Pre and postoperative ventricular function in infants and children with right ventricular volume overload. Hemodynamic and ventricular volume parameters were evaluated in 21 patients (24 studies) with total anomalous pulmonary venous return (TAPVR), 11 patients with secundum atrial septal defect (ASD), and eight patients who had complete correction of TAPVR or ASD. Right and left ventricular (RV and LV) volume parameters were calculated according to Simpson's rule and the area length methods, respectively. In infants with TAPVR, RV end-diastolic volume was larger than normal, but RV ejection fraction was significantly less than normal. LV end-diastolic volume and LV ejection fraction were all less than normal in infants with or without pulmonary hypertension, and the values did not correlate with the cardiorespiratory symptoms. In children with TAPVR or ASD, RV end-diastolic volume and output were higher than normal preoperatively and decreased to normal or near normal values postoperatively. The data suggest that pulmonary venous obstruction and/or RV failure are responsible for cardiorespiratory symptoms in infants with TAPVR and early surgical intervention is recommended in these patients.


Late development of pulmonary venous obstruction following Mustard's operation using a dacron baffle. Three patients developed late pulmonary vein obstruction (PVO) following Mustard's operation for transposition of the great arteries. In all three the absence of PVO had been documented by an earlier postoperative cardiac catheterization. At reoperation shrinkage and kinking of the dacron baffle was evident. After Mustard's operation, patients should be observed closely for symptoms and signs of PVO since it can occur insidiously despite previously proven absence of this complication.


Quantitation of left ventricular myocardial fiber hypertrophy and interstitial tissue in human hearts with chronically increased volume and pressure overload. Using new techniques, we quantitated left ventricular myocardial fiber hypertrophy and interstitial tissue in four groups of autopsied hearts free of coronary disease: 1) 22 normal hearts, 2) 20 hearts from patients with mitral incompetence (NYHA Class II-III) who died early after mitral valve replacement from causes other than cardiac failure, 3) 22 hearts from patients with mitral incompetence (NYHA Class III-IV) who died early after mitral valve replacement from cardiac failure with low cardiac output syndrome, and 4) 22 hearts from patients with hypertensive heart disease (NYHA Class II-III). Myocardial fiber hypertrophy was quantitated by measuring cross-sectional myocardial fiber diameter; the proportion of interstitial tissue was quantitated by using a computerized, high-resolution video image-digitizing system. Myocardial fiber average diameter in groups 2, 3 and 4 was significantly higher than group 1. The proportion of interstitial tissue was significantly increased in group 3. In chronic mitral incompetence an increase in left ventricular interstitial tissue may play a role in the development of severe cardiac failure.


Distance correction for precordial electrocardiographic voltage in estimating left ventricular mass: an echocardiographic study. This study was undertaken to assess both the relation between echocardiographic measurement of left ventricular (LV) mass and commonly used electrocardiographic criteria for LV hypertrophy and the effect of the distance from the center of LV mass to the anterior chest wall on precordial voltage. Echocardiograms and standard 12-lead electrocardiograms were obtained on 100 persons, ages 3 to 79. The correlation coefficients of echocardiographically determined LV mass with ECG precordial voltage (SV1 + RV5 or V6), the Estes point score system, and a VL4 wave voltage were .686, .721, and .531, respectively. Extrapolating from the dipole nature of the heart, the precrodial voltage was multiplied by the square of the chest wall to mid-LV distance to correct for the loss of energy across the distance from LV to recording electrode. Utilizing this correction, a much improved precordial voltage estimation of LV mass (r = .846) was obtained. We conclude that the distance of the center of LV mass from the chest wall influences the amplitude of recorded precordial voltage and that correction for this influence improved the correlation of precordial voltage with LV mass.


Left ventricular mechanical efficiency in man with heart disease. Thirty-eight adults with valvular and/or myocardial disease had heart catheterization with coronary blood flow and myocardial O2 consumption (MVO2) per 100 g measured by the nitrous oxide washout technique. Quantitative biplane angiocardiography was performed to assess left ventricular volume, mass, ejection fraction and work. Left ventricular efficiency was calculated from work, MVO2/100 g and mass. Efficiency ranged from 4 to 40% and was normal in some patients with severe ventricular pressure-volume work overloads. Total left ventricular MVO2 ranged up to 461 ml/min. Neither total MVO2 nor MVO2/100 g was significantly related to ventricular work, ejection fraction, or tension-time index. These data suggest 1) a relationship between left ventricular efficiency and myocardial function in chronic valvular or myocardial disease, 2) that efficiency may be normal in hypertrophied ventricles, and 3) that chronic increases in resting ventricular metabolic requirements are met by hypertrophy rather than by increased MVO2/100 g.


Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. An accurte echocardiographic (E) method for determination of left ventricular mass (LVM) was derived from systematic analysis of the relationship between the antemortem left ventricular echogram and postmortem anatomic LVM in 34 adults with a wide range of anatomic LVM (101-505 g). No subject had massive myocardial infarction, ventricular aneurysm, severe right ventricular volume overload or hypertrophic cardiography. The best method for LVM-E identified combined cube function geometry with a modified convention for determination of left ventricular internal dimension (LVID), posterior wall thickness (PWT), and interventricular septal thickness (IVST), which excluded the thickness of endocardial echo lines from wall thicknesses and included the thickness of left septal and posterior wall endocardial echo lines in LVID (Penn Convention, P). By this method, anatomic LVM = 1.04 ([LVIDp + PWTp + IVSTp]3--[LVIDp]3) -- 14 g; r = 0.96, SD= 29 g, N= 34. Standard echo measurements gave less accurate results, as did previously reported methods for LVM-E. LVM-Dp is an accurate, widely applicable method for the study of left ventricular hypertrophy.


Nonenzymic spectrophotometric determination of potential poison ivy cross-reactors. I describe an inexpensive, nonenzymic analytical system for prescreening substances that might cross-react as Rhus toxing (e.g., poison ivy, poison oak, and sumac allergens) on human skin. By spectrophotometric assay after incubation with an oxidizing mixture of Cu(II)ammine complex and ammonium persulfate, I could accurately and reproducibly determine o-quinoidal products of several potential synthetic cross-reactors and native poison ivy allergen, and could distinguish these from catecholamines, resorcinol, p-hydroquinone, and a closely related phenol. A good correlation was obtained between this nonenzymic technique and an enzymic assay. This Cu(II)ammine/persulfate oxidative assay, however, is inexpensive and obviates any spectral interference from enzymic proteins.


Down syndrome due to partial trisomy 21q. A patient is reported with a typical Down syndrome phenotype, caused by patrial trisomy of chromosome 21. Based on the present case and data from the literature, it is suggested that the Down phenotype is due to the trisomy of the distal portion of the band (q22) of chromosome 21.


Partial trisomies of chromosome 21 in man. Two new observations due to translocations 19;21 and 4;21. Partial trisomy of the distal portion of the long arm of chromosome no. 21, resulting from a (familial) translocation between the chromosomes no. 19 and 21 in a female twin with Down's syndrome, supports the hypothesis that triplication of 21q22 is the cause of the physical signs of mongolism. Partial trisomy of the remaining segments of chromosome no. 21 due to a (familial) translocation between the chromosomes no. 4 and 21, however, may only cause mental deficiency.


Two cases of Down syndrome with unusual de novo translocation. Two children with the clinical features of Down syndrome were found to have several unusual cell lines. In both cases the same reverse tandem translocation between two 21 chromosomes was present in one line. This may be an unstable rearrangement. In addition, the findings offer some support for current efforts to localize the portion of chromosome 21 responsible for clinical features of Down syndrome to band 21q22. Acridine orange R banding was found to be especially useful in the identification of the break points on the translocations. The origin of the abnormality was found to be paternal in one case and was indeterminate in the second.


Cosmetics, the consumer, the factory worker and the occupational physician. Suggestions concerning ways to determine untoward dermatologic effects of cosmetics. Methods for investigating contact eczematous patients and for measuring the sensitizing potential of various substances are well known and in general, sufficiently effective. This is not true for irritant dermatitis, or for possible (skin) irritant substances; moreover, cosmetics commonly do not contain acutely harmful ingredients. The use of various instrumental measurements (insensible H2O loss, CO2 release, electrical impedance, sweat rate) as indicators of the irritant potentials of substances is advocated. At the same time it is suggested that the factory physician actively investigate the workers in his factory, since these workers are exposed to known substances in known concentrations and combinations, possibly for extensive periods. This may prove to be part of a new role for him. A cosmetic may be one of several factors increasing impairment and only beyond a certain limit may this result in overt disease. Below that limit the health reserve is only partially depleted. Whether this is harmful to a person depends on other stresses, such as medicaments, work materials, other cosmetics and environmental chemicals. The effect of these must also be quantified. A model of these cumulative stresses and reactions is presented and discussed.


Contact dermatitis in a spinal injuries centre. A routine patch testing survey carried out on 122 patients in the National Spinal Injuries Centre at Stoke Mandeville Hospital showed that 40.1% of the patients studied gave positive patch test results to medicaments and other topical applications. The incidence of positive results was higher in patients with a history of pressure sores (45.1%) than in those who had never had sores (33.3%). The significance of these results is discussed.


Occupational dermatoses among foresters. The incidence of occupational dermatoses among the forest workers of a timber company has been investigated. In the survey 73.69% of the occupational dermatoses observed were contact dermatitis, predominantly due to sawdust and sap. Insect bites, mycotic infections and staphylococcal and streptococcal infections were seen. The results of the survey and preventive measures are discussed.


Skin hazards from nickel and chromium salts in association with cutting oil operations. Under ordinary working conditions in which grinding fluids were used, the presence of nickel or chromates was not detectable by spot testing. Laboratory studies, however, indicate that nickel can be leached from the machined metals.


Nickel allergy and atopy in hairdressers. A study of 35 hairdressers with hand eczema was made during an 18-month period. A total of 29 were test-positive to one or more substances in the standard series and/or to products from their working environment. 40% were allergic to nickel. The prevalence of personal atopy was higher in the nickel-negative than in the nickel-positive. Immunoglobulin E determination was not of assistance in attempts to differentiate between nickel-positive and nickel-negative hairdressers. In 72% the eczema had started before the age of 25 and in 23% after less than 1 year in the profession. The desire is expressed that all hairdressing products shall be labelled in respect to allergen contents, since 46% of the hairdressers reacted to one or more such agents.


Allergic contact dermatitis from cardamom. A case is presented of a confectioner with a chronic hand dermatitis and positive patch test reactions to cardamom and certain terpenoid compounds present in the dried ripe seeds of cardamom. Cardamom is a popular traditional flavouring agent for baked goods and confectionery. Dermatitis from skin exposure to cardamom has to the best of our knowledge not been reported. We report one case of allergic contact dermatitis to cardamom elicited by terpenes present in the seeds.


Hexahydro, 1,3,5, tris (2-hydroxyethyl) triazine, a new bacteriocidal agent as a cause of allergic contact dermatitis. During the investigation of an outbreak of dermatitis in a medium-sized engineering works, the authors discovered four patients with allergic contact sensitivity to hexahydro,1,3,5, tris (2-hydroxyethyl) triazine, (Grotan), a new bacteriocidal agent used in coolant liquids. The authors failed to find any published report on this subject and would like to draw attention to Grotan as a new potential sensitizer.


Occupational eczema from para-tertiary-butylphenol formaldehyde resins: a review of the sensitizing resins. The first case of allergy due to para-tertiary-butylphenol formaldehyde resins (PTBP resins) were found in 1958 in the shoe-making industry. These resins are found in certain neoprene adhesives. PTBP resin hypersensitivity may be due either to the para-tertiary-butylphenol, to the resin itself or less frequently to the formaldehyde. These resins may cause occupational allergy (in the automobile industry and chiefly in the shoe-making industry) and non-occupational allergy (footwear and clothing hypersensitivity). Patients allergic to PTBP resins have been found to show a cross-reaction to other resins such as Alresen PA 103, Schenectady SP 126 and Schenectady SP 154. The authors give a reference list of sensitizing neoprene adhesives and PTBP resins so that manufacturers can limit the use of these products as far as possible.


Contact dermatitis from radiata pine.

Contact dermatitis from radiata pine. Sawdust from radiata pine trees which are grown extensively throughout South Australia causes various forms of contact dermatitis. The various forms are described in nine cases which illustrate that the early diagnosis of industrial dermatitis is necessary to prevent the condition from becoming chronic. A chance association between colophony in radiata pine sawdust and colophony in adhesive plaster, which caused contact dermatitis when used in patch testing, led to the discovery of these cases.


Compositae sensitivity among patients with contact dermatitis: value of compositae oleoresins in a standard test series. Patch tests with 24 Compositae species were performed on 81 patients suspected of having a plant dermatitis, of whom 16 had positive reactions to various species. When Compositae were included in the standard series, 10 of 488 consecutive patients (2%) were found to be sensitive to one or more species. Most of the positive test reactions were relevant. Fourteen of 16 sensitivities could have been detected by testing with two mixtures of Compositae. Alantolactone could not serve as a screening agent, since four of seven Compositae-sensitive patients had negative reactions to it. Concomitant reactions to balsams were found in four of 10 patients with unexpected sensitivy to Compositae. The clinical pattern of Compositae dermatitis may be that of a lichenified photo dermatitis. These cases are invariably missed, unless patch tests with Compositae are performed. Another group of patients have hadn eczema and also require patch tests with Compositae for etiological diagnosis. Because positive, relevant reactions are common, inclusion of a safe and reliable Compositae screening test in the standard series is urgently required. At the present stage, however, our test materials are sometimes irritant and they have occassionally caused active sensitization.


Contact dermatitis from tromantadine hydrochloride. Of 240 patients treated with 1% tromantadine hydrochloride ointment, 20 showed local irritation, of which 12 were due to contact allergy as demonstrated by patch testing.


Benzoyl peroxide gel in acne therapy.

Benzoyl peroxide gel in acne therapy. A micronized benzoyl peroxide, in a magnesium aluminum silicate-alcohol gel, appears to achieve dramatic objective improvement of the comedo and papular stages of acne, as well as associated seborrhea. Burning sensations and excessive erythema, found with similar modalities, have been virtually eliminated.


Parenteral short-term corticosteroid therapy in moderate to severe dermatoses. A comparative multiclinic study. Six separate investigators following the methodology stipulated in a common protocol provided a data base of 124 patients with Rhus dermatitis, other contact dermatitis, or atopic dermatitis. In this double-blind study, one or two 1 ml (4.0 mg/ml) intramuscular injections of the new sodium phosphate ester of betamethasone was compared with dexamethasone sodium phosphate in the treatment of the signs and symptoms common to these disorders. The comparably balanced groups responded dramatically to both drugs. Within 24 hours the mean scores of all symptoms and patients' overall condition were reduced appreciable. Pruritus, burning, inflammation and other typical symptoms and signs each responded well. The significant beneficial differences were observed most often in patients on betamethasone. There were no treatment failures and no side effects in this short-term trial.


Non-comedogenic cosmetics.

Non-comedogenic cosmetics. The need for a "comedogenic-free" cosmetic for acne patients led to this study using the only available mode, the rabbit. To facilitate the formulation of this benign cover-up, a range of cosmetics and ingredients was tested. Many cosmetics, fractions, and modifications of lanolins were comedogenic, as were emulsifiers such as butyl sterate, isopropyl myristate and sodium lauryl sulfate. From this data we incorporated non-comedogenic, into an acceptable cosmetic formulation for patients. The use of this formulation in susceptible acne-prone women reduced the rate of "acne cosmetica" in our clinic patients from 25% to less than 5%. We were unable to confirm a recent study suggesting that sulfur was a potent acnegen.


Adolescent skin problems.

Adolescent skin problems. The most common dermatoese encountered in the adolescent-acne, seborrhea, neurodermatitis, contact dermatitis, warts pyodermas, fungal infections and venereal disease-are discussed. Specific treatments are described, and proprietary preparations are indicated.


Systemic drug rashes: pitfalls in diagnosis and treatment. Some of the unusual findings in eruptions from systemically administered drugs are localization to areas of trauma and localization in the mucosae. Systemic drug eruptions must be distinguished from autosensitization eczema, lesions produced by scratching, by application of drying preparations and from all the other causes of sudden widespread erythema. A calendar of the dates on which all the drugs were given is suggested to help find the causative drugs. In general, almost all drugs should be stopped and a period of time should be allowed to pass before a decision is made as to whether or not a particular drug can be implicated. Rarely, coricosteriods will have to be given. Consultation with physicians who have day-to-day experience in handling systemic drug reactions should be obtained if you are not sure of the diagnosis or management.


Acne enigmas and some pure hypotheses about them. The enigmas of why acne usually starts and stops at certain ages, why and how it so often cures itself, are recalled and some explanatory hypotheses are mentioned. Certain other enigmas are mentioned including why some patients have much oil and little acne, and some vice versa; why some blackheads and whiteheads initiate inflammation and suppuration and others not; why cysts and why scars form in some patients and not in others. Enigmas such as these show that acne is not only a common disease that supplies the practitioner's bread and butter, but one offering almost unequaled opportunities for research.


A microbial etiology of acne?

A microbial etiology of acne? The view is advanced that sebum as originally produced must contain materials, other than lipids, which may serve as a selective substrate for growth of bacteria and yeasts. Growth of large numbers of P. acnes and P. granulosum in some follicles is considered to place those follicles at risk of undergoing pathological changes. Deleterious products of bacterial growth could be not only lipase and free fatty acids, but also other enzymes as well as bacterial antigens and unspecified toxins or irritants. The possibility is suggested that follicles heavily infested with P. acnes and P. granulosum may be identified by their reddish fluorescence under ultraviolet light, thus permitting identification and study of those which are at risk. Antibiotics may be helpful in reducing the formation of harmful bacterial products during continued growth of the organisms. The eventually self-limiting nature of the disease may be due to the immune response to bacterial products, or to an accommodation of the follicular epithelium to the long-continued presence of irritant materials within the follicle.


Acne from an immunological perspective.

Acne from an immunological perspective. Patients with acne vulgaris, particularly those with severe inflammatory forms of the disease, are known to have high titers of serum antibodies, and intensified immediate hypersensitivity reactions to P. acnes antigens. The significance of this fact has not been clarified, but it is possible that antigen-antibody reactions involving P. acnes in the perifollicular dermis could intensify the inflammatory response in certain forms of acne. Further studies utilizing newer, more sophisticated techniques are needed to identify the role of P. acnes antigens in affecting such fundamental phenomena as chemotaxis, cell-mediated immunity, activation of the complement cascade and reticuloendothelial system stimulation. Answers to these basic questions have the pathogenesis of that common but even more complex disease, acne.


Acne vulgaris. Studies in pathogenesis: suppression of nonspecific esterases. Oral tetracycline eliminated the histochemical staining for nonspecific esterase in human sebaceous glands after two weeks of administration. This evidence offers further support for the hypothesis that the clinical benefits of tetracycline result from suppression of follicular esterase-lipases, probably those from C. acnes.


Topical treatment of acne with a tetracycline preparations: results of a multi-group study. This report presents the results of a 13-week study done on 300 patients with acne vulgaris treated with a tetracycline topical lotion alone. The vehicle used was an aqueous-ethanol solution containing the penetration enhancer, n-decyl methyl sulfoxide. On a 0-8 grading scale, 81% of the patients improved by one or more grade points, 57% by two or more points and 31% by three or more points. Analysis indicated that concomitant variables such as severity, age, type of acne, sex and season of the year did not alter the conclusion as to efficacy. Detailed statistical analysis indicates that the conclusion is valid that the tetracycline preparation is beneficial in the treatment of acne vulgaris. No adverse reactions were observed in the patients treated. Hemograms, blood studies and urinalyses were completed on 37 patients. No disturbing trends were uncovered.


Scanning electron microscopic study of tretinoin (vitamin A acid) acne therapy. Structural differences between untreated and tretinoin treated acne, uniquely evident with the scanning electron microscope, provide insight into the disease and its response to the drug. Early tretinoin therapy is characterized by the appearance of loosely adherent, parakeratotic cells which account for comedo expulsion and a disrupted skin surface. Persistence of the follicular and comedonal alterations account for the prophylactic value of long-term therapy. Meanwhile, the structure of the stratum corneum returns toward normal, with the clinical accommodation to the topical tretinoin.


Antibiotic resistant acne.

Antibiotic resistant acne. Our approach to a patient who fails to respond to antibiotics is as follows: First, take a careful history. Look for use of cosmetics and topical corticosteroids, anticonvulsive agents and systemic corticosteroids. Inquire about marked increases in emotional or psychological stresses accompanied by noticeable seborrhea. Probe the patient about habits of leaning on or squeezing acne areas, and most importantly, inquire how often and in what manner the patient washes. In the physical examination, look for evidence of sinus tract formation--extending, tunneling lesions with openings to the surface. Use Wood's light examination for the density of follicular fluorescence to rule out failure to properly absorb an antibiotic; fluoresce the oral mucosa to rule out failure to comply when the antibiotic is a tetracycline. Culture the surface aerobic flora on routine media with and without the antibiotic in question to settle any question of malabsorption. A systematic approach to these possibilities will usually uncover the factor or factors responsible for therapeutic failure. Clinical improvement promptly follows, once proper measures are initiated to neutralize the aggravating forces.


Epidermabrasion for acne: the polyester fiber web sponge. Physical-mechanical exfoliation with the nonwoven polyester fiber web sponge is an effective adjunct to the treatment of comedonal and pustular acne. Precisely controlled epidermabrasion is achieved by varying pressure, velocity, duration and frequency of use. Side effects are negligible and patient acceptance is high. Effectiveness is not dependent upon erythema and scaling since the web sponge mechanically removes keratin excrescences and trapped hairs in pilosebaceous ducts.


Acne: treatment with minocycline.

Acne: treatment with minocycline. Forty-seven patients with acne, unresponsive to tetracycline and erythromycin, were treated with 100 mg minocycline daily. About one-quarter showed a 50% improvement or better. Five patients became dizzy during the first week of therapy, making it necessary to stop the medication in four instances. Two patients stopped treatment after several months because of esophagitis in one and headaches in another. Vestibular side effects are the most common complication of treatment. Patients should be warned about this side effect and if it occurs should avoid driving or handling machines. In some instances, dizziness may be so severe that the drug will have to be discontinued.


A comparison of betamethasone benzoate gel and betamethasone valerate cream. One hundred and twenty-one patients were treated in a double-blind fashion with .025% betamethasone benzoate gel and 0.1% betamethasone valerate cream. Results were not statistically significant, although 14 of 16 patients with psoriasis showed excellent results with betamethasone benzoate gel, as opposed to six of 14 patients given betamethasone valerate cream.


Minocycline therapy in acne vulgaris.

Minocycline therapy in acne vulgaris. A double-blind, random distribution study showed that a lower than recommended dose of minocycline--50 mg twice daily--was as effective as a dose of 250 mg twice daily of tetracycline for treatment of acne vulgaris in comparable patient groups, and that minocycline produced no vestibular side effects at the lower dosage. Like tetracycline, minocycline did not produce the phototoxicity associated with demeclocycline or the life-threatening colitis associated with clindamycin. Patients in this study did not develop a resistance either to minocycline or to tetracycline. Studies of the use of minocycline in patients who have developed tetracycline resistance and long-range studies of patients on the new lower dose of minocycline are now underway.


An allergist looks at urticaria.

An allergist looks at urticaria. Some etiologic possibilities which must be considered are foods, drugs, infection, inhalant sensitivity, psychic factors, physical agents, underlying connective tissue disease or neoplasm, insect bite or stings and genetic abnormalities. A painstaking history and a complete physical examination are, of course, mandatory. These are followed by appropriate studies for whatever etiologic factors are suggested by the history and physical examination. Certain routine or more sophisticated studies might be indicated including a complete blood count, urinalysis, stools for ova and parasites, antinuclear antibody titer, complete complement, sedimentation rate, sinus, chest and dental X rays and any other specified test depending on where the clues lead. O'Loughlin described a practical approach in the use of laboratory studies for the diagnosis of chronic urticaria. Skin tests can be helpful especially for inhalants, but food tests are usually not reliable in the diagnosis of chronic urticaria. The acute urticaria reaction to a food is clinically obvious and this type of patient does not usually seek medical attention or need extensive investigation. Treatment includes a few basic medications. Hydroxyzine (Atarax, Vistaril), which combines tranquilizer and antihistamine action, is frequently effective. Cyproheptadine HCL (Periactin) both a serotonin and histamine antagonist with anticholinergic effect, is also helpful--especially in combination with hydroxyzine. Antihistamines, ephedrine, epinephrine, aminophyllin and occasionally corticosteroids are helpful. Immunotherapy with inhalants is occasionally indicated. Eliminating possible offending foods, dyes or drugs has been previously discussed. Anti-candidal therapy and low yeast diet is effective when indicated. The final aspect of the investigation and treatment process might best be described as "patient support"--patience on the part of the physician. It should be realized that in 75% of the cases of chronic urticaria, no convincing etiology is found. It should also be realized that urticaria all too frequently "settles down" due as much to the natural course as to the careful ministrations of the physician.


The pathogenesis of the comedo.

The pathogenesis of the comedo. The pathogenesis of acne is briefly reviewed and photographic evidence related to the production of follicular plugging is presented. One simple method of demonstrating this plugging for experimental use is described. Although juvenile acne is a benign, self-limited disease, it is extremely common and sometimes devastating. It is hoped that this presentation will lead to better understanding of its management.


"Witch doctor?" A hexing case of dermatitis. A Mexican-American woman presented with exfoliative dermatitis complicated by a "curse". She was cured by a combination of bland topical therapy and casting off of the spell by a curandero.


Acne treatment: a comparative efficacy trial of clindamycin and tetracycline. Tetracycline was compared to clindamycin as adjunctive therapy in the treatment of moderate to moderately severe acne under double-blind controlled conditions. Both antibiotics were efficacious and differences were not appreciable. Lesion counts of both comedones and pustules were reduced and clinical improvement was noted in the majority of subjects. Side effects were not a problem. The place of clindamycin in the therapeutic armamentarium of the dermatologist is discussed.


Dermatologic hazards from ethylene oxide. The more recent application of ethylene oxide as a gas sterilizing agent for medical supplies has introduced new problems for this old chemical. Not only is ethylene oxide a potent skin irritant but also delayed hypersensitivity and immediate hypersensitivity have been reported, In this article, chemical properties of this agent and sources of industrial exposure are discussed, and the literature regarding ethylene oxide dermatitis is reviewed.


The effect of Sch 1000 and disodium cromoglycate on exercise-induced asthma. The effect of disodium cromoglycate and Sch 1000 on exercise-induced asthma was studied in nine patients. The exercise stimulus consisted of either treadmill running or jogging; spirometric measurements were made before and at intervals after exercise. In six patients, disodium cromoglycate and Sch 1000 were both effective in preventing exercise-induced asthma. In two patients, Sch 1000 was effective, while disodium cromoglycate gave no protection. In the remaining patient, disodium cromoglycate was more effective than Sch 1000. The findings of this study suggest that the mechanism of exercise-induced asthma may be multifactorial, and the relative importance of each factor may vary in different patients.


Bronchodilator action of the anticholinergic drug, ipratropium bromide (Sch 1000), as an aerosol in chronic bronchitis and asthma. Ipratropium bromide (also known as Sch 1000) is a new atropine-like bronchodilator drug whose mechanism of action is via an anticholinergic pathway and may decrease cyclic guanosine monophosphate. Although of established efficacy in asthma, there are no studies of the use of ipratropium in patients with chronic bronchitis. The single metered aerosol doses of 10 mug, 20 mug, 40 mug and 80 mug of ipratropium bromide, 75 mug and 150 mug of isoproterenol, and placebo were studied in 20 adult patients, half with asthma and half with chronic bronchitis. To qualify, all patients demonstrated at least 20% improvement in the forced expiratory volume in one second while in the drug-free state when tested with isoproterenol. All subjects were tested for six hours with each agent in a double-blind crossover design. The dose-response aspects of the study indicate that in bronchial asthma the optimal range of dosage is 40 mug to 80 mug of ipratropium bromide. These doses are superior to isoproterenol in duration of action. In chronic bronchitis, all doses of ipratropium showed prolonged efficacy, but 80 mug was superior. Isoproterenol lacked this sustained efficacy. No significant alteration in pulse or blood pressure was observed. Ipratropium appears to be an important addition to the bronchodilator agents used in isoproterenol-responsive obstructive pulmonary disease.


Exercising pulmonary blood flow in mitral stenosis with anomalous pulmonary venous connection. Exercising pulmonary blood flow was estimated from indicator-dilution curves in a patient with the infrequent combination of rheumatic mitral stenosis and anomalous pulmonary venous connection from the left lung. During supine exercise against progressively increasing external workloads, the proportion of flow to each lung remained nearly constant. The pulmonary vascular resistance was highest in the left lung, which emptied into the low-pressure systemic vein. Although right and left atrial pressures differed markedly during supine exercise, the proportion of pulmonary blood flow shunted to the systemic venous sytem remained essentially unchanged.


Thrombosed giant left atrium mimicking a mediastinal tumor. A patient with rheumatic heart disease, mitral stenosis, and mitral insufficiency is described. The thrombosed giant left atrium paralyzed the left vocal cord and completely obstructed the bronchi to the middle and lower lobes of the right lung. The giant left atrium mimicked a mediastinal tumor on the chest x-ray film.


Replication of chromosomal DNA in diploid Drosophila melanogaster cells cultured in vitro. Replication rate and replicon sizes in chromosomal DNA of in vitro cultured diploid D. melanogaster cells were determined using autoradiography of 3H-thymidine labeled DNA. Synthesis of DNA in euchromatic and heterochromatic regions of Drosophila diploid cells occurs at different periods of the S phase which last 10 h. During the first 4 h the synthesis is observed only in euchromatic regions. The heterochromatic synthesis starts shortly before the synthesis in euchromatic regions is completed and lasts for 6 h until the end of the S phase. The cells were synchronized by 5-fluorodeoxyuridine which blocked the diploid cell DNA synthesis. Synthesis was found to start simultaneously in most euchromatic replicons. In the majority of the replicons the synthesis started at a single point and proceeded bidirectionally. The average rate of DNA synthesis per fork was 12.5 mum/h (38kb). The mean distance between the middle points of adjacent labeled regions was 70 mgm (210 kb). The size of most replicons ranged from 40 to 120 mum. - These estimates do not apply to the heterochromatic portions of the D. melanogaster genome since the measurements have been carried out on DNA preparations obtained during the first 2 h of the S phase. - On the average, a replicon can consist of 7 chromomeres since the size of a replicon in diploid cell chromosomal DNA and DNA length of a polytene chromomere average 210 and 30 kb, respectively.


Central serotonergic mechanisms and development of morphine dependence. The effects of different manipulations of brain serotonin (5-HT) content on the development of morphine dependence were investigated in rats, which were implanted with morphine pellets for 40 days. Serotonin content was decreased by (a) short or long term inhibition of tryptophan hydroxylase with para-chlorophenylalanine (PCPA), (b) by short or long term degeneration of 5-HT containing nerve terminals with 5,6-dihydroxytryptamine or (c) by degeneration of 5-HT containing nerve terminals by lesioning of midbrain raphe nuclei. With all methods used, the frequency of withdrawal jumping was significantly reduced, while other withdrawal signs remained more or less unchanged. Additional administration of 5-HTP to chronically PCPA treated rats did not reverse the PCPA effect. Since chronic reduction of 5-HT level during the whole time of morphine exposure changed withdrawal symptomatology in nearly the same way as did a decrease in 5-HT  level during the time of withdrawal only, it is suggested that serotonergic mechanisms are not linked to the basic processes underlying dependence development but that they are only involved in the nervous pathways mediating the expression of some withdrawal signs.


[Sex hormones and depth of voice in the male (author's transl)]. Correlations between sex hormone levels and the male depth of voice were investigated in 102 singers. As compared to tenor singers higher testosterone and lower oestradiol plasma concentrations were measured in bass and baritone singers. This resulted in higher testosterone/oestradiol ratios due to increased androgens in those with deeper voices. Deeper voices were associated with taller and heavier body build. In the young age group sexual activity was highest among the bass voices, in the middle and old age group tenors were most active. There were no depth of voice-related differences as regards the sequence and occurrence of different pubertal characteristics. Only future bass singers had an increased of acne. The results indicate that the different depths of the male voice are influenced by different concentrations of circulating sex hormones and also by the androgen sensitivity of the target organs.


[The "expert-killer" syndrome (author's transl)]. The "expert-killer" syndrome observed in 20 patients is a narcissistic subdivision which can be separated from the other organic neuroses. Clinically it is characterised by the triad: a) diffuse pain with numerous investigations and operations, b) absence of a diagnosis and adequate treatment, c) pathological doctor-patient relationship. The disease is based on indefinite and functional pains in the abdomen, neck and back. The failure to classify it with a clinically defined somatic disease leads to multiple diagnostic attempts which become more aggressive with increasing lack of success. Multiple operations occur in all the histories. The doctor-patient relationship is characterised by an initial idealisation of the doctor which quickly turns to rejection on account of his limited abilities. The patient only tolerates a short contact with the doctor. In the personality narcissistic traits and the persistence of an external ideal are apparent. The syndrome occurs in life at the point when the idealised partner disappoints the patient. These trigger factors are to be considered as a narcissistic insult. The functional pains are an attempt to restore the threatened self of the patient. The treatment consists of psychotherapy.


Effects of Solanum malacoxylon on duodenal calcium binding protein in the diabetic rat. Duodenal calcium absorption and calcium binding protein (CaBP) are depressed in uncontrolled experimental (alloxan and streptozotocin) diabeties in the rat. Administration of an aqueous extract of the South American plant Solanum malacoxylon to diabetic rats restores duodenal calcium absorption to control levels. Since CaBP is thought to play a role in intestinal calcium transport, we isolated CaBP from duodenal mucosa of control, diabetic, and S. malacoxylon-treated diabetic rats. CaBP, whose concentration is about half normal in mucosal extracts from diabetic rats by treatment of diabetics with Smalacoxylon extracts. Hence these studies provide a further correlation between duodenal calcium absorption and levels of duodenal CaBP. In addition, a new purification procedure is described which produces a 17-fold increase in purity of CaBP above that attainable by our previously reported method.


Serotonin mediated inhibition of episodic luteinizing hormone release during electrical stimulation of the arcuate nucleus in ovariectomized rats. The possible involvement of serotonin (5HT) in mediating the inhibition of episodic LH release produced by electrical stimulation of the arcuate nucleus (ARH) of ovariectomized rats was investigated. Animals were pretreated with p-chlorophenylalanine (PCPA) an inhibitor of 5HT synthesis, or PCPA and 5-hydroxytryptophan (5HTP). Unanesthetized, unrestrained rats were bled continuously through indwelling cannulae prior to the onset of stimulation, and bleeding continued for 3 h during which electrical stimulation was applied for one or two 60 min periods separated by a 60 min nonstimulation period. Whole blood was analyzed for LH by radioimmunoassay. Brain 5HT levels were determined in individual rats by a fluorometric method. PCPA caused a significant depletion in brain 5HT levels by 71h. Administration of 30 or 120 mg/kg 5HTP to PCPA treated rats resulted, respectively, either in a restoration of normal brain 5HT levels, or a 3 1/2-fold increase above controls. Although stimulation of the ARH inhibits episodic LH release in ovariectomized rats, following depletion of brain 5HT levels with PCPA stimulation of the ARH markedly increased LH release. This increase lasted for most if not all of the stimulation period and was followed by a 1 h period of little or no LH secretion. These increases were not seen during stimulation in other hypothalamic areas outside the ARH. Reestablishment of normal, or even further increasing, brain 5HT levels in PCPA treated rats with 5HTP greatly reduced the extent of the increase in LH release seen during ARH stimulation, but only restored inhibition of LH secretion in a few animals. However, a decrease in LH rt 1) a decrease in brain 5HT levels reverses the effect of ARH stimulation on LH release from inhibition to excitation, and 2) repletion of 5HT levels greatly reduces the magnitude of this increased LH release. These data suggest that 5HT  may be involved in mediating the inhibition of episodic LH secretion by electrical stimulation of the ARH. The inability of 5HTP to restore completely inhibition of episodic LH release during ARH stimulation suggests that a substance other than 5-HT may also be involved in mediating this response.


Enzyme activities in human endometrium, myometrium and leiomyomas of the uterus. Certain selected enzymes of carbohydrate metabolism were measured in samples of endometrium and myometrium from women who were premenopausal or postmenopausal. In addition, a number of samples of leiomyoma were obtained and assayed. Activities of several enzymes were higher in endometrium from premenopausal women compared to those in postmenopausal women; activities in myometrium were similar regardless of menopausal status. The activities of G6PD, ICD and GPI appeared to be lower in leiomyoma samples versus myometrial samples from premenopausal women; however, these differences were not apparent when enzyme activity was expressed per milligram protein.


Mucidin resistance in yeast. Isolation, characterization and genetic analysis of nuclear and mitochondrial mucidin-resistant mutants of Saccharomyces cerevisiae. Mutants of Saccharomyces cerevisiae resistant to the antibiotic mucidin, a specific inhibitor of electron transport between cytochrome b and c, were isolated and divided into three phenotypic groups, as follows. Class 1 mutants were cross-resistant to a variety of mitochondrial inhibitors and exhibited no resistance at the mitochondrial level. Class 2 mutants were specifically resistant to mucidin exhibiting resistance also at the level of isolated mitochondria. Biochemical studies indicated that the mucidin resistance in class 2 mutants involved a modification of mucidin binding of inhibitory sites on the mitochondrial inner membrane without a significance change in the sensitivity of mitochondrial oxygen uptake to antimycin A, 2-heptyl-4-hydroxyquinoline-N-oxide, and 2,3-dimercaptopropanol. Class 3 was represented by a mutant which showed a high degree of resistance to mucidin and was cross-resistant to a variety of mitochondrial inhibitors at the cellular level but exhibited only a resistance to mucidin at the mitochondrial level. Genetic analysis of mucidin-resistant mutants revealed the presence of both nuclear and mitochondrial genes determining mucidin resistance/sensitivity in yeast. Resistance to mucidin in class 1 mutants was due to a single-gene nuclear recessive mutation (mucPR) whereas that in class 2 mutants was caused by mutations of mitochondrial genes. Resistance in class 3 mutant was determined both by single-gene nuclear and mitochondrial mutations. In the mitochondrial mutants the mucidin resistance segregated mitotically and the resistance determinant was lost upon induction of petite mutation by ethidium bromide. Allelism tests indicated that the mucidin resistance mutations fell into two genetic loci (MUC1 and MUC2) which were apparently not closely linked in the mitochondrial genome. Recombination studies showed that the two mitochondrial mucidin loci were not allelic with other mitochondrial loci RIB1, RIB2 and OLI1. An extremely high mucidin resistance at the cellular level was shown to arise from synergistic interaction of the nuclear gene mucPR and the mitochondrial mucidin-resistance gene (MR) in a cell. The results suggest that at least two mitochondrial gene products, responsible for mucidin resistance/sensitivity in yeast, take part in the formation of the cytochrome bc1 region of the mitochondrial respiratory chain.


Early biochemical disorders in hindlimb muscles following femoral artery stenosis in dogs: oxidative metabolism. An approach to explain the early metabolic disturbances induced by a moderate ischaemia on the basis of comparative  biochemical investigations concerning the oxidative metabolism in the skeletal muscles, is the object of the present paper. These investigations have revealed the following findings: (i) during a slight ischaemia the skeletal muscle maintains its ability to oxidize in vitro lactate and exhibits an increased activity in oxidizing pyruvate, succinate and L-glutamate, and (ii) the stores of adenosine and ATP are depleted and an important accumulation of inorganic phosphate, accompanied by a remarkable activation of phosphatases, occurs in the ischaemic muscle, while no significant changes in the ATPase and creatine phosphokinase activities and in the amount of AMP, ADP and creatine phosphate are detectable in this muscle.


Resection of the abdominal wall in metastasis from cancer of the bladder, kidney or colon. Metastases in the abdominal wound occur in about 1% of a material of bladder tumors and less frequently in renal or colon carcinoma. They are sometimes accompanied by metastases elsewhere. Even if the abdominal wall metastases are very large, extensive resection of all layers of the wall may enable the patient to survive for more than 5 years. Free skin grafts are sometimes sufficient to cover the defect. There is no herniation and no impairment of respiration. Metastases in the vicinity of a colostomy or ileostomy may necessitate an operation. Radiation does not appear to provide any relief.


Isolated ventricular inversion with double inlet left ventricle. 2 patients with viscero-atrial situs solitus, isolated ventricular inversion (IVI) and double inlet right-sided morphologic left ventricle are presented. Isolated ventricular inversion is a rare cardiac anomaly characterized by ventricular inversion, subpulmonary conus, and ventriculo-arterial concordance. Their angiocardiographic and pathologic features are presented, and the morphologic findings of the 9 patients in the literature with isolated ventricular inversion are reviewed. Of the 11 known patients with isolated ventricular inversion, levocardia was present in 10 and dextrocardia in 1; viscero-atrial situs solitus in 9 and inversus in 2; L-ventricular loop in 9 and D-loop in 2. The atrial septum was intact in 4. An intact ventricular septum was noted in only 2 patients while in 3, more than one ventricular septal defects were present, and 2 patients exhibited morphologic single ventricle. A solitary ventricular septal defect was noted in the remainder. Significant tricuspid valve abnormalities, including atresia, stenosis or hypoplasia with supravalvular fibrous ring were found in 7 patients. In 2 of these, both with significant obstruction at the tricuspid valve, both atrioventricular valves emptied into the morphologic left ventricle--thus isolated ventricular inversion with double inlet left ventricle. Pulmonary outflow tract obstruction was evident in only 3 patients. Total anomalous pulmonary venous return occurred twice and right juxtaposition of the atrial appendages once. Thus, while the patient with isolated ventricular iversion may present with clinical and hemodynamic features characteristic of classical transposition physiology the high frequency of significant associated anomalies would complicate this. Finally, the anomaly must be differentiated from the levo-transposition, isolated atrial inversion, and the anatomically corrected malpositions.


A latex agglutination test for rapid quantitative estimation of the plasmin-antipalsmin complex in human plasma. An antiserum was raised in rabbits against human plasmin-antiplasmin complex and rendered specific for neoantigens of this complex by absorption with purified plasminogen and plasma. Polystyrene particles were coated with the specific antibodies and used in an agglutination test for the determination of plasmin-antiplasmin complex in the plasma from various patients. Purified plasmin-antiplasma complex at a concentration of 0.1-0.2 mg/l was found to cause a clear agglutination of the particles. Activation of fresh human plasma with urokinase caused progressive generation of agglutinating activity up to a plasma dilution of 1/480. Intravenous infusion of streptokinase into patients resulted in an increase of the plasmin-antiplasmin titre of at least 1/240. Sera from patients with rheumatoid factor also agglutinated the particles but this activity could be removed by absorbing rheumatoid factor on insolubilized human IgG. Out of 101 male and twenty-three female control subjects, only three men had a plasmin-antiplasmin titre above 1/16. Of 230 hospitalized patients, plasmin-antiplasmin titres of 1/40 or more were detected in twenty-five patients. Most of these patients had diseases which are frequently associated with in vivo coagulation or fibrinolysis, but among them there was only one who showed diffuse intravascular coagulation detectable by classical methods. In the absence of an increased plasmin-antiplasmin titre none of the haemostasis analyses were indicative of in vivo coagulation or fibrinolysis. Seven out of eight patients with diffuse intravascular coagulation of various origin had plasmin-antiplasmin titres of 1/80 or 1/160. Thus, the present latex agglutination test, owing to its simplicity and sensitivity, appears to be a practical routine screening test for detecting fibrinolytic activation in plasma.


Effect of quipazine, a serotonin-like drug, on striatal cholinergic interneurones. Quipazine (30 mg/kg i.p., 60 min), a serotonin-like drug increased ACh levels in the striatum (37%) but was without effect on the transmitter content in the hippocampus and the parietal cortex of the rat. Added in vitro(10(-5) M) or injected in vivo, quipazine did not affect choline acetylase and cholinesterase activities in striatal tissue. The drug effect on striatal ACh levels did not appear to be related to an interaction with dopamine metabolism. Indeed quipazine still increased striatal ACh levels after degeneration of the dopaminergic neurons had been induced by local injection of 6-OH-DA. p-Chlorophenylalanine (PCPA) pretreatment (300 mg/kg, 48 and 24 h before the experiment) definitely prevented the quipazine effect on ACh levels. This result suggested that the drug may partially act by its interference with 5-HT metabolism. 5-Methoxy-N,N-dimethyltryptamine (10 mg/kg, i.p., 30 min), a serotonergic agonist, induced a weak but significant increase in ACh levels. These data provide some preliminary evidence for the existence of an inhibitory control of the cholinergic interneurones by the serotonergic neurones projecting to the striatum. However, the lack of effect of 5-hydroxytryptophan (100 mg/kg i.p.), PCPA (2 x 300 mg/kg i.p.) and of Lilly 110 140 (10 mg/kg i.p.) and chlorimipramine (10 mg/kg i.p.), two potent inhibitors of 5-HT uptake, on striatal ACh levels indicate that further experiments are required to retain this hypothesis.


[Effect of parathyroid hormone on electrical and contractile processes in myocardial cells]. In normal ionic milieau, the parathyroid hormone (PTH) generated a biphasic effect: the initial increase in amplitude and duration of A at the plateau level, and the following decrease in amplitude and duration of AP of the myocardial cells at every level of repolarization. The contractile activity steadily decreased under the PTH effect. The negative inotropic effect of the PTH in its quantitative and temporal aspects was diminished by a preliminary administration of calcitonin. The PTH effect is supposed to be based on an increase in the calcium flow through slow CaNa channels and on Ca binding in intracellular sites of storage.


[A radioimmunoassay method for simultaneous determination of pregnenolone, pregnenolone sulfate, dehydroepiandrosterone and dehydroepiandrosterone sulfate in human plasma (author's transl)]. A radioimmunoassay method has been developed for the simultaneous determination of pregnenolone, pregnenolone sulfate, dehydroepiandrosterone(DHA) and dehydroepiandrosterone sulfate (DHA sulfate). The method consists of the following procedures: 1) ether extraction of unconjugated compounds, 2) extraction of sulfates fromaqueous residue with ethyl acetate, 3) solvolysis with sulfuric acid at 40 degree C for 60 minutes, 4) celite column chromatography to separate individual compounds, 5) radioimmunoassay. Efficiencies of solvolysis for pregnenolone sulfate and DHA sulfate are 94 and 80%, Precision and accuracy studies have shown that the assays of sulfates as well as unconjugates are reproducible and accurate. Specificity was ascertained by parallelism and linearity studies. No interfering substance was detected in appreciable quantity. Plasma levels of these four compounds were determined in specimens obtained from 15 normally ovulating women. To represent the whole menstrual cycle, samples were taken 8 days before LH peak (LH-8), the day of LH peak (LH = O) and 8 days after LG peak (LH+8). Plasma contents of these compounds (geometric mean in ng/ml and 95% confidence limits in parentheses) are as follows: pregnenolone, LH-8: 1.33 (1.02-1.74), LH = 0: 1.45 (1.22-1.72), LH+8: 1.88(1.70-2.21); pregnenolone sulfate, LH-8: 70.0 (55.9-89.2), LH = 0 57.5 (40.0-82.7), LH+8: 102 (81.5-129); DHA, LH-8: 5.38 (3.90-7.43), LH = 0: 4.90 (3.58-6.79), LH+8: 4.58 (3.12-6.83), DHA sulfate, LH-8: 1480 (1110-1980), LH = 0: 1570 (1150-2140), LH+8: 1590 (1150-2190). Both pregnenolone and pregnenolone sulfate levels of 8 days after LH peak are significantly higher than those of other two days. Conversely, plasma DHA and DHA sulfate levels fluctuate over wide range with no consistent trend.


[The effect of various amines on TRH contents in rat brain (author's transl)]. To study the effect of vatious amines on TRH contents in rat brain, various amines or inhibitor of synthesis of amines were injected into rat through i.v. or i.p.. Rats were decapitated and brain was frozen in dry ice and aceton. TRH contents in hypothalamus(H), cerebrum(C) and cerebellum and brain stem (C and S) were measured by TRH radioimmunoassay. TRH contents in normal rats were 3.9+/-0.5ng in H, 2.6+/-0.5NG IN C and 1.6+/-0.3ng in C and S. TRH contents in all parts of brain were increased in L-DOPA treated group and did not change in T3 or T4 treated group. TRH contents in all parts of brain were decreased in alpha-methyl-DOPA, alpha-methyl-para-tyrosine, fusaric acid and 5-HTP treated groups. In D,L-p-chlorophenylalanine treated group TRH contents in brain were increased only in hypothalamus. In L-DOPA or 5-HTP treated group with T4 or T3 preadministration, TRH contents in all parts of brain were same levels of L-DOPA or 5-HTP treated group. The above data suggested the TRH contents in rat brain were increased with increase of dopamine level in rat brain and decreased with increase of serotonine level or decrease of noradrenaline level in rat brain and inhibitory effect of T4 or T3 on TRH release might be mediated through dopaminergic and serotonergic mechanism.


Treatment of acne vulgaris with the retinoic acid derivative Ro 11-1430. A controlled clinical trial against retinoic acid. In a double-blind, randomized, group-comparative clinical trial, 31 patients with acne vulgaris received topical treatment for 6-8 weeks with a lotion containing either 0.05% retinoic acid or 0.1% of the retinoic acid derivative Ro 11-1430. The side-effects erythema, desquamation and burning were significantly less frequent with Ro 11-1430 than with retinoic acid. The treatments appeared to be approximately equally effective in reducing the number of acne elements, but due to the limited number of patients studied, the trial was admittedly not sufficient to detect differences with regard to therapeutic efficacy.


Temetex in the treatment of steroid-responsive dermatoses. Five hundred and seventy-five patients with various steroid-responsive dermatoses were studied for up to six weeks in eighty-eight separate general practices using a new topical corticosteroid. Temetex (diflucortolone valerate 0-1%). It was concluded that Temetex is both effective and well tolerated in a wide variety of conditions, especially eczema and psoriasis. It was also shown that a large-scale general practice trial can be carried out efficiently with a very high compliance rate.


Lack of thyroid hormone effect on activation energy of NaK-ATPase. In order to differentiate whether activation of NaK-ATPase in thyroid thermogenesis is due to increased numbers of active 'sodium pump' units or due to a change in the kinetics of the enzyme, the effect of T3 on activation energy (Ea) of NaK-ATPase was determined in rat liver, kidney and brain. Injection of T3 produced significant increases in the specific activity of NaK-ATPase in liver and kidney but not in brain homogenates. T3 injections produced no significant change in the Ea of NaK-ATPase in any of the three tissues. The data are compatible with the hypothesis that thyroid stimulation of the sodium pump is brought about by an increase in the number of active pump units.


Should ECG criteria be modified for geriatric patients? When an elderly patient has an abnormal electrocardiogram but no other objective evidence of heart disease, the physician may question whether the ECG is really a reliable index of heart disease in old people or whether aging has some influence on which findings are normal and which are abnormal. The study reported here plus data gathered from an extensive review of the literature indicate the ECG criteria do not have to be changed for geriatric patients. Regardless of age, the prognosis of a specific abnormality remains that of the underlying disease. With age, both heart disease and abnormal electrocardiograms increase in incidence--in a parallel fashion. Specific abnormalities that increase in frequency are first-degree atrioventricular block, bundle-branch block, ST-T wave changes, premature systoles, left anterior hemiblock, left ventricular hypertrophy, and atrial fibrillation. Those that correlate strongly with heart disease are atrial fibrillation, left bundle-branch block, and nonspecific intraventicular condution defect.


The ECG in old age: implications for diagnosis, therapy, and prognosis. The electrocardiogram is a valuable aid in diagnosing and treating heart disease in the elderly and in determining the prognois. In general, mortality is lower in old persons with ECG abnormalities than in younger ones, and some changes are not considered abnormal. P wave notching, slurring, and loss of amplitude are too common to be of diagnostic significance, and T wave inversions and S-T segment depressions have too many causes to be specific. A persistently prolonged P-R interval often is associated with recurrent atrial arrhythmias, junctional rhythms, and conduction distrubances. A short interval, on the other hand, may be noted for a long time without paroxysmal atrial tachycardias. Degenerative and ischemic changes in the conduction system result in a variety of arrhythmias and conduction disturbances. The classic sick sinus syndrome is not seen as often as the incomplete forms, such as sinus bradycardia with atrial premature contractions. With the exception of left inferior hemiblock, bundle-branch blocks are common. Similarly, ventricular and atrial premature contractions increase with age. ECGs taken routinely over a period of years help differntiate ventricular from supraventricular tachycardias with aberrant conduction.


Changes in the erythrocyte sodium pump with age. Various estimations of the erythrocyte sodium pump were determined in 18 female and 11 male adult subjects. In the female group, but not in the male group, the sodium concentration increased with age; the erythrocyte active transport decreased and passive transport increased with age and could account for the observed change in erythrocyte sodium concentration with age. The erythrocyte Na-K ATPase decreased with age in the females and this could account for the observed change in active transport.


[Radiological examination in Goodpasture's syndrome (author's transl)]. Functional renal scans proved to be useful in assessing changes in renal function (progression and regression) in a patient with Goodpasture's syndrome. Perfusion lung scintigraphy revealed extensive, but circumscribed, areas of reduced activity. This scintigraphic phenomenon indicates reduced capillary perfusion in the lungs, paralleling the appearance of the radiograph.


[Lung function scintigraphy in the diagnosis of regional disturbances of ventilation (author's transl)]. Lung function scintigraphy is the method of choice for the diagnosis of regional ventilation disturbances. The aim of this study was to determine which of various parameters is the most reliable. Sensitivity of the 3-minute retension test is 96%, of the single breath 45%, equilibration 32% and of the ventilation index, only 28%. Sensitivity of the various parameters for demonstrating multi-focal ventilation abnormalities is 100% for the 3 minute retention test, 32% for single breath, 19% for equilibration and 21% for the ventilation index. The underlying basis for these findings is discussed and it is concluded that it is possible to simplify the technique when dealing with regional ventilation abnormality in obstructive airway disease, but not when dealing with other restrictive changes.


[The radiological diagnosis of non-calculous biliary duct obstruction (author's transl)]. A diagnosis of obstructive biliary duct disease was achieved in 80% of 63 patients using endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous trans-jugular cholangiography (PTJC) alone or in combination, and taking account of the clinical features. In obstructions of themajor intrahepatic ducts and of the hepatic ducts (type I) a smooth occlusion indicated a carcinoma. Narrow forms of stenoses could not be differentiated, but with a history of previous operation, fibrous strictures were most likely. Obstructions at the point of confluence (type II) showed smooth narrowing if due to fibrous strictures, whereas carcinomas produced an irregular termination. Obstructions of the common bile ducts (type III) resembled those of type II. A smooth termination within the pancreas indicates a pancreatic carcinoma. Inflammatory disease in the head of the pancreas usually produces a tubular stenosis, while cysts of the pancreas result in smooth impressions and displacement.


[Megacaliosis--diagnosis and differential diagnosis (author's transl)]. Megacaliosis is a renal dysplasia which is characterised by rudimentary papillae. The pathogenesis, clinical features and radiological appearances in fire cases are described and the differential diagnosis from other types of calyceal ectasia is discussed, In typical cases the diagnosis of megacaliosis can be made from the excretion urogram. We regard divided renal function studies as essential before making the diagnosis. Where the renal changes are not quite typical, it is necessary to exclude obstructive and inflammatory disease, vesico-ureteric reflux and renal tuberculosis.


[Renal blood flow measurements by cine-angiodensitometry (author's transl)]. Angiodensitometry complements conventional renal angiography and provides important additional functional information without subjecting the patient to any further stress. Since blood flow through the renal arteries can be determined, it is an important method for the preoperative investigation of renal disease.


[Multiple occlusions and stenoses of the abdominal aortic branches with development of Riolan's collateral and hypertension (author's transl)]. One case of multiple occlusions and stenoses of the abdominal aortic archs with development of Riolan's collateral in a young patient with hypertension is described. In the literature some cases are pointet out, which clinically resemble our patient and where the aetiology is not clarified. -- In the discussion about the aetiology of this vascular anomaly a developmental anomaly and mechanical compression by the crura diaphragmatica are named. We think, that an unspecific arteriitis similar to the in Japan well known Tacaysau-Aortitis must also be discussed. This unspecific arteriitis of the abdominal aorta and its branches would explain the occlusion and stenosis of several arteries with development of Riolan's collateral and manifestation of hypertension.


[Flow abnormalities in the carotid due to trauma and their differential diagnosis (author's transl)]. Amongest nine cases of internal carotid artery thrombosis following blunt trauma, six showed a typical acute contrast termination several cm. beyond the carotid bifurcation. In the other cases, one was taken with an unusual projection, one had a high occlusion beyong the origin of the ophthalmic artery and the third showed a stenosis due to a mural thrombosis. Perforating carotid injuries should be examined angiographically because of the danger of late complications. Two functional occlusions were observed following acute vascular angulation. This type of occlusion is contrasted with the convex vascular margin in the internal carotid artery seen in atherosclerotic, embolic or "spontaneous" carotid occlusion.


[Scintigraphic demonstration of cerebral sinus thrombosis (author's transl)]. The scintigraphic findings due to sinus thrombosis are described; the condition was followed up and there was partial return to normal. The diagnostic value and indications of cerebral scintigraphy and cerebral angiography in cases of sinus and/or venous thrombosis are defined.


[Late meningeal changes due to water-soluble myelographic contrast medium (author's transl)]. Late meningeal changes due to various contrast media of the water-soluble type used for radiculography were analysed and the causes for the changes are discussed. The osmotic properties of the substance are an important aspect of the contrast medium. Hints for avoiding late complications are given.


[Bone and joint changes due to compressed air in divers and Caisson workers (author's transl)]. The radiological and morphological changes of Caisson disease in the skeleton are well known. The findings of interest to radiologists are described. Because of its position, its was possible to review a large number of divers in Kiel; these have been under observation for years, and even decades. The development, manifestation and course of chronic skeletal changes due to compressed air are described to compressed air are described and, according to severity, are classified into types 1 to 4. Late changes are discussed in detail, since these are of importance in relation to compensation.


[The quality of disturbed radiation to the ovaries during diagnostic x-ray exminations (author's transl)]. Dose measurements and analysis of disturbed spectra have shown that protection of the ovaries against disturbed radiation is worth while, although its effectiveness decreases with higher tube voltages. Increasing tube voltage increases disturbed radiation to the ovaries; the quality of the disturbed radiation is largely independent of the amount of filtration.


[Pulmonary perfusion in embolism of pulmonar arteries without pulmonary infarction (author's transl)]. Six autopsy lungs with embolism of the pulmonary arteries but without infarction, were subjected to comparative angiographic and morphologic examination of bronchial arteries. In pulmonary embolism without hemorrhagic infarction the disconnected vascular bed of pulmonary arteries can be demonstrated distally of the obstructive thrombo-embolism and with a noncapillary contrast medium. The vascular bed appears in intrapulmonal, precapillary, bronchopulmonal anastoses. The results of the investigation explain an intravital sufficient subsidiary circulation in the pulmonary areas separated from the normal circulation of pulmonary arteries. An extended subsidiary development of bronchial arteries in reaction to previous chronic pulmonary disease would help, according to our findings in postmortem lung angiographies, to support the circulation after embolism of pulmonary arteries.


[The radiology of the dorso-basal part of the chest (author's transl)]. The radiology of the dorso-basal part of the chest includes a number of unmistakable lesions with characteristic appearances. These are demonstrated by a series of appropriate cases (diaphragmatic processes, pulmonary sequestrations, pleural disease and the late effects of a pneumothorax). Their differential diagnosis is discussed.


[Radiological observations of the chest in progressive scleroderma (author's transl)]. All available chest radiographs of 50 patients with progressive scleroderma have been freshly evaluated. In 28 cases (56%), pulmonary involvement was diagnosed; its type and severity was classified according to the specimen films of the ILO-U/C 1971 classification for pneumoconiosis. Serial observations in 27 patients spanning a period of one to 21 years have shown that the course of the disease in the lung is unpredictable. Rapid progress of fibrosis is, however, uncommon. Two radiological appearances in the thorax, which are not specific, but are found predominantly in scleroderma are: 1 an air oesophagram on the lateral thorax film (8 cases) and erosions of the upper rib margins (5 cases). The importance of radiological examination lies in the fact that it confirms the clinical diagnosis and that it may indicate the cause of an otherwise undiagnosed pulmonary fibrosis.


[Alloplastic tracheal replacement].

[Alloplastic tracheal replacement]. 1. Replacement of the cervical trachea using Silasticprostheses was performed in sheeps with good long term results. 2. The superiority of subterminal suture cuffs is demonstrated. 3.A biological adhesive system supplementing the sutures of the anastomoses was highly effective. 4. The results of replacement of the canine tracheal carina are presented. 5. Since auto-, homo- and auto-alloplastic grafts do not epithelialize they are not capable of active secrection transport. Moreover they show a permanent tendency to shrink. We therefore conclude that the Silasticprosthesis is the best tracheal substitute available at this time for cases in which direct anastomosis is not feasible after segmental tracheal resection.


[Clinical experiences with terracortril ointment and cream]. The results of a clinical trial using a new preparation of Terracortril ointment and Terracortril cream without preservatives are reported. Apart from oxytetracycline 30 mg/g and 10 mg hydrocortisone alcohol/g, each drug contains polymyxin B 10,000 I.U./g. Of a total of 85 patients with primary and secondary pyodermias, 41 were completely or almost completely cured after application of ointment or cream respectively, 13 were largely, and 31 cases satisfactorily improved (see tables 1 and 2). The bacteriological findings are discussed. No skin irritations such as contact dermatitis were observed.


Neonatal effect of clomiphene and o,p'-DDT on hepatic oxidative metabolism of male rats. The hepatic oxidative metabolism of dehydroepiandrosterone (DHA) and aminopyrine has been investigated in adult rats of both sexes treated neonatally with either clomiphene citrate (100 mug on day 3) or o,p'-DDT (1 mg daily on days 2-3). The rates of 16 alpha-, 7 alpha- and 7 beta-hydroxylase activities of DHA and the N-demethylase activities of aminopyrine in hepatic microsomes of normal males were significantly (p less than 0.05) higher than those of females. Treatment with clomiphene citrate reduced significantly (p less than 0.05) the 16 alpha-hydroxylase activities of males and appeared to suppress the 7 alpha-hydroxylase and N-demethylase activities to a lesser extent. Neonatal o,p'-DDT also reduced these hepatic oxidative activities. Neither treatment affected the 7 beta-hydroxylase activities. On the other hand, no significant differences in these activities were observed between the control and the treated females, all of which had persistent vaginal estrus. Therefore, it appears that treatment of male neonates with these weak estrogenic compounds antagonizes the androgen-mediated expression of the DHA-16alpha-hydroxylase activity in liver.


Hormonal changes during puberty. IV. Longitudinal study of acrenal androgen secretions. Longitudinal studies of plasma dehydroepiandrosterone sulfate (DHEA-S) and dehydroepiandrosterone (DHEA) were made in 13 girls aged 7 years and 14 aged 10 years, during 3 years, at 6-month intervals. Similarly, two groups of 12 boys aged 8 years and 11 years were followed. In addition, 3 girls with premature adrenarche and 4 male patients with Addison's disease were studied. In the normal girls a significant rise of plasma DHEA-S and DHEA occurred from 6 years of bone age (51.4 +/- 9.0 ng/ml and 50.5 +/-9.2 ng/100 ml, respectively) to 8 years (119. 7 +/- 19.1 ng/ml and 94.5 +/- 16.5 ng/100 ml). A further significant rise was apparent at 11 years (385.8 +/-60.9 ng/ml) and 329.0 +/- 78.4 ng/100 ml). In boys, a similar rise of DHEA-S and DHEA was observed between 6 years of bone age (75.8 %/- 12 ng/ml and 44.3 +/- 7.6 ng/100 ml) and 8 years (157.4 +/- 28.9 ng/ml and 76.1 +/- 8.9 ng/100 ml). Furhter significant rise of DHEA-S and DHEA were seen at 13 years of bone age (563.7 +/- 123.7 ng/ml and 267.9 +/- 50.0 ng/100 ml, respectively). Testosterone in both sexes rose 2-3 years later than DHEA-S and DHEA. In female patients with premature adrenarche, higher plasma levels of DHEA-S and DHEA were found when compared to normal levels at similar chronological and bone ages. Very low plasma concentrations of DHEA-S and DHEA were obsrved in the patients with Addison's disease.


Psotcardiotomy syndrome: pathogenesis and management. It now appears probable that this syndrome and postinfarction syndrome result from an exaggerated immune response to cardiac damage. Both are self-limited, except following coronary artery bypass surgery, in which the incidence of graft occlusion may be high. Early recognition is vital so that treatment, with corticosteroids and aspirin, can prevent morbidity, anxiety, and inappropriate therapy.


Clinical experience with loop nephrostomy. The authors advocate the use of the U-nephrostomy as the routine measure in operative treatment of infected renal stones.


A prophylactic trial of iron and folic acid supplements in pregnant Burmese women. Hemoglobin (Hb) concentration, serum iron level, iron binding capacity and blood folate (Lactobacillus casei) activity were determined in 310 unselected pregnant Burmese women. Hb concentration was less than 11 g/dl in 72% of the women; the serum iron level was less than 50 mug/dl in 33%; serum folate activity was less than 3ng/ml in 13%; and red cell folate activity was less than 100 ng/ml in 17% of the women. Ninety-six of the women in our study were randomly divided into four groups, treated from the 22nd to the 25th week of pregnancy until full term with either ferrous sulfate containing 60 mg elemental iron twice daily, 5 mg folic acid twice daily, a combination of both, or a placebo only. At full term, Hb concentration fell in the groups given placebo or folic acid. On the other hand, in the groups given iron alone or iron plus folic acid there was an increase in Hb of 0.4 and 0.7 g/dl, respectively (intergroup difference not statistically significant). Serum iron and blood folate levels fell in the groups not receiving the appropriate hematinic. In spite of deficient serum and red cell folate levels in 30 and 40%, respectively, of the group on iron alone, the mean Hb concentration increased at full term and none of the women had a Hb concentration lower than 10 g/dl. Blood folate levels were lower in the iron-supplemented group than in the placebo group, indicating that iron deficiency does not aggravate the folate nutritional status.


[Pecilocin allergy].

[Pecilocin allergy]. In 1975 there were a total of 44 patients in the author's practice with a history of treatment with pecilocinum (Variotin). These patients were patch tested with pecilocinum, and seven were found to be allergic to this drug. In three of them the skin disease had been caused or exacerbated by pecilocinum. In the other four patients the allergy to pecilocinum must be regarded as an "immunological scar".


Lung mast cell density and distribution in chronically hypoxic animals. Changes in the density and distribution of pulmonary mast cells were determined in six mammalian species exposed to hypobaric hypoxia (PB = 435 Torr) for 19-48 days. Control animals were studied at 1,600 m (PB = 635 Torr). Total lung mast cell hyperplasia was observed only in calves exposed to high altitude. Pigs, rats, and sheep exhibited small, but insignificant, increases in mast cell density. Perivascular mast cell proliferation adjacent to vessels of 30-500 mum in diameter was seen in both calves and pigs. Bronchial, alveolar septal, and systemic tissue (tongue) mast cell hyperplasia was not observed in any of the species. Three indices of pulmonary hypertension (right ventricular hypertrophy, medial thickness of pulmonary arteries, and pulmonary arterial pressure) correlated with perivascular mast cell density. The findings indicate that perivascular mast cell proliferation may relate more to the morphological pulmonary vascular changes and to pulmonary hypertension than to hypoxia, leading to the speculation that mast cells increase in number in response to the hypertension, rather than to mediate and maintain the hypertension.


Hepatic excretion of cholecystopaques introduced into the canine jejunum. The biliary excretion of five oral cholecystopaques was measured following their introduction into the jejunum of bile fistula dogs. The mean maximal iodine concentration in the bile ranged form a low of 2.2 +/- 0.55 mg per ml following a dose of 33 mg of iodine per kg of iopanoic acid to a high of 12.9 +/- 1.4 mg per ml after the same dose of sodium ipodate. Cumulative excretion at the end of three hours was over five times greater with sodium ipodate in comparison to ipoanoic acid. It is felt that the best explanation of this date is the ability of the more water soluble media to pass through the unstirred water layer of the intestine.


Time course adaptations in cardiac and skeletal muscle to different running programs. The effects of chronic "steady-state" and high-speed interval running were investigated on time-course changes in certain biochemical properties of cardiac and skeletal muscle fiber types of rats. Nine weeks of the interval program resulted in significant increased (15%) in both cardiac enlargement and ATPase activity of myofibrils; whereas increases in these parameters were only transient and not significant at the termination of the program involving steady-state running. Neither program induced appreciable alterations in citrate synthase and phosphofructokinase activity in cardiac muscle. In fast-twitch white fibers, "steady-state" training induced only a transient 45% increase in citrate synthase activity in contrast to a progressive twofold change with interval training. Both programs resulted in similar increases (45-50%) in citrate synthase activity in fast-twitch and slow-twitch red fibers. However, the patterns of increase for both fiber types differed between the two programs. These findings suggest that training programs incorporating elements of both "steady-state" incline and high-speed interval running can potentially induce respiratory enzyme adaptations in the greatest spectrum of rodent skeletal muscle fibers in addition to inducing adaptations to enhance contractile potential in cardiac muscle.


Effect of functional overload on enzyme levels in different types of skeletal muscle. The effects of bilateral functional overload on enzyme changes in fast-twitch plantaris muscles were studied on different groups of rats: 1) normal-control; 2) normal-exercise; 3) overload-control; and 4) overload-exercise. Overload was accomplished by surgical elimination of synergists. Exercising groups walked up a 65% grade, 3 m/min, 2 h/day. Peak muscle enlargement of the overload groups was reached after 5 wk. Citrate synthase, phosphofructokinase, and myofibril ATPase activities were consistantly depressed by approximately 30%, 40%, and 18%, respectively, in overload as compared to normal groups. Daily exercise prevented the decrease in only citrate synthase activity. Unilateral overload of medial gastrocnemius muscle indicated that both fast-twitch oxidative-glycogenolytic and fast-twitch glycogenolytic fiber types undergo enzyme changes in response to the functional stress. However, changes in the former were in closer agreement with the net changes seen in the plantaris than the latter. Soleus muscle responded to overload primarily with marked reductions in respiratory capacity. These findings suggest that certain enzyme systems are altered with functional overload in different fiber types. However, the alterations in certain enzyme systems may, in part, be independent of the process of hypertrophy.


Turbulent airflow meter for long-term monitoring in patient-ventilator circuits. A new type of flowmeter is described which operates on the principle that pressure drop (deltaP) produced by turbulent volume flow (V) through a simple resistance chamber obeys a relation of V = K (deltaP)0.50. Data are given showing that the device follows a true power law with a single exponent for airflows ranging from 3.5 to 270 l/min. Standard instrumentation and a linearization circuit are used with the new flowmeter to provide linear steady-state and alternating airflow measurements up to peak rates of 150 l/min and frequency to 15 Hz. Data are presented comparing integrated airflow readings from the new turbulent flowmeter and a laminar-type flowmeter. The turbulent airflow meter appears to offer increased reliability for long-term patient monitoring use in patient-ventilator circuits.


Transformation in Staphylococcus aureus: role of bacteriophage and incidence of competence among strains. When used in a helper phage capacity, phages 29, 52, 52A, 79, 80, 55, 71, 53, 83A, 85, 95, 96, phi11, and 80 alpha, all serological group B Staphylococcus phages, conferred competence for transformation to S. aureus 8325-4, a strain that does not normally become competent. Of the serological group A phages tested, only phage 3A showed significant competence-conferring activity. Phages 29, 55, 53, 83A, .85, 95, phi11, and 80 alpha showed an enhancement of competence-conferring activity if exposure to the cells occurred in the presence of nromal rabbit serum. All of the propagating strains for the Staphylococcus reference typing phages were rendered competent for transformation by exposure to at least one of these helper phages. The use of a helper phage to confer competence to S. aureus did not result in distortion of the genetic linkages observed in an inherently competent strain. Lysogenization by phages phi11 or 83A is shown not to be required for the expression of competence, and evidence is presented which indicates that competence in the inherently competent 8325 strain is due to a helper phage effect initiated by the adsorption to cells of phi11 virion parts [or phi11 particles in the case of the single lysogen 8325-4(phi11)] that have been liberated by prophage induction.


Energy-linked potassium uptake by mitochondria from wild-type and poky strains of Neurospora crassa. Mitochondria from Neurospora crassa, like mammalian mitochondria, carry out rapid, energy-linked K+ uptake and H+ release in the presence of valinomycin. The maximal rate of K+ uptake was about 1.0 mumol/mg of mitochondrial protein per min and was seen at valinomycin concentrations in the range of 100 to 200 mug per mg of mitochondrial protein and at K+ concentrations of 4 mM or above. Uptake could be supported either by substrate oxidation or by adenosine 5'-triphosphate (ATP), and was inhibited in the former case by antimycin or cyanide, in the latter case by oligomycin, and in both cases by 2,4-dinitrophenol. Mitochondria from the cytochrome-deficient mutant poky carried out substrate-driven K+ uptake at reduced rates, but oligomycin-sensitive, ATP-driven K+ uptake at rates about 60% greater than those shown by wild-type mitochondria. This result is consistent with the recent finding (Mainzer and Slayman 1976) that poky contains elevated amounts of oligomycin-sensitive mitochondrial adenosine 5'-triphosphatase activity.


Action of chondroitinases. I. The mode of action of two chondroitinase-AC preparations of different origin. The modes of action of two chondroitinases-AC [EC 4.2.2.5] from Arthrobacter aurescens and Flavobacterium heparinum were examined. By comparison of the increase of viscosity and by analyses of digests using paper chromatography and gel filtration, it was shown that the Arthrobacter enzyme (A-Chase) degrades the substrate by a stepwise attack, while the Flavobacterium enzyme (F-Chase) exhibits a more random attack, though the first attack of both enzymes is of endo-type. Further study was carried out of the initial rate and final extent of the enzymic degradation of various mucopolysaccharides. The order of the initial rates at which the native mucopolysaccharides are degraded was similar for both enzymes. For A-Chase, the initial rate and final extent of degradation of modified chondroitin sulfate C or chondroitin methyl ester, however, were low compared with those of F-Chase. These results also suggested that A-Chase degrades the substrate by stepwise attack and F-Chase by random attack.


Structure and function of the two heads of the myosin molecule. I. Binding of adenosine diphosphate to myofibrils during the adenosinetriphosphatase reaction. 1. The myosin content of myofibrils was found to be 51% by SDS-gel electrophoresis. 2. The initial burst of Pi liberation of the ATPase [EC 3.6.1.3] of a solution of myofibrils in 1 M KCl was measured in 0.5 M KCl, and found to be 0.93 mole/mole of myosin. 3. The amount of ADP bound to myofibrils during the ATPase reaction and the ATPase activity were measured by coupling the myofibrillar ATPase reaction with sufficient amounts of pyruvate kinase [EC 2.7.1.40] and PEP to regenerate ATP. The maximum amount of ADP bound to myofibrils in 0.05M KCl and in the relaxed state was about 1.5 mole/mole of myosin. On the other hand, the ATPase activity exhibited substrate inhibition, and the amount of ATP required for a constant level of ATPase activity was smaller than that required for the maximum binding of ADP to myofibrils. 4. The maximum amount of ADP bound to myofibrils in 0.5 M KCl was about 1.9 mole/mole of myosin. When about one mole of ADP was found to 1 mole of myosin in myofibrils, the myofibrillar ATPase activity reached the saturated level, and with further increase in the concentration of ATP one more mole of ADP was found per mole of myosin.


Structure and function of the two heads of the myosin molecule. II. Separation of the two fractions of subfragment-1 of myosin by affinity column chromatography on immobilized F-actin: direct evidence for acceleration by F-actin of the decomposition of the reactive enzyme-phosphate-ADP complex formed on head B of myosin. F-Actin (FA) and pyruvate kinase (PK) [EC 2.7.1.40] were immobilized on PAB-cellulose. HMM-Subfragment-1 (S-1) was applied to a column of immobilized FA and PK, and eluted with 1-1.5 muM ATP and 1 mM PEP in 50 mM KCl, 2 mM MgCl2, and 10 mM Tris-HCl at pH 7.8 and 4 degrees. The size of the initial burst of Pi liberation of S-1 applied to the column was 0.5 mole/mole S-1. The burst size of S-1 decreased with increase in the fraction number, and S-1 in later fractions showed a burst size of 0.1-0.3 mole/mole. On the other hand, the rate of the ATPase [EC 3.6.1.3] reaction in the steady state was almost independent of the burst size, and increased slightly with increase in the fraction number. The ATPase activity of S-1 with a burst size of less than 0.2 mole/mole was scarcely activated by FA. Usually, the dependence on the burst size of S-1 of its ATPase activity in the presence of FA was sigmoidal, and marked activation by FA was observed when the burst size was larger than 0.3-0.4 mole/mole. Similar results were obtained with S-1 fractions separated by the ultracentrifugation method described in our previous paper ((1976) J. Biochem. 79, 419-434).


Structure and function of the two heads of the myosin molecule. III. Cooperativity of the two heads of the myosin molecule, shown by the effect of modification of head A with rho-chloromercuribenzoate on the interaction of head B with F-actin. Subfragment-1 of HMM was prepared by tryptic [EC 3.4.21.4] digestion of HMM, which had been modified with 1 mole of CMB per mole of HMM at a specific SH group, SHr. S-1(T) obtained from CMB-HMM retained almost all the CMB, and the amount of bound CMB was about 0.8-0.9 mole per 2 moles of S-1(T). S-2 of CMB-HMM contained no bound CMB. The ATPase [EC 3.6.1.3] activity of HMM increased gradually with increase in the concentration of FA, and the acto-HMM ATPase was inhibited by excess substrate or removal of Ca2+ ions in the presence of RP. The ATPase activity of CMB-HMM increased to a maximum level on adding a small amount of FA, and the acto-CMB-HMM ATPase showed neither substrate inhibition nor Ca2+ sensitivity in the presence of RP. On the other hand, the dependence on the concentration of FA of the ATPase activity of acto-S-1(T) was unaffected by modification of S-1 with CMB. The Ca2+ sensitivity of the ATPase activity of acto-S-1(T) in the presence of RP was also unaffected by the modification. Acto-S-1(T) dissociated almost completely, while acto-CMB-S-1(T) was only 50% dissociated on adding ATP. More than 80% of the bound CMB was contained in S-1(T) undissociated from FA. Furthermore, superprecipitation of actomyosin induced by ATP was completely inhibited by adding about 2 moles of CMB-S-1(T) per mole of actin monomer. On the other hand, about 90% of the burst size of Pi liberation was retained in S-1(T) dissociated from FA. It was concluded that the two heads of the myosin molecule are different: one shows the initial burst of Pi liberation, and does not contain the SHr group which binds CMB (head B), and the other does not show the initial burst and contains the SHr group (head A). It was also concluded that modification of head A of HMM or myosin with CMB increases its binding strength to FA, and consequently the substrate inhibition and Ca2+ sensitivity of acto-HMM or actomyosin ATPase at head B are lost on modification of head A with CMB. CMB-S-1(CT) was prepared by chymotryptic [EC 3.4.21.1] digestion of CMB-myosin, and separated into two fractions by ultracentrifugation of acto-CMB-S-1(CT) in the presence of ATP. Three components of CMB-S-1(CT) with molecular weights of 9, 2.4, and 1.2 X 10(4) were separated by SDS-polyacrylamide gel electrophoresis. The ratios of the peak areas of the three components in electrophoretograms were the same in CMB-S-1(CT) and in the two fractions (1 : 0.18 : 0.09), indicating that heads A and B have the same subunit structure.


Structure and function of the two heads of the myosin molecule. IV. Physiological functions of various reaction intermediates in myosin adenosinetriphosphatase, studied by the interaction between actomyosin and 8-bromoadenosine triphosphate. The kinetic properties of the hydrolyses of 8-Br ATP and 8-SCH3 ATP by myosin [EC 3.6.1.3] and actomyosin were compared with those of ATP, and the following results were obtained. The Ca-NTPase activities of myosin using these two ATP analogs as substrates were smaller than that of ATPase, and the NTPase activities toward these analogs were strongly suppressed by EDTA. The Mg-NTPase activities toward these analogs were higher in a medium of high ionic strength than in a medium of low ionic strength, in contrast to the activity of Mg-ATPase. These analogs did not produce any initial burst of Pi liberation, activation of myosin NTPase by F-actin, or superprecipitation of actomyosin. The interactions between 8-Br ATP and HMM, acto-HMM, actomyosin, and myofibrils were studied in detail in the presence of Mg2+ in medium of low ionic strength. The Michaelis constant, Km, and the maximum rate, Vm, of 8-Br ATPase of HMM were 27 muM and 21 min-1, respectively. The fluorescence change of HMM induced by 8-Br ATP also followed the Michaelis-Menten equation, and the Michaelis constant, Kf1, was as low as 4 muM. Acto-HMM and acto-S-1 were fully dissociated by the addition of 8-Br ATP. The relation between the extent of dissociation of acto-HMM and the concentration of 8-Br ATP followed the Michaelis-Menten equation, and the apparent dissociation constant, Kd, was 22 muM. This Kd value is almost equal to the Km value of 8-Br ATPase of HMM described above. Myofibrillar contraction was not supported by 8-Br ATP. It was concluded that in the myosin NTPase reaction with 8-Br ATP as a substrate, M2NTP but not MNDPP is formed in route (1), while MNTP is formed in route (2). It was also concluded that the key intermediate for the actomyosin NTPase reaction is MNDPP, and that dissociation of acto-HMM is induced by the formation of M2NTP and MNTP in routes (1) and (2), respectively.


Characterization of the nucleoside triphosphate phosphohydrolase (ATPase) activity of RNA synthesi termination factor p. I. Enzymatic properties and effects of inhibitors. The purification of p protein to homogeneity from Escherichia coli has shown that its RNA-dependent ATPase activity is physically inseparable from its termination activity. The biochemical properties of pATPase have been studied using poly(C) as the activating RNA. This reaction is stimulated by Mg2+ ions and Mn2+ ions and is prevented by excess EDTA; it is not stimulated by Ca2+ ions. The reaction is not affected by a Zn2+ ion chelator and is inhibited by 1 mM Zn2+. With Mg2+ present, the activity is essentially constant from pH 7 to pH 9.7. pATPase is sensitive to p-hydroxymercuribenzoate and to N-ethylmaleimide. All four ribonucleoside triphosphates are hydrolyzed by p action. ATP has the lowest Km (0.009 mM), while CTP has the highest Vmax. In a mixture containing all four nucleoside triphosphates at a concentration of 0.4 mM, p shows no strong preference for any one of the substrates. The response of p ATPase to a variety of inhibitors of other ATPases and GTPases and of transcription has been studied. Of the compounds tested, aurintricarboxylic acid, an inhibitor of protein-nucleic acid interactions, was found to be a potent inhibitor of p ATPase, while rifampicin and heparin had no effect. pATPase showed partial sensitivity to thiostrepton, fusidic acid, Dio 9, and sodium azide.