months was associated with prompt and sustained clinical and laboratory remission. Lessening of the physical manifestations of hypercorticism occurred, together with marked improvement in muscular weakness. Urinary corticosteroid excretion and cortisol secretory rate returned to normal. The urinary corticosteroid response to dexamethasone (2 mg per day) became normal; a paradoxical increase followed 8 mg per day. Abnormal circadian periodicity of plasma cortisol concentrations persisted. Return of normal amounts of Stage III to IV sleep occurred in the one patient so studied, who previously had markedly decreased periods of these stages. Discontinuance of therapy in one patient was associated with return of laboratory evidence of hypercorticism.


Gastric acid secretion and lower-esophageal-sphincter pressure in response to coffee and caffeine.

Caffeine stimulates gastric acid secretion and reduces the competence of the lower esophageal sphincter in man. These effects of caffeine have been used as evidence that regular coffee should not be used by patients with peptic-ulcer disease or gastroesophageal reflux. We compared the dose-response relations of caffeine, regular coffee and decaffeinated coffee for gastric acid secretion and sphincter pressure in normal subjects. Decaffeinated coffee gave a maximal acid response of 16.5 +/- 2.6 mEq per hour (mean +/- S.E.M.), which was similar to that of regular coffee, 20.9 +/- 3.6 mEq per hour, both values being higher than that of caffeine, 8.4 +/- 1.3, on a cup-equivalent basis. Sphincter pressure showed minimal changes in response to caffeine, but was significantly increased by both regular and decaffeinated coffee (P less than 0.05). These data suggest that clinical recommendations based upon the known gastrointestinal effects of caffeine may bear little relation to the actual observed actions of coffee or decaffeinated coffee.


The primary-care practitioner -- specialist or jack-of-all trades.

Primary-care physicians, too often viewed as low-level generalists, are more appropriately thought of as specialists whose work demands specific skills. These physicians function as managers, advocates, educators, and counselors for their patients while also serving as co-ordinators of other professionals involved in primary care. The basis for education in primary care should be a recognition of the specialized nature of the work that primary-care physicians perform. Faculty members in primary-care programs should themselves be primary-care physicians; these educators deserve the same titles and status given other clinical specialists within the academic community. The setting of standards for primary-care practice and the design of research into areas such as the quality of care are tasks that should be undertaken by, or in collaboration with, physicians who are primary-care specialists.


Beta-adrenergic mechanisms in action tremor.

To study the mechanisms by which propranolol suppresses essential tremor, accelerometric recordings were made from four normal subjects and eight patients with that tremor, and small amounts of isoproterenol and propranolol were infused intravenously or into one brachial artery. Intra-arterial isoproterenol increased tremor amplitude selectively in that arm in normal subjects and in patients with essential tremor (range, 1.85 to 3.50 with mean 2.74 times the base-line level). Intra-arterial or intravenous propranolol quickly blocked the enhanced action tremor in both groups. It did not simultaneously affect the underlying essential tremor, whereas long-term oral propranolol therapy did diminish the amplitude of the essential tremor in each patient. Peripheral beta-adrenergic tremorogenic receptors function normally even in patients with essential tremor; their function is not necessary for the production of essential tremor, and the efficacy of chronic propranolol therapy in the suppression of essential tremor is not mediated via its peripheral beta-adrenergic blocking action.


Residual disability in survivors of stroke--the Framingham study.

Of 123 survivors of documented completed stroke from the Framingham Cohort, 119 received objective evaluations of functional status along with an equal number of controls matched for age and sex. Of the stroke survivors, 16 per cent were institutionalized, 31 per cent dependent in self-care, and 20 per cent dependent in mobility. In addition, 71 per cent had decreased vocational function, and 62 percent decreased socialization outside the home. Each of these frequencies was significantly greater than the corresponding rate in the control group.


Cardiac features of an unusual X-linked humeroperoneal neuromuscular disease.

To characterize an unusual, sex-linked recessive neuromuscular disease, we studied two families with 37 males who had involvement of distal leg and proximal arm muscle groups. Electromyography and muscle biopsy in five subjects showed features of both neuropathy and myopathy. Bradycardia and syncope in 15 involved subjects were associated with early death (before the age of 50 years). Electrocardiograms in 15 others showed a spectrum of atrial abnormalities that ranged from abnormal P waves to permanent atrial paralysis and from first-degree atrioventricular block to complete heart block. No patient exhibited clinical muscle disease without electrocardiographic atrial disease. Dilated, hypertrophied left ventricles with normal indexes of function were found in three cases with permanent atrial paralysis and chronic junctional bradycardia. Cardiomegaly and cardiac failure were not present in the other cases. We conclude that permanent ventricular pacing (instituted four patients) is indicated in many of these patients to prevent serious sequelae.


Clinical trials of hepatitis B immune globulin. Development of policies and materials for the 1972-1975 studies sponsored by the National Heart and Lung Institute.

Plasma from persons with high titers of hepatitis B antibody (anti-HBs) was used to manufacture one lot of hepatitis B "immune" globulin sufficient for four interlocking clinical trials of prevention or modification of hepatitis B infections. The trials were carried out in renal dialysis units, in medical personnel with accidental exposures to hepatitis B, in transfused patients, and in patients with fulminant hepatitis. A single policy board developed protocols that allowed comparisons among the four studies while respecting the unique requirements of each.


Hepatitis B immune globulin--prevention of hepatitis from accidental exposure among medical personnel.

The role of anti-HBs antibody in reducing the probability of hepatitis after accidental exposure to serum from patients with hepatitis or carriers of HBs Ag was studied prospectively among 712 medical workers. One fourth of the workers were anti-HBs positive and less than one per cent of them developed hepatitis, in contrast to 11 per cent among those who were anti-HBs negative. Three coded immune-serum globulin preparations of varying anti-HBs titer were randomly assigned. Among 251 persons passively immunized with globulin having a conventionally low anti-HBs titer, hepatitis developed in 17 (seven per cent) within six months. Comparative rates among those receiving intermediately high titer and high titer globulin, respectively, were five per cent (11 of 208) and two per cent (5 of 253). The significantly lower incidence among the latter (P less than 0.05) was offset by six additional cases, all in recipients of high titer globulin, detected when follow-up was extended to nine months.


Articular lesions in experimental Erysipelothrix insidiosa infection in rats.

Articular lesions were studied in the extremities and vertebral column in murine erysipelas infection. Pathologic alterations found in those different joint systems were essentially the same in character. In the early stage of infection, phlegmon-like inflammation was observed in the periarticular loose connective tissue. Abundant fine Gram-positive bacilli were free in inflamed edematous tissue. Then, active serofibrinous exudation and emigration of leukocytes occurred in the synovial membrane, articular cartilage, annulus fibrosus, and nucleus pulposus with the development of the disease. These exudative changes disappeared gradually. Instead of them, proliferation of synovial cells accompanied by dense infiltration with lymphocytes and plasma cells became conspicuous. At the same time, chondro- and osteoclastic activity occurred in the joints of the extremities or regions adjacent to the intervertebral disk. Capsular and subchondral pannus often resulted from an excessive proliferation of granulation tissue. In the late stage, they synovial membrane and granulation tissue underwent fibrosis, adhesion and ossification. Finally, these changes resulted in fibrous or bony ankylosis and deformation. Gram-positive bacilli were hardly detected in histological preparations derived from animals in the chronic stage when proliferative change was predominant in the articular lesions.


Role of testosterone in the early stage of spermatocytogenesis in rats.

The role of testosterone in the early stage of spermatocytogenesis was investigated in newborn rats. The testes of rats, either 0 or 6 days of age, were implanted into those of hypophysectomized adult rats that had or had not been injected with testosterone propionate (TP) after hypophysectomy and also into those in intact adult rats. All the animals were autopsied 17 or 11 days later when the implanted testes reached 17 days of age. The implanted testes were examined for cellular components in the seminiferous tubules. In an additional experiment, newborn rats were injected with TP or cyproterone acetate, an antagonistic substance against androgen, daily for the first 17 days of life and examined for testes. Proliferation of supporting cells and development of seminiferous tubules were less remarkable in the testes of newborn rats which had been implanted into the testes of hypophysectomized rats than in those which had been implanted into the testes of intact adult rats. Proliferation of supporting cells was not stimulated by TP, but development of seminiferous tubules was slightly promoted. Progress in spermatocytogenesis from gonocytes to pachytene primary spermatocytes was observed in the testes of newborn rats which had been implanted into the testes of hypophysectiomized rats. It was not so marked after injection with TP. These results suggested that testosterone might have stimulated development of seminiferous tubules and maturation of spermatocytes in the early stage of spermatocytogenesis by its synergistic action with a gonadotropin, possible follicle-stimulating hormone.


Effects of prostaglandins F2alpha and E1 on the longitudinal and circular smooth muscle of the guinea pig caecum in relation to the concentration of extracellular calcium.

Responses of the longitudinal and circular smooth muscle of the guinea-pig caecum were studied in media with different concentrations of extracellular calcium. A sucrose-gap method was used to record the electrical and mechanical parameters of smooth muscle activity. In the longitudinal smooth muscle no difference in the action of PGF2alpha and PGE1 was seen at low (0.8 mM), Normal (2.5 mM) or high (7.5 mM) concentrations of Ca2+. Both PG's stimulated the longitudinal strip and the action of acetylcholine at normal Ca2+ concentration was slightly inhibited immediately after the superfusion with the PG's and augmented thereafter. In the circular strip no significant difference between the stimulatory effect of PGF2alpha, and PGE1 in low and high Ca2+ solution was found. However at 2.5 mM Ca2+ PGF2alpha evoked much greater stimulation of the circular strip than did PGE1. After the end of the superfusion with either PG the effect of acetylcholine was inhibited by either PG at low Ca2+ level and potentiated at high Ca2+ level the effect of acetylcholine was inhibited by PGE1 but not by PGF2alpha. Thus, the effects of PGF2alpha and PGE1 on the circular smooth muscle differed from each other in their dependence on the concentration of extracellular calcium.


On the formation of adrenergic amine storage granules as measured by reserpine labeling.

Reserpine appears to be bound specifically and irreversibly to amine storage granules in the adrenergic neuron. The presence of reserpine persistently attached to amine granule should reflect the life span of the vesicles, and any additional binding of reserpine should then measure the rate of appearance of newly formed amine granules. Measurement of the persistent binding of tritiated reserpine (3H-Reserpine) in hearts of rats given labeled compound at various times after a saturating dose of unlabeled reserpine showed that the recovery of 3H-reserpine binding capacity occurred rapidly. Four days after reserpine the 3H-reserpine binding was 30% of control rats. The rate of return of binding capacity was then slowed being 65% of normal in 24 days. Calculation of the mean daily increment of binding capacity showed that the rate was an inverse linear function of the binding capacitu existing in the neurone at an early phase (1--8 days) but became constant at a later interval (8--24 days). It is suggested that the return of reserpine binding capacity reflects the appearance of new storage granules and that the rate of storage granule synthesis in the cell body is under feedback control. The signal for enhanced granule formation does not appear to be related to the intensity of nerve traffic not to the concentration of transmitter in the neuron since manaeuvers which alter these parameters did not change the rate of reserpine binding recovery.


The action of gantrisin [N'-(3,4-dimethyl-5-isoxazolyl)sulfanilamide] on the oedema-forming and muscle-stimulating activity of eledoisin and physalaemin.

The effects of gantrisin on oedema-forming and muscle-stimulating activity of eledoisin and physalaemin were studied. Both in vivo and in vitro the sulfanilamide caused a dose-dependent inhibition of the peptides' effects. The antagonism appeared to be of the non competitive as well as of the non specific type.


Adrenoceptors in cardiac ventricular muscle and changes in duration of action potential caused by noradrenaline and isoprenaline.

1. On guinea-pig papillary muscle we investigated whether a prolonging effect of noradrenaline on the duration of the cardiac ventricular action potential (AP) is attributable to an action on beta-adrenoceptors. 2. Propranolol (5 X 10(-6) M), which itself shortens AP (at 90% repolarization level), inhibits both effects of noradrenaline on the AP, i.e. the sustained prolongation by low concentrations (10(-7)--10(-6)M) and the steady-state shortening which follows an initial prolongation by a high concentration (10(-5)M). In the presence of propranolol, the prlonging effect of noradrenaline is shifted to higher concentrations (10(-6)--10(-5)M). This prolongation of AP duration does not exceed the prior shortening effect by propranolol; it is not prevented by 10(-5)M phentolamine. 3. Phentolamine, which itself prolongs AP duration, inhibits neither the initial prolongation nor the steady-state shortening of the AP by 10(-5)M noradrenaline. Instead, the biphasic change in AP duration as well as the positive inotropic effect of 10(-5)M noradrenaline are enhanced in the presence of 3Z10(-6)M phentolamine. 4. The effect of isoprenaline on the duration of AP qualitatively resembles that of noradrenaline. In a concentration of 10(-8)M, isoprenaline produces a sustained prolongation of the AP; concentrations of 10(-7)M and 10(-6)M cause an initial prolongation which is followed by a steady-state shortening. These effects are inhibited by propranolol. 5. It is concluded that not only the steady-state shortening effect on AP duration by 10(-5)M noradrenaline but also the prolongation of AP, induced by lower noradrenaline concentrations (10(-7)--10(-6)M), are mediated solely by an action on beta-adrenoceptors.


Influence of morphine and naloxone on the release of noradrenaline from rat cerebellar cortex slices.

In slices of rat cerebellar cortex preincubated with (-)-3H-noradrenaline, the influence of morphine and naloxone on the efflux of tritium was investigated. The spontaneous outflow was not changed by 10(-5) M of either morphine or naloxone. On the other hand, morphine caused a concentration-dependent decrease of the overflow of tritium evoked by electrical field stimulation. Naloxone did not change the stimulation-induced overflow, but prevented its inhibition by morphine. It is concluded that morphine, through an action on opiate receptors located on cerebellar noradrenergic neurones, inhibits the secretion of the transmitter in response to nerve impulses.


Influence of ouabain and dihydroouabain on the circular dichroism of cardiac plasmalemmal microsomes.

1. The influence of ouabain on the tertiary structure of cardiac plasmalemmal proteins was investigated by means of circular dichroism measurement. Purified plasmalemmal microsomes were obtained by sucrose gradient centrifugation. The CD-spectra of the membranal proteins were shifted to the red and the amplitudes were smaller than those of the same proteins after solubilization. 2. Ouabain induced an increase of the ellipticity bands at 210 and 222 nm of about 50% above the level yielded with microsomes after sonication. At 222 nm ouabain exhibited the half maximum effect at a concentration of 5 X 10(-9) M. The effect could, however, only be exerted if the inside of the microsomes was exposed to ouabain by sonication, thus reflecting the inside-out nature of the plasmalemmal microsomes. 3. The high specificity of the ouabain effect was underlined by the following experiments: a) Dihydroouabain, a much less cardioactive derivative of ouabain proved to be ineffective in corresponding concentrations, b) ouabain had no influence upon the CD spectrum of microsomes derived from cardiac sarcoplasmic reticulum, c) a detergent-like action of ouabain underlying the observed effect can be excluded since highly active tensides, i.e. desoxycholate and dodecylsulfate, only influence the CD spectra at concentrations exceeding 10(-3) M, d) electronmicrographs of microsomes exposed to ouabain demonstrated no alteration of either the appearance or size of the microsomes. 4. The magnitude of the observed ouabain effect indicates that a large portion of the membrane-bound proteins is involved. The number of binding sites and their isolated structural alteration induced by ouabain are not sufficient to account quantitatively for the enhanced amplitudes of the CD spctra. This suggests that ouabain evokes structural changes of membrane proteins different from actual binding sites. It seems, therefore highly improbable that changes of the Na-K-ATPase present in the plasmalemmal microsomes are responsible for the observed effect.


Effects of nifedipine, a potent calcium-antagonistic coronary vasodilator, on atrioventricular conduction and blood flow in the isolated atrioventricular node preparation of the dog.

The effects of the calcium-antagonist nifedipine on atrioventricular (A-V) conduction and blood flow were investigated in comparison with those of verapamil by the use of the isolated, arterially blood-perfused A-V node preparation of the dog. Single injections of 0.3--30 mug of nifedipine and verapamil into the A-V node artery produced a dose-related increase in the A-V conduction time and at 30 mug the two drugs caused second degree block of A-V conduction. The results are compatible with the hypothesis that a slow calcium channel plays an important role in excitation of A-V nodal cells. The rate of blood flow through the A-V node artery was about 10 times more sensitive to nifedipine than was the A-V conduction time and increased in a dose-related manner. In contrast, an increase in blood flow rate by verapamil occurred in almost the same dose range as did impairment of A-V conduction. This indicates that the action of nifedipine is more pronounced on coronary smooth muscle cells than on the A-V nodal cells.


Action of D-600 on spontaneous and electrically stimulated activity of the parturient rat uterus.

The effects of D-600, the methoxy derivative of verapamil, on the parturient rat uterus have been studied. At concentrations of 10(-8) to 10(-7) M, D-600 abolishes spontaneous contractions and reduces the force of electrically evoked contractions. The first action is associated with a reduction in amplitude of the slow waves (oscillations of membrane potential which underlie rhythmic bursts of spikes initiating contractions). The second is associated with a reduction in frequency of spikes within the bursts accompanying the electrically stimulated contractions. This reduction results from a decrease in the slope of the prepotential in cells in pacemaker areas of the muscle. D-600 also decreased the height and rising velocity of the conducted action potentials, but these actions cannot account entirely for the reduction in contractile force.


Effect of ryanodine on myocardial calcium.

The effects of ryanodine and ryanodine steady-state condition (RSSC) on contractile-related calcium were examined in isolated guinea pig left atrial muscle. 1. RSSC is a specific irreversible condition occurring after a brief exposure to 1 x 10(-7) M ryanodine, followed by washing. It is characterized by elimination of the contraction following a 10-sec rest interval (post-rest) and prolongation of the associated action potential duration (AP50%) from 78.9 to 160.8 msec with minimal alteration in steady-state tension development determined at 1 Hz. 2. Induction of RSSC with a ryanodine-bovine serum albumin conjugate produced similar alterations in post-rest contractile strength and action potential duration. 3. In the presence of 1 x 10(-7) M ryanodine, guinea pig left atria exhibit a significant increase in total 45Ca efflux from two rapidly exchangeable compartments (compartment 1, t1/2=1.58 min; compartment 2, t1/2=8.20 min). 4. In atria loaded after the induction of RSSC, total 45Ca release was significantly reduced by 7.2% of the total exchange. 5. The 45Ca exchange space for RSSC atria was reduced from 23.22 +/- 0.81 to 19.85 +/- 1.22 ml per 100 g muscle without a significant reduction in the total exchange space. 6. From these results, it is concluded that the effects of low concentrations of ryanodine and RSSC are to alter the contractile calcium levels of the tissue, primarily from sarcolemmal membrane sites which regulate post-rest contractile strength and action potential duration.


Inotropic and electrophysiological actions of verapamil and D 600 in mammalian myocardium. I. Pattern of inotropic effects of the racemic compounds.

A pattern analysis of inotropic actions was carried out on isotonically chortening cat papillary muscles exposed to (+/-)-verapamil and (+/-)-D 600 and compared to other Ca-antagonistic interventions. 1. (+/-)-Verapamil (1--5mug/ml) leaves contraction amplitudes nearly unchanged at 6/min, whereas at 60/min more than 90% depression (5 mug/ml) occurs. (+/-)-D 600 is about twice as effective as (+/-)-berapamil. 2. An increase of [Ca2+]O in the presence of (+/-)-verapamil or (+/-)-D 600 does not restitute the normal amplitude-frequency relationship. There is only a shift toward higher contraction amplitudes. 3. (+/-)-Verapamil and (+/-)-D 600 lead to typical biphasic inotropic transients after step changes of the friving rhythm. First a fast and (at higher frequencies) very pronounced negative staircase occurs, followed by a rather slowly developing positive staircase. 4. These drug effects contrast to the effects of lowering [Ca2+]O or of adding Ni2+ or La3+, which all produce a rather uniform depression of contraction amplitudes at all frequencies and do not elicit staircase phenomena such as seen under the influence of (+/-)-verapamil or (+/-)-D 600. 5. In contrast to the action of Ni2+, La3+ or low [Ca2+]O, (+/-)-verapamil slows down the restitution kinetics of Ca-reavailability from internal stores as determined by the amplitude of test contractions elicited after various periods of rest. 6. Drug-induced changes in the time course of the transmembrane action potential as depending on frequency may partially but not fully explain the contractile phenomena. 7. Possible interpretations as to the sites where (+/-)-verapamil or (+/-)-D 600 interferes with cardiac excitation-contraction coupling are given by the aid of a multicompartment model. This model describes excitation-contraction coupling in terms of transmembrane and intracellular Ca-movements.


Inotropic and electrophysiological actions of verapamil and D 600 in mammalian myocardium. II. Pattern of inotropic effects of the optical isomers.

On isotonically contracting cat papillary muscles analysis, a comparison of the effects of the optical isomers of verapamil and D 600 and the racemic drugs was performed. 1. (-)-verapamil (0.2-3.0 mug/mo) and (-)-D-600 (0.1 mug/ml-3.0 mug/ml) leave the steady state contraction amplitudes nearly unchanged at 6/min, but produce a strong depression at 60/min. (-)-D 600 is about 8 times as effective as (-)-verapamil. The (+)-isomers exert only a moderate negative inotropic effect (particularly at low frequencies). 2. Increase of [Ca2+]O does not restitute the normal amplitude-frequency relationship during exposure to either the (-)-isomers or the (+)-isomers. 3. The (-)-isomers lead to typical biphasic staircases after step changes of frequency. A fast negative staircase occurs first followed by a rather slowly developing positive staircase. In contrast, the (+)-isomers have little influence on the usual staircase pattern. 4. The strength-interval relationship for single test contractions elicited after frequent conditioning stimulation indicated that the (-)-isomers probably slow the restitution of intracellular Ca-reavailability. The (+)-isomers have no such effects. 5. The effects produced by the (+/-)-compounds correspond qualitatively to those of the (-)-isomers. 6. The very different patterns of inotropic actions observed indicate that the (-)- and (+)-isomers of verapamil and D 600 probably interfere with cardiac excitation-contraction coupling at different sites.


Inotropic and electrophysiological actions of verapamil and D 600 in mammalian myocardium. III. Effects of the optical isomers on transmembrane action potentials.

Excitability, maximum velocity of depolarization (MVD), conduction velocity, discharge rate and the duration of transmembrane action potentials as a function of frequency of stimulation were studied in isolated cardiac tissues exposed to the optical isomers of verapamil and D 600.