Randomness tests on the sequence of ascal segregation classes in Neurospora crassa. Various statistical tests for randomness were made on the order of ascal classes in groups of asci from wild-type X asco crosses. There was no significant nonrandom clustering of asci of the same segregation class, nor a regular twinning of similar asci. Any apparent observed clustering of similar ascal classes is probably an artefact or due to chance. 2 x n X2 tests showed that frequencies of individual ascus classes from different perithecia were generally homogeneous, as were second division segregation frequencies. The tests described here for randomness in sequences of occurrences could be of general use in other areas of genetics.


National gonorrhea therapy monitoring study: adverse drug reactions. The Center for Disease Control and cooperating clinics monitored adverse drug reactions in 6,969 patients who were treated for suspected uncomplicated gonorrhea with one of the four 1972 United States Public Health Service (USPHS) recommended regimens and returned for reexamination. Of those patients receiving the aqueous procaine penicillin G (APPG)-probenecid regimen, 2.0% had at least one adverse reaction and 0.18% experienced procaine reactions. No life-threatening reactions occurred. The overall reaction rates for the ampicillin-probenecid, tetracycline and spectinomycin regimens were 0.62%, 5.9%, and 0.61%, respectively. Our findings document the relative safety of the USPHS recommended regimens.


Acupuncture: clinical trials in the horse. A discussion of the merits of acupuncture therapy and a review of experiments that support the neurogenic mediation of acupuncture are presented. Case reports are included as examples of the therapeutic value of acupuncture in treatment of intestinal and musculoskeletal disorders in the horse. Statistical importance cannot be credited to the clinical experiences reported here because of the small number of cases. Hopefully, the clinical success reported will encourage continued investigation of the clinical efficacy and adjunctive value of acupuncture in the veterinary profession.


Cytochemical characterization of the myoepithelial cells in palatine glands. Myoepithelial cells of rat and mouse palatine glands are similar in fine structural appearance to those of other exocrine glands and smooth muscle cells. Myoepithelial cells reveal fibrils, and vesicular structures comparable to pinocytic or surface vesicles of smooth muscle cells. Lanthanum-impregnated preparations of the gland reveal that many of these vesicle-like structures are, in fact, invaginations of the plasma membrane and are continuous with the extracellular space. Observations on glandular tissue incubated for the demonstration of ATPase and adenylate cyclase have indicated that a high level of activity of these two enzymes is localized in the plasma membrane of the myoepithelial cells facing the acinar cells, and in vesicular structures along this membrane. The possibility that these enzyme activities are related to contractility of myoepithelial cells is discussed.


Effect of spectinomycin on peptide chain initiation. Spectinomycin inhibits the formation and causes dissociation of performed specific cell-free initiation complexes prepared with the trinucleotide A-U-G or R17 phage RNA, fmet-RNAF and either 30S ribosomal subunits or 70S ribosomes. Both the initiation factor and the Mg2+-induced processes are subject to inhibition by spectinomycin. The only exception is the Mg2+-induced 70S initiation system formed with A-U-G which is stimulated by spectinomycin.


Reflex control of expiratory airflow and duration. Unanesthetized, unrestrained cats were studied repeatedly after placement of a permanent tracheostomy, catheters for respiratory pressure measurements, and respiratory muscle EMG electrodes. The tracheostomy was opened or closed by a remote mechanism. Opening the tracheostomy reduced tracheal pressure to zero and diverted flow from the upper airway; closing the tracheostomy reestablished the normal pathway for airflow. Opening the tracheostomy during expiration evoked reflex responses in the diaphragm, in the laryngeal abductor and in abdominal expiratory muscles. These were sustained compensatory ("tracking") responses which, in each case, acted to offset loss of expiratory braking by the upper airway. Occlusion of the tracheostomy during expiration produced the opposite responses. Responses to tracheostomy opening usually overcompensated for the loss of upper airway resistance, suggesting that extrathoracic tracheal receptors may participate in tracking. Changes in the expiratory time course of lung volume were accompanied by changes in the duration of expiration. These "triggering" responses were shown to operate independently of the tracking responses though both were eliminated by vagotomy.


Characterization of ATPases of plain synaptic vesicle and coated vesicle fractions isolated from rat brains. The plain synaptic vesicle and the ocated vesicle fractions were isolated from rat brains, and the ATPase [EC 3.6.1.3] activities were characterized in terms of ionic effects, drug effects, and protein components. Coated vesicle fraction contained three times as much actomysin-like proteins as plain vesicle fraction, although both fractions had an identical ratio of actin-like protein to myosin-like protein. The ATPases of these two fractions were activated by both Mg2+ and Ca2+, and, in the presence of either of the cations, were inhibited by KCl. Reserpine activated plain vesicle ATPase only in the presence of Cl-. Colchicine and vinblastine inhibited coated vesicle ATPase only. The results are consistent with the view that actomyosin-like proteins are involved in the synaptic retrieval process.


Separation of myosin subfragment 1 into two fractions, one having the burst site and the other having the non-burst site. During Mn(II)-ATP hydrolysis by myosin, the predominant intermediate formed at the burst site of the enzyme below 10 degrees is the myosin-ADP complex formed by adding ADP to myosin, while above 10 degrees it is the myosin -ADP-P1 complex generated by ATP hydroolysis (Yazawa, Morita, & Yagi (1973) J. Biochem. 74, 1107; Hozumi & Tawada (1975) Biochim. Biophys. Acta 376, 1; Tawada & Yoshida (1975) J. Biochem. 78, 293). It is suggested that the second (non-burst) site of myosin predominantly forms the myosin-ATP complex (Hozumi & Tawada, ibid.). From these findings, it is expected that (i) myosin subfragment 1 (S1) having the burst site is bound to actin in Mn(II)-ATP solution containing ADP below 10 degrees, because it forms the S1-ADP complex even in the presence of ATP; (ii) the other S1, i.e., that having the non-burst site, is dissociated from actin, because it forms the S1-ATP complex. These two expectations were confirmed by viscosity measurements of acto-S1 solutions, giving a basis for the separation of S1 into two fractions: one having the burst site and the other having the non-burst site. S1 having the non-burst site could be extracted from partially papain [EC 3.4.22.2]-digested myofibrils of rabbit skeletal muscle with a solution containing MnCl2, ATP, and ADP at 0 degrees. S1 having the burst site was extracted from myofibrils already used for the extraction of S1 having the non-burst site, with a solution containing MgCl2 and ATP at 20 degrees. The former S1 fraction had Mg-ATPase [EC 3.6.1.3] activity, but scarcely showed any initial burst of Pi liberation. The latter S1 showed a Pi burst of more than 0.5 (M/M). The steady state ATPase activity of the former S1 was slightly higher than that of the latter. The burst size of normal S1, i.e., that extracted from papain-digested myofibrils with Mg-PPi or Mg-ATP, was 0.5 (M/M). The ultraviolet absorption spectrum of the non-burst type S1 was not changed by ADP but was changed by ATP, though the difference spectrum was distinct from that of normal S1 and the difference molar extinction coefficient at 289 nm was only 20% of that of normal S1. No significant difference was seen in the compositions of these two S1's and normal S1, as determined by SDS gel electrophoresis.


Purification from Acanthamoeba castellanii of proteins that induce gelation and syneresis of F-actin. From Acanthamoeba castellanii, we have purified four proteins each of which alone causes a solution of F-actin to gel. The four active proteins have subunit molecular weights of about 23,000, 28,000, 32,000 and 38,000, respectively; the last three may be dimers in their native proteins. Together, these four proteins account for about 97% of the gelation activity of the whole extract; not more than about 3% of the total activity of the unfractionated extract can be due to a 250,000-dalton polypeptide. Another protein fraction, purified by agarose chromatography, induces shrinking (syneresis) of gels formed from F-actin and any of the gelation factors. That fraction contains a high Ca2+-, low (K+,EDTA)-ATPase and a major polypeptide of 170,000 daltons both of which bind to actin in the shrunken gel pellet. The active fraction does not contain the previously described Acanthamoeba myosin (Pollard, T. D., and Korn, E. D. (1973) J. Biol. Chem. 248, 4682-4690).


Purification and properties of the P15 specific restriction endonuclease from Escherichia coli. The specific restriction endonuclease of the Escherichia coli plasmid, P15, has been purified to apparent homogeneity by a procedure that includes DNA-cellulose chromatography as well as a new endonuclease assay. Sedimentation on glycerol gradients showed two peaks of activity with values of 11.3 S and 15.7 S. The highly purified enzyme requires ATP and Mg2+ for activity and is stimulated by S-adenosylmethionine. A methylase activity is observed in the course of the endonucleolytic reaction which protects some of the DNA sites from cleavage.


Activation of human plasminogen by equimolar levels of streptokinase. Native Glu-human plasminogen (Mr approximately 92,000 with NH2-terminal glutamic acid) is able to combine directly with streptokinase in an equivalent molar ratio, to yield a stoichiometric complex. The plasminogen moiety in the complex then undergoes streptokinase-induced conformational changes. As a result of such, an active center develops in the plasminogen moiety of the complex. This proteolytically active complex then activates plasminogen in the complex to plasmin and at least two peptide bonds are cleaved in the process. The data presented in this paper reveal that initially an internal peptide bond of plasminogen (in the complex) is cleaved to yield a two-chain, disulfide-linked plasmin molecule. The heavy chain (Mr approximately 67,000 with NH2-terminal glutamic acid) of this plasmin molecule has an identical NH2-terminal amico acid as the native plasminogen. The light chain (Mr approximately 25,000 with NH2-terminal valine) of plasmin is known to be derived from the COOH-terminal portion of the parent plasminogen molecule. A second peptide is then cleaved from the NH2-terminal end of the heavy chain of plasmin producing a proteolytically modified heavy chain (Mr =60.000 with NH2-terminal lysine). This cleavage of the NH2-terminal peptide from the heavy chain of plasmin is shown to be mediated by the dissociated free plasmin present in the activation mixture. Plasmin in the streptokinase-plasmin complex is unable to cleave this NH2-terminal peptide. This same NH2-terminal peptide can also be cleaved from native Glu-plasminogen or from the Glu-plasminogen-streptokinase complex by free plasmin and not by a complex of streptokinase-plasmin. From these studies we conclude (a) in the streptokinase-plasminogen complex, the NH2-terminal peptide need not be released prior to the cleavage of the essential Arg-Val peptide bond which leads to the formation of a two chain plasmin molecule and (b) that this peptide is cleaved from the native plasminogen or from the heavy chain of the initially formed plasmin in the streptokinase complex by free plasmin and not by the plasmin associated with streptokinase. In agreement with this, plasmin associated with streptokinase was unable to cleave the NH2-terminal peptide from the isolated native heavy chain possessing glutamic acid as the NH2-terminal amino acid; whereas free plasmin readily cleaved this peptide from the same isolated Glu-heavy chain.


Phosphorylation from adenosine triphosphate of sodium- and potassium-activated adenosine triphosphatase. Comparison of enzyme-ligand complexes as precursors to the phosphoenzyme. The relative effectiveness of the ligands Mg2+, Na+, and ATP in preparing sodium plus potassium ion transport adenosine triphosphatase for phosphorylation was studied by means of a rapid mixing apparatus. Addition of 2 mM MgC12, 120 mM NaC1, and 5 muM [gamma-32P]ATP simultaneously to the free enzyme gave an initial phosphorylation rate of about 0.3 mu mol-mg-1-min-1 at 25 degrees and pH7.4. Addition of Mg2+ to the enzyme beforehand, separately or in combination with Na+ or ATP, had little effect on the initial rate. Addition of Na+ only to the enzyme beforehand increased this rate 1.5- to 3-fold. Early addition of ATP 130 ms before Na+ plus Mg2+ increased the rate 6- to 7-fold. Early addition of Na+ plus ATP was most effective; it increased the rate about 10-fold. The data indicate that Na+ and ATP bind in a random order and that each ligand potentiates the effect of the other. The rate of dissociation of ATP from the enzyme was estimated by a chase of unlabeled ATP of variable duration. This rate was slowest in the presence of Mg2+ (k = 540 min-1), most rapid in the presence of Na+ (k = 2000 min-1), and intermediate (k = 1100 min-1) in the absence of metal ions. The effect of Na+ concentration on the rate of phosphorylation was estimated when Na+ with Mg2+ was added to the enzyme-ATP complex. The rate followed Michaelis-Menten kinetics with a maximum of 2.9 mu mol-mg-1 and a Km of 8 mM. The effect of Na+ concentration was also estimated on the increment in the rate of phosphorylation produced by the presence of Na+ with the enzyme-ATP complex beforehand. The increment followed the same kinetics with a maximum of 3.75 mu mol-mg-1-min-1 and a Km of 5.4 mM. In both cases estimation of the Hill coefficient failed to show cooperativity between binding sites for Na+. In contrast, the dependence of ouabain-sensitive ATPase activity on Na+ concentration in the absence of K+ indicated two sites for Na+ with apparent Km values of 0.16 and 8.1 mM, respectively.


A protein inhibitor of mitochondrial adenosine triphosphatase (F1) from Saccharomyces cerevisiae. A heat-stable protein has been detected in Saccharomyces cerevisiae which inhibits mitochondrial ATPase activity. The protein inhibitor has been isolated from extracts prepared by brief heat treatment of unbroken cell suspensions. The isolated inhibitor is a small basic protein (molecular weight close to 7000, isoelectric proint 9.05) devoid of tryptophan, tyrosine, and cysteine as well as proline. The NHP2-terminal amino acid is serine. The ultraviolet absorption spectrum shows the vibrational fine structure of the phenyl-alanine band. Like the ATPase inhibitor from bovine heart mitochondria the yeast inhibitor is rapidly destroyed by trypsin. It is also inactivated by the yeast proteinases A and B. Radioimmunological analysis indicates that the inhibitor is synthesized on cytoplasmic ribosomes. Its accumulation seems to be connected to the formation of the mitochondrial ATPase complex, since its specific activity is greatly reduced both in extracts obtained from the F1-ATPase-deficient nuclear mutant pet 936 and from the cytoplasmic petite mutant D 273-10B-1.


Effect of uncoupler on "downhill" substrate efflux of Escherichia coli is dependent on (Mg2+, Ca2+). Adenosine triphosphatase. Previous studies have shown that mutations in the unc gene of Escherichia coli K12 cause defects in energy transduction as well as a membrane-bound (Mg2+, Ca2+)-adenosine triphosphatase. We studied the effect of this mutation on the "downhill" efflux of methyl-beta-D-galactopyranoside, a suboli K12 did not show significant differences in substrate influx of efflux, a differential effect of an uncoupler, 2,4-dinitrophenol was demonstrated. In contrast to the unc+, dinitrophenol failed to inhibit significantly the rate coefficient of efflux in the unc- strain. Analysis of spontaneous unc+ revertants of the unc- mutant provided additional evidence that a functional unc gene is necessary for dinitrophenol inhibition of efflux. Other uncouplers tested in the unc+ strain showed different effects on efflux. While arsenate, azide and carbonyl cyanide p-trifluoromethoxyphenulhydrazone caused little or no effect, 2,4-dibromophenol and pentachlorophenol increased efflux by a considerable factor.


Transport of nutrients by a thermophilic bacterium--reconstruction of vesicles from crystalline ATPase or solubilized alanine carrier. A strain of aerobic thermophilic bacteria was selected in order to purify highly stable membrane proteins and no reconstitute proteoliposomes capable of transporting nutrients from them. These proteins responsible for the transport could be divided into (1) proteins which supply energy to the transporting system, and (2) specific nutrient carriers driven by the energy. The former included a stable ATPase (TF1) and a lipoprotein TF0) which rendered TF1 sensitive to energy transfer inhibitors. The complex of TF0 anlysis of ATP. And one of the latter reported in this paper was alanine carrier protein which was driven by proton movement. TF1 was the first crystallized ATPase in biomembranes, and was reconstituted from its five different polypeptides, two of which were necessary for ATPase activity and four of which, for proton translocation. Purification of alanine carrier and reconstitution of proteoliposomes capable of alanine accumulation were also demonstrated.


Why do tumor cells have a high aerobic glycolysis? In Ehrlich ascites cells and several other tumors, the high aerobic glycolysis is maintained by generation of ADP and Pi by the plasma membrane Na+K+ ATPase. The high ATP activity is caused by a defective pump that operates at a low efficiency. Studies of the mechanism of action of the Na+K+ ATPase and other pump ATPases suggest several alternative mechanisms that might account for the decreased efficiency. The possibility of involvement of a proteolipid is under investigation.


Differences in neutral amino acid and glucose transport between brush border and basolateral plasma membrane of intestinal epithelial cells. A comparison of L-valine and D-glucose transport was carried out with vesicles of plasma membrane isolated either from the luminal (brush border) or from the contra-luminal (basolateral) region of small intestinal epithelial cells. The existence of transport systems for both non-electrolytes was demonstrated by stereospecificity and saturability of uptake, as well as tracer coupling. Transport of L-valine and D-glucose differs markedly in the two types of plasma membrane with respect to stimulation by Na+. The presence of Na+ stimulated initial L-valine and D-glucose uptake in brush border, but not in basolateral membrane. Moreover, an electro-chemical Na+ gradient, oriented with the lower potential on the inside, supported accumulation of the non-electrolytes above medium concentration only in the brush border membrane. L-Valine and D-glucose transport also were saturated at lower concentrations in brush border (10-20 mM) than in basolateral plasma membranes (30-50 mM). A third difference between the two membranes was found in the effectiveness of known inhibitors of D-glucose transport. In brush border membranes phlorizin was more potent than phloretin and 2', 3', 4'-trihydroxy-4-methoxy chalcone and cytochalasin B did not inhibit at all. In contrast, with the basolateral plasma membranes the order of potency was changed to phloretin = 2',3',4'-trihydroxy-4-methoxy chalcone greater than cytochalasin B greater than phlorizin. These results indicate the presence of different types of transport systems for monosaccharides and neutral amino acids in the luminal and contra-luminal region of the plasma membrane. Active transepithelial transport can be explained on the basis of the different properties of the non-electrolyte transport systems in the two cellular regions and an electro-chemical Na+ gradient that is dependent on cellular metabolism.


Genetic alteration in the (Na+ + K+) ATPase transport system expressed in human lymphoblasts and their isolated plasma membranes. A series of ouabain-resistant human lymphoblastoid lines were shown to be genetically altered in the (Na+ + K+) ATPase transport system. The sensitivity to ouabain of Rb+ uptake in intact cells and (Na+ + K+) dependent ATP hydrolysis in purified plasma membrane vesicles was compared with measurement of ouabain binding to intact cells. Preliminary evidence for at least two categories of ouabain resistance was obtained.


Heparan sulfates of mouse cells. Analysis of parent and transformed 3T3 cell lines. Heparan sulfate from the surface of a variety of mouse cells at different cell densities was examined by ion-exchange chromatography. The results of this analysis show that: (1) The heparan sulfate from new isolates of Swiss 3T3 cells transformed by SV40 virus (a DNA tumor virus) elutes from DEAE-cellulose at a lower ionic strength than that from the parent cell type. This finding confirms our earlier observation with an established SV40-transformed cell line (Underhill and Keller, '75) and eliminates the possibility that this change is caused by extended passage in culture. (2) For both parent and transformed 3T3 cells, the heparan sulfates from low and high density cultures were the same as judged by chromatography on DEAE-cellulose. This result demonstrates that the transformation-dependent change which we have observed is independent of cell density. (3) The heparan sulfate from Balb/c 3T3 cells transformed with Kirsten murine sarcoma virus (an RNA tumor virus) elutes from DEAE-cellulose prior to that from parent Balb/c 3T3 cells. This result extends the transformation dependent change in heparan sulfate to the Balb/c 3T3 cell line and to cells transformed with an RNA virus.


Nature of lectin-induced alteration of potassium transfer in Ehrlich ascites tumor cells. The way in which the lectins concanavalin A (Con A) and Ricinus communis agglutinin (Ricin) alter the K+ content of Ehrlich ascites tumor cells was investigated. Unidrectional and net fluxes were determined in unwashed cells during a time course following lectin addition. Total influx, ouabain sensitive influx, Mg++- and Na+-K+-ATPase activity were all unaffected. Cell ATP content was normal for at least 19 minutes after exposure to Con A. Early after contact with Ricin or Con A efflux was stimulated 2-3-fold, resulting in net K+ loss, but after 20 minutes efflux had returned to normal. Ricin and Con A acted similarly although Ricin was present at only 1/50 the concentration of Con A. When the findings are evaluated together with previous work it is suggested that a particular membrane glycoprotein may be concerned in the efflux alteration observed.


The effects of fluoxymesterone administration on testicular function. Long term daily administration of fluoxymesterone (9alpha-fluoro-17alpha-methyl-11beta, 17beta-dihydroxyandrost-4-en-3-one) was associated with a modest suppression of sperm production and a profound suppression of testosterone levels in the absence of significant effects on plasma gonadotropin levels. Nine normal male volunteers took either 10, 20, or 30 mg of fluoxymesterone daily for twelve weeks. Plasma samples were obtained for testosterone, estrogen, LH and FSH levels at biweekly intervals before, during and for up to 12 weeks after fluoxymesterone treatment. Samples were obtained for dehydroepiandrosterone sulfate, testosterone binding globulin and free testosterone assays at representative times before, during and after treatment. Although lower sperm counts were observed at several points during both the treatment and follow up periods, significant consistent suppression of spermatogenesis could not be demonstrated. Reduced plasma testosterone levels were seen within 24 h after beginning fluoxymesterone, and further reductions were noted throughout the treatment period. Changes in plasma estrogen levels did not correlate with fluoxymesterone administration. Neither plasma LH nor plasma FSH levels were significantly altered by fluoxymesterone. A short term study utilizing a single dose of fluoxymesterone yielded similar findings. It is proposed that fluoxymesterone has a local effect on the Leydig cell which is not mediated by gonadotropins.


Studies of the diurnal pattern of plasma corticosteroids and gonadotropins in two cases of feminizing adrenal carcinoma: measurements of estrogen and corticosteroid production. Two adult men with feminizing adrenal cortical carcinoma had measurements of their 24-h plasma corticosteroid and gonadotropin patterns as well as 24-h mean hormone levels of estradiol, estetrol, 11-desoxycortisol, DHEA-S, DHEA and testosterone. Cortisol, 11-desoxycortisol and estrogen production rates were also measured. The 24-h corticosteroid patterns showed preservation of the normal 24-h episodic and circadian patterns, albeit at higher levels. The cortisol production rates were markedly elevated despite only moderate elevation of the 24-h mean cortisol level. There were elevated plasma 11-desoxycortisol levels and a markedly elevated 11-desoxycortisol production rate in one patient and THS excretion in the other. The plasma estradiol levels, urinary excretion and production rates were markedly elevated. In addition, there was a decrease in the specific activity of estriol compared with estrone and estradiol as well as measurable levels of estetrol in both patients. These latter observations coupled with the urinary immunoassayable hCG in one patient suggest that these tumors may be functioning like trophoblastic tissue. The possibility that estetrol may serve as an additional marker for tumors of trophoblastic origin is of additional interest.


Double-blind study of ipratropium bromide, a new anticholinergic bronchodilator. The efficacy and acceptability of ipratropium given by metered-dose inhaler were evaluated in two double-blind crossover tests against placebo, one preceding and one following a 2-wk period of continual open-label ipratropium treatment. Ten patients with chronic bronchitis and 10 with bronchial asthma participated. Ipratropium produced increase in FEV 1 of more than 15% within 5 min of inhalation, and this effect was maintained for 4 to 5 hr. Statistically significant mean increases over the FEV 1 baseline values were recorded after ipratropium treatment in both the initial and the final crossover tests. There were no adverse reactions to any of the placebo or ipratropium test doses or to the ipratropium treatment. Serial electrocardiograms, laboratory tests, blood pressure, and pulse rate showed no change from lthe baseline. Sputum volume and dry-weight determinations in the patients with bronchitis before and after the 14-day treatment revealed no changes.


A comparison of the bronchodilator activity of Sch 1000 and salbutamol. The effects of the beta 2-adrenergic agonist, salbutamol, 200 mug, and the cholinergic antagonist, Sch 1000, 40 mug, have been compared in 25 asthmatic patients using a single dose, double-blind, crossover trial design. Salbutamol aerosol produces a greater degree of bronchodilatation than Sch 1000 aerosol during the initial three hours following drug administration. There is no significant difference in the bronchodilator effects of the two drugs in the interval four to eight hours after drug administration. Nonatopic patients showed less difference in bronchodilator response to each of the two drugs than atopic patients. Neither drug showed any significant adverse effect on blood pressure, pulse rate, or electrocardiogram. In six asthmatic patients the effect of the combination of salbutamol, 200 mug, and Sch 1000, 40 mug, was evaluated. The combination produced a longer duration of bronchodilatation than either drug alone when compared to placebo.


Symposium on arthritis in older persons. Section III. Osteoarthritis and back pain. Examination of the back in the geriatric patient. Older people often complain of back pain, but it usually is not a major complaint except in the presence of serious disease such as malignancy, compression fractures from osteoporosis, or disc-space infections. When back pain is a serious symptom in the elderly patient, the physician should look beyond the obvious evidences of degenerative joint disease for these other more serious conditions. Satisfactory examination of the back does not require an undue amount of time. It is important that it be done systematically. Simple, rapid, and adequate procedures are described.


Back pain: osteoarthritis.

Back pain: osteoarthritis. Back pain is one of the chief complaints of the elderly. It may be either a chronic deep skeletal muscular pain or an acute circumscribed pain arising from nerve-root irritation. The main causes of back pain in older people are: 1) degenerative changes (spondylosis, osteoarthritis, ankylosing hyperostosis); 2) malignancy (multiple myeloma, metastases from carcinoma or lymphoma); and 3) metabolic disorders (osteoporosis, osteomalacia, chondrocalcinosis, Paget's disease). Mechanisms and variations are discussed in detail.


Females and illness: recent trends in sex differences in the United States. Data from the national Health Interview Survey for 1957-72 show that females have higher age-standardized rates of acute conditions, chronic conditions, and disability due to acute conditions, compared to males. More males, however, suffer limitations of activity or mobility due to chronic conditions, Females' excess morbidity for acute conditions persists when reproduction-related events are excluded. From 1957-72, females' disadvantage for acute conditions continues unchanged. But for chronic conditions, males are "catching up" to females in overall prevalence, and their conditions are becoming more severe relative to females'. These trends are compatible with trends in sex mortality differences over the same period. Four types of explanation are advanced to account for females' excess morbidity: interview behavior, illness behavior, acquired health risks, and inherited health risks. Empirical evidence suggests the first two factors inflate female rates compared to males; the last two do the opposite. It is hypothesized that excess female morbidity is due primarily to social and psychological factors, and a procedure to test this is stated.


HLA antigen studies in a family with C2 deficiency. Two children in a family were found to be homozygous for C2 deficiency; both parents and a third child were heterozygous. C2 deficiency was associated with the HLA haplotypes carrying the antigens B18 and DW2. Antigen A10 was absent in this family. Mixed lymphocyte culture studies among the family members confirmed the association of C2 deficiency with the HLA-D locus.


A reevaluation of fatty acids as inflammatory agents in acne. The currently widely held theory that intrafollicular free fatty acids (FA) are the primary agents instigating inflammatory changes in acne is based on circumstantial evidence. There is no direct evidence that FA in physiologic concentrations are inflammatory. In the present study the quantities of FA present in isolated pilosebaceous ducts and in isolated comedones were analyzed. Using these values, the effect of FA on intracutaneous injection into human skin was investigated. The range of FA in 257 isolated pilosebaceous ducts from skin of the upper back of 10 male subjects was 0.19 to 2.43 mug, with an average of 0.89 +/- 0.75 mug of FA per duct. The mean FA content in 45 open comedones was 63.6 +/- 24.8 mug per comedone. Fatty acids for intracutaneous testing were isolated from human skin surface lipids and from hydrolyzed triglycerides purified from pooled isolated sebaceous glands. Twenty-six subjects received 100 mug of FA intracutaneously in the upper back. The response to FA injections could not be distinguished from the response to saline control injections. By 24 hr no erythema, induration, or any visible marks of inflammation were present in the skin of any of the subjects tested. At the histologic level a mild inflammatory infiltrate consisting perdominantly of lymphocytes was slightly more marked in the FA injection site than in the saline control injection site. Increasing the amount of FA injected to 500 mug still produced no visible inflammatory response in human skin. We conclude that intracutaneous injections of FA in physiologic concentrations do not produce more than a very mild inflammatory reaction in human skin and suggest that the role of Propionibacterium acnes in the pathogeneisis of acne may be more complex than merely as a source of intrafollicular lipases.


Interaction of 16beta-hydroxydehydroepiandrosterone with renal mineralocorticoid receptors. A previously unidentified mineralocorticoid, 16beta-hydroxydehydroepiandrosterone (16beta OH-DHEA) has recently been isolated from urine extracts of patients with low-renin hypertension and reported to possess one-fortieth the mineralocorticoid potency of aldosterone by bioassay. However, using a radioreceptor assay, we demonstrate the affinity of 16beta-OH-DHEA for renal 3H-aldosterone receptors to be only 0.011 per cent that of unlabeled aldosterone. 16beta-OH-DHEA therefore would not be expected to possess significant mineralocorticoid properties unless its mechanism of action involves binding to a unique class of renal receptors. Until these discrepancies between bioassayable mineralocorticoid activity and affinity for mineralocorticoid receptors can be resolved, the role of 16beta-OH-DHEA in the pathogenesis of low-renin hypertension remains speculative.


[Determination of oestrogens in pregnancy (author's transl)]. The chemistry of oestrogens, and the metabolism of the oestrogens during pregnancy is considered. On this basis, appropriate methods of oestrogen determination have been devised for the recognition of foetuses at risk; the diagnostic significance of these methods is discussed. A method is regarded as suitable if the results can be quickly available, and give a reliable representation of the rate of oestriol production by the foeto-placental unit. Following a review of the development of eostrogen determinations, one method for the photometric measurement of total urinary oestrogens and one method for the radio-immunological determination of serum oestriol are discussed in detail. The advantages and disadvantages of studies on urine and serum are summarized in a table. Finally, problems in the clinical evaluation of the results of oestriol determinations are discussed.


Tension generation by threads of contractile proteins. Threads of contractile proteins were formed via extrusion and their isometric tensions and isotonic contraction velocities were measured. We obtained reproducible data by using a new and sensitive tensiometer. The force-velocity curves of actomyosin threads were similar to those of muscle, with isometric tensions of the order of 10g/cm2 and maximum contraction velocites of the order of 10(-2) lengths/s. The data could be fitted by Hill's equation. Addition of tropomyosin and troponin to the threads increased isometric tension and maximum contraction velocity. Threads which contained troponin and tropomyosin required Ca++ for contraction and the dependence of their isometric tension on the level of free Ca++ was like that of muscle. The dependence of tension or of contraction velocity upon temperature or upon ionic strength is similar for actomyosin threads and muscle fibers. In contrast, the dependence of most parameters which are characteristic of the actomyosin interaction in solution (or suspension) upon these variables is not similar to the dependence of the muscle fiber parameters. The conclusion we have drawn from these results is that the mechanism of tension generation in the threads is similar to the mechanism that exists in muscle. Because the protein composition of the thread system can be manipulated readily and because the tensions and velocities of the threads can be related directly to the physiological parameters of muscle fibers, the threads provide a powerful method for studying contractile proteins.


Muscular dysgenesis in the mouse (mdg/mdg). I. Ultrastructural study of skeletal and cardiac muscle. Muscular dysgenesis (mdg/mdg), transmitted as an autosomal recessive trait in the mouse, is characterized by a total inability to contract any skeletal muscle. In addition, there is fixation of posture at multiple joints at the time of birth (arthrogryposis multiplex congenital). This muscular disorder has been studied by light, phase and electron microscopic techniques, combined with cytochemical methods. The homozygous mutant fetuses (mdg/mdg) and their littermates(+/?) were studied at time intervals of from 18 to 20 days of gestation. Four litters of non mdg mice (+/+) resulting from the matings of Harvard white mice also served as controls. Structural alterations were found both in cardiac ancd skeletal intrafusal and extrafusal muscle. These changes were characterized by a deviation in the course of muscle development. The most significant change was considered to be in the contractile substance, particularly in the Z band structure. Changes in the sarcotubular system and the retarded development of the motor end plate appeared to result from this primary abnormality in contractile substance. Contraction bodies were consistently located close to close to the motor end plate. The presence of contraction bodies, and the failure of muscle-tendon junctions to form seemed to be related to an alteration of the contractile filaments. Limited longitudinal growth of the muscle fibers and disorganization of myofibrils were attributed to the incomplete development of the Z band.


Surgical management of massive ventral hernias in children. The management of 7 children with massive abdominal wall hernias is reviewed, utilizing a technique of stabilizing the defect by insertion of a Teflon mesh prosthesis followed by pneumoperitoneum and staged reduction. Teflon mesh has proven ideally suited for this purpose because of its flexibility, elasticity, and relative nonreactivity, allowing it to be applied directly over the surface of exposed bowel without inducing fistula formation. Although the mesh is securely incorporated into the fascial perimeter of the abdominal wall, a pseudomembrane is formed at the point of contact with the bowel surface which allows subsequent dissection and removal of the prosthesis with relative ease. Having limited the size of the defect by insertion of the mesh, an ideal situation is created for use of pneumoperitoneum to expand the peritoneal cavity and stretch the normal tissues of the abdominal wall, thus facilitating subsequent operative reduction of the ventral hernia. Utilizing this approach, excellent cosmetic and functional results have been achieved in all 7 patients.


Laparoscopy in childhood.

Laparoscopy in childhood. The indications and technique for laparoscopy in childhood are discussed. During the last 5 years 59 laparoscopies were carried out in the Surgical Department of the University Children's Hospital, Zürich, Switzerland, These cases are described in some detail. No complications were encountered.


Estrogens in maternal plasma following intraamniotic injection of (3H)-dehydroepiandrosterone-sulfate in midpregnancy. In 4 patients with normal pregnancies between the 18th and 20th week of gestation (3H7alpha)-dehydroepiandrosterone-sulfate ([H]-DHEA-S) was injected intraamniotically. Maternal venous blood was drawn before and at regular intervals for 240 minutes after DHEA-injection. Thereafter, legal abortion was performed by intraamniotic instillation of prostaglandine. The conjugated steroids were hydrolyzed enzymatically and the total steroids were isolated and identified. The following labelled metabolites were determined quantitatively: Estriol (e3, estradiol-17beta (E2-17beta), estrone(E1), 16alpha-hydroxy-estrone, (16alpha-OH-DHEA), ALPHA4-androstenedione (AD) and testosterone (T). The maximal increase of all estrogen fractions in matermal plasma occurred 120-180min after intraamniotic injection of the precursor. The most prominent rise of the C18-steroids could be shown for estriol. 60-70% of all metabolites were C16-hydroxylated.


Simultaneous high-pressure liquid chromatographic determination of niacin and niacinamide in multivitamin preparations: reversed-phase, ion-pairing approach. A high-pressure liquid chromatographic procedure for the simultaneous determination of niacin and niacinamide in multivitamin preparations was developed and evaluated. Reversed-phase liquid chromatography with dioctyl sodium sulfosuccinate in the mobile phase is utilized for the analysis. The accuracy and precision of the procedure were compared with those of the currently official procedure.


[Comments on the accessory tubercle of the lumbar costiform apophysis (author's transl)]. The first results of a study of Luschka's accessory tubercle and Broca's styloid hypophysis, and especially of osteotendinitis which can arise from musculo-tendinous fatigue in this zone insertion. This osteotendinitis, whose radiological demonstration is difficult and rarely done, can possibly explain undoubtedly certain cases of localized lumbago.


Diagnostic and preventive services in a national incremental dental plan for children. A modelling exercise was carried out to examine the potential expenditure in a national incremental dental program for children aged six to 13. Using Relative Value Units (RVUs) as a proxy for dollars, the relative expenditures for care per child in fluoridated and fluoride-deficient areas were assessed. Dental treatment requirements were taken from existing data as far as possible. Arrangements for the delivery of care were based on existing pocicies of the American Dental Association, an services delivered were based on the recommendations of the American Academy of Pedodontics and the American Society of Dentistry for Children. Orthodontic care was limited to space maintainers and simple interceptive care. Children were assumed to receive initial care at age six, and annual maintenance care from ages seven to 13. The results showed that although restorative care would be 49.8 percent less expensive for children in fluoridated areas, total care would be only 11.9 percent less expensive. The major reason for this difference was the high proportion of annual maintenance-care costs that would be absorbed by diagnostic and preventive services using UCR fees. The necessity for much of this care is questioned under the conditions of this model, and some methods by which the dental profession might control the relatively high cost of diagnostic-preventive services are suggested.


The prevalence of Huntington's chorea in an area of East Anglia. The prevalence of Huntington's chorea in East Anglia was sought by following up a series of different sources, both in hospitals and in the community. The results show that the prevalence of the disease in this area is very much higher than has previously been reported and is comparable to the highest rates known anywhere in the world.


Evaluation of the fallopian tube section obtained at laparoscopic fulguration. Three hundred tubal specimens obtained at laparoscopic coagulation and resection of the tube for sterilization done in the years 1973 and 1974 were studied. Twenty-three percent of the specimens were not identifiable as of tubal origin, and there was a lack of precision in the diagnosis in 17% of the specimens. Because of the comparable results for sterilization by well-performed coagulation alone and of coagulation with resection of a segment of tube, we feel that resection, with its assocaited hazards, is unnecessary.


Outpatient laparoscopic sterilization: a review of complications in 2,000 cases. After reviewing the surgical reports of 2,000 female sterilizations by laparoscopy done in a one-year period we found a total incidence of operative complications of 3.9%. Hemorrhage was the most frequent complication (2%). There was a low incidence of bowel burns (0.15%).


Documents and documentation in laparoscopy. Some form of documentation of laparoscopic findings is essential in the proper management of the patient. We have found a simple outline form with a schematic drawing of the pelvis to be invaluable in emphasizing the need for a systematic and thorough endoscopic examination and in providing an excellent method of recall. Photographic documentation is primarily of value to those physicians involved in research or educational programs. In addition, we have found it helpful to give the patients a printed description of the procedure beforehand, as well as written instructions concerning preoperative arrangements and postoperative care.


Studies on anticoccidial agents. 10. Synthesis and anticoccidial activity of 5-nitronicotinamide and its analogues. 5-Nitronicotinamide (1) was prepared from 5-bromonicotinoyl chloride by treatment with ammonia and then oxidation with fuming H2SO4 and 30% H202. 2-Cholor-, 2-alkoxy-2-benzyloxy,2-phenoxy-,2-alkylamino-, and 2-benzylamino-5-nitronicatinamides were also prepared via 2-chloro-3-cyano-5-nitropyridine. 2-Methyl-5-nitronicotinamide (2) was obtained from ethyl 2-methyl-5-nitronicotinate by treatment with ammonia; the 4-methyl analogue 3 was from 3-cyano-2,6-dihydroxy-4 methylpyridine by nitration, chlorination, and dechlorination, and the 6-methyl analogue 4 was prepared by transforming 2-chloro-3-cyano-6-methyl-5-nitropyridine to the corresponding amide, followed by dechlorination. Of these compounds, the 5-nitronicotinamide, the 2-methyl and 4-methyl but not the 6-methyl, analogue showed significant anticoccidial activity against eimeria tenella. N-Substituted analogues of 5-nitronicotinamide and 2-methyl-5-nitronicotinamide were prepared in a conventional manner and optimal anticoccidial activity was attained with their lower N-alkyl analogues, N-alkanoyl and -alkenoyl analogues, and N-aromatic acyl analogues together with these parent compounds.


Antifolate studies. Activities of 40 potential antimalarial compounds against sensitive and chlorguanide triazine resistant strains of folate-requiring bacteria and Escherichia coli. As part of the search for new antimalarial drugs, a screening program was developed using sensitive and chlorguanide triazine (CGT, cycloguanil) resistant strains of the folate-requiring bacteria, Streptococcus faecium durans, Lactobacillus casei, and Pediococcus cerevisiae. The activities of 40 compounds have been studied against these strains and Escherichia coli. Observations have been made on the points of 50% growth inhibition, the fold increase of resistance shown to each compound by the resistant strains as compared with the parent sensitive strains, and the reversal of growth inhibition by folic acid with S. faecium and L. casei by folinic acid with P. cerevisiae and by p-aminobenzoic acid with E. coli. Comparisons have been made of the activities of the test compounds with those of the standard antimalarial antifoltes, CGT and pyrimethamine (PM), and the antibacterial results have been compared with the activities of the compounds against Plasmodium berghei infections in the mouse and against human malaria infections where data are available. Of the 17 compounds reversed by folates, five had patterns of activity similar to CGT and PM in that they were most active against S. faecium and nine compounds exhibited a different pattern, being highly active against all four test bacteria. This suggests that these latter compounds either have different pharmacokinetic properties or have additional modes of action. The three CGT-resistant organisms responded to antifolates in different ways. S. faecium (R) and P. cerevisiae (R) strains were cross resistant to 4,6-diaminotriazines, 2,4-diaminopyrimidines, 2,4-diaminoquinazolines, and active 2,4-diaminopteridines. L. casei (R) was cross resistant to the triazines but was collaterally sensitive to all the other antifolates. Most of the compounds not reversed by folates were much less inhibitory for the test organisms; they were most active against L. casei. In general, their growth inhibitory concentrations varied less for the four test organisms and the responses of the sensitive and CGTR strains were similar. However, there was some cross resistance to five compounds and some collateral sensitivity to five others. Comparison of the bacteriological data with the activities of the compounds against Plasmodium berghei in the mouse showed little correlation between the two test systems; each appears to provide independent and useful information.


A case of gouty arthritis associated with Down's syndrome. Gouty arthritis developed in a twenty-one-year-old male whose karyotyping showed Trisomy 21. His serum urate level was 13.1 mg per 100 ml and his twenty-four-hour urinary uric acid excretion was 431 mg on a low purine diet. Uric acid clearance was decreased to 3.9 ml per minute. The cumulative incorporation of N15-glycine  into urinary uric acid during successive seven days was 0.144 per cent, which was within the normal range. Diminished uric acid clearance may be attributed to this hyperuricaemia. The cause of gouty arthritis and Down's syndrome in the patient is discussed.


Use of aspartame by apparently healthy children and adolescents. This study was conducted to determine the effects and the differences, if any, resulting from the ingestion of aspartame (sweetener) versus sucrose. A 13-wk, double-blind study was conducted using 126 apparently healthy children and adolescents as panelists. Individuals were randomly assigned in a double-blind design to aspartame or sucrose in each of five age groups; dosage levels were assigned according to age and weight groups. Physical examinations and special eye examinations were performed at the beginning and end of the study. Other parameters determined including laboratory tests of liver and renal function, hematologic status, and plasma levels of phenylalanine and tyrosine. Clinically significant differences in laboratory parameters measured could not be demonstrated; all mean values were within normal limits. No unusual findings were observed in phenylalanine or tyrosine levels. All phenylpyruvic acid and methanol determinations were negative. No important physical changes occurred, and no product-related side effects were reported.


[The urethra in congenital aplasia of the abdominal wall. Concerning 15 cases (author's transl)]. The authors have collected in 13 years, 15 cases of congenital aplasia of the abdominal wall. All of the patients had involvement of the urinary apparatus of varying degree of severity, megalo-ureter, megabladder and dilatation of the posterior urethra being the most constant lesions. Twelve patients with renal failure, benefited from reparatory surgery of the excretory pathway. Eleven patients had complete or incomplete retention: in 5 cases there was a urethral valve. In 6 cases the megalo-urethra was apparently idiopathic. In all of these cases, endoscopic treatment was carried out, constituted either of resection of valves, or internal urethro-sphincterotomy using a cutting electrode: 9 times, the result obtained was excellent. One patient was improved; in one case the result could not be assessed. For the authors, obstructive urethral pathology is a frequently unrecognized or badly understood fact. It is accessible to endoscopic treatment, which must precede or accompany correction of the ureteral abnormalities.


SP-10 bacteriophage-specific nucleic acid and enzyme synthesis in Bacillus subtilis W23. Bacillus subtilis W23 was infected with a clear-plaque variant of SP-10 phage, namely, SP-10c. Exogenous thymidine was not incorporated into phage DNA (even in the presence of deoxyadenosine), nor was there any transfer of thymidine nucleotides from bacterial to viral DNA. The lytic program was unaffected by concentrations of 5-fluorodeoxyuridine sufficient to reduce bacterial DNA synthesis by greater than 95%. Although these data are consistent with the interpretation that thymidine nucleotides are excluded from phage DNA, formic acid digests of SP-10c DNA contained what appeared to be the four conventional bases; however, adenine and thymine were not recovered in equimolar yields. DNA-RNA hybridization and hybridization competition experiments were done. Synthesis of host RNA started to wane moments postinfection and stopped completely by 36 min. SP-10c coded for discrete classes of early and late RNA. The possibility of discrete subclasses of early RNA exists. Replication of the bacterial genome appeared to terminate 12 min postinfection. Degradation of the host DNA to acid-soluble material started at 36 min and, by the end of the latent period, greater than 90% of the host chromosome was hydrolyzed. Four apparent phage-coded enzymes have been identified. A di- and triphosphatase degraded dUTP, dUDP, dTTP, and dTDP (and, to a lesser extent, dCDP and d CTP) to the corresponding monophosphates; the enzyme had no apparent activity on dATP and dGTP. SP10c also coded for a DNA-dependent DNA polymerase, lysozyme, and a nuclease that degrades native bacterial DNA. Judging from the dependence of enzyme synthesis on the time of addition of rifampin (an inhibitor of the initiation of RNA synthesis), messengers for the di- and triphosphatase, as well as the nuclease, are transcribed from promoters that start to function 6 min postinfection. Promoters for polymerase and lysozyme did not become functional until 8 and 16 min postinfection, respectively.


Breast cancer induced by radiation. Relation to mammography and treatment of acne. This communication reports cases of 16 women in who cancer of the breast developed after radiation therapy for acne or hirsutism, suggesting another group at higher risk than is generally expected for cancer of the breast. It is prudent to regard the carcinogenic effect of radiation on the breast as proportional to dose without a threshold. Mammography in young women should be ordered only selectively, not for screening.


[Protective effect of schizophyllan on Pseudomonas aeruginosa infection of mouse (author's transl)]. Effects of schizophyllan (SPG) and several antibiotics in combination against experimental Pseudomonas aeruginosa infection were examined. (1) Whereas the increase in protective effect of SPG was not observed in combination with carbenicillin or sulbenicillin, remarkable effects could be recognized in combination with dibekacin or gentamicin (GM). The combined therapy with SPG and GM proved to be most excellent. (2) The time course for changes of viable number of Ps. aeruginosa in various organs of mice revealed that the multiplication of the infected bacteria was more markedly inhibited in mice treated with SPG and GM in combination than those treated with each alone. (3) The increase in bactericidal activity of the peritoneal exudate cells was more remarkably demonstrated in the combined treatment with SPG and GM than with each alone, showing the rapid clearance of bacteria from the peritoneal cavity in the former. (4) The microscopic estimation demonstrated that the increase in both phagocytic index and intracellular digestion of bacteria by cultivated macrophages was larger in combination of SPG and GM than each alone. (5) The measurement of viable number of bacteria in cultivated macrophages by the plate-count method also showed that the ingestion and bactericidal activity within the cells were much higher in combined treatment with SPG and GM than each alone.


Visual examination for blunt abdominal trauma. Visualization of the peritoneal cavity to determine the presence of free blood is desirable to diagnose the condition of a patient who has suffered blunt abdominal trauma. Four-quadrant tap plus peritoneal lavage is reliable but the irrigant fluid may return only slightly pink or not return at all. In the Kansas University Medical Center emergency department, 26 Needlescopic examinations have been tried, with 92% accuracy and two false positive results. The Needlescope procedure is described.


Knuckle pads, leukonychia, deafness, and keratosis palmoplantaris: report of a family. A family is described in which knuckle pads, leukonychia, deafness, and keratosis palmoplantaris are present as a syndrome is several members. This is the second such family reported demonstrating that keratosis palmoplantaris is part of the syndrome. Inheritance pattern is probably autosomal dominant.


[Status of physical environmental factors and the frequency of the chief complications of acute myocardial infarct]. While studying the course of the disease in 2143 patients with macrofocal myocardial infarction it was found that with significant departure from mean for the city of Leningrad values of relative air humidity, intensity of terrestrial magnetism and differentials of atmospheric pressure the incidence of major complications of the disease is on the increase. An analysis of pertinent data leads to the conclusion on the need of arranging trial-tests to verify the effect on the course of acute myocardial infarction of the patient's stay in a specially equipped ward, where the parameters of the physical environmental factors are maintained at levels mean for a given locality.


[Pathogenesis of cardiac insufficiency in thyrotoxicosis]. The purpose of the work was to study some problems relating to the pathogenesis of cardiac insufficiency in patients with thyrotoxicosis. To do this a total of 108 patients suffering from thyrotoxicosis with varying degree of severity and aged from 17 to 59 were examined. In addition to the general clinical examination vectoro-, poly- and mechanocardiography was employed. The resulting findings ascertained two possible ways for the development of cardiac insufficiency in patients under consideration. One of them is cardiac hyperfunction that comes to the forefront. In this case the myocardial changes are of a stage-wise nature. The myocardial contractility at the onset of the affection is up, a slight hypertrophy is developing, chiefly, of the outflow passages. As the disease progresses further hypertrophy gains in intensity and dilation of the heart comes in as an intercurrent factor. At this time the contractile function of the myocardium is still unaffected and the patients are at a stage of compensation. With progressing dystrophy and wearing away of the myocardium its contractility is declining and signs of cardiac incompetence appear. Such a development is characteristic of patients with severe course of thyrotoxicosis, long-standing disease and frequent relapses. Of the other way is typical cardiac hyperfunction of low intensity. To the forefront come dystrophic alterations in the myocardium unaccompanied by hypertrophy, and in this case cardiac insufficiency is of latent nature. Such alterations are seen to occur with a milder course of thyrotoxicosis, with the disease of short duration. Dynamic observations bear proof to a reversible nature of hypertrophy and dystrophy of the myocardium.


[Insufficiency of the hypertrophied heart]. The mechanism limiting the function of a normal heart is considered and the key part played in it by the system of an active ionic transport of the myocardial cell is pointed out. With an excessive load on the heart and also in cases of hypoxic and other lesions of the heart muscle--the mechanism limiting the cardiac function becomes the main causative factor of cardiac insufficiency.


[Cardiac insufficiency and its morphological expression]. The paper sets forth materials reflecting the present-day views of morphologists concerning the problem of cardiac insufficiency. The current state of the problem relating to morphology of the myocardium in cardiac incompetence is characterized. It is suggested that cardiac incompetence cannot be approached as a unique issue, and in different affections the pathogenesis of the heart muscle debility may prove to be dissimilar. Ultrastructural changes in the left heart myocardium of the rabbit, at a distance from the ischemic area, in experimental myocardial infarction at the stage of compensatory hypertrophy and with developing acute cardiac incompetence are described. In the lastly named case the mitochondria of myocites were found to contain compact bodies, apparently made up of calcium phosphate. Their appearance comes as a proof of irreversibility of the supervened changes.


[Diagnostic characteristics of cardiac insufficiency under mountain conditions]. In patients with mitral lesions and prevalence of stenosis and insufficient circulation of the I, II A and B stages clinical and functional indicators of the cardiac work were studied at three different altitudes, viz. with a low-mountain relief (760 m), middle-mountain relief (1650-2020 m) and in highland (3600-4200 m). In highland decompensated mitral incompetence was found to be characterized by a much higher incidence of such manifestations of the disease as vertigo, syncopal attacks, fits of distressed respiration, epigastral pulsation, positive venous pulse, a significant expansion of the heart to the right, accentuation and splitting of the II tone on the pulmonary artery, overloading of the right ventricle and atrium (according to ECG findings), the absence of peripheral edematization and fibrillation arrythmia, the presence of arterial and venous hypotension, highly intensive hyperventilation, a drop of PAO2 and PACO2. In patients-residents of low- and middle-mountain regions the severity of clinical and hemodynamic disorders depended on the stage of cardiac insufficiency, whereby in residents of the second region the disclosed deviations on the level of circulation proved more marked. It is shown that the correlation links between individual physiological variables become greatly disrupted parallel with progressively increasing severity of cardiac incompetence. In conditions prevailing in the middle and, especially, high altitude areas there are evident links between individual functional indicators which are absent in low-mountain areas. The above data bear evidence not only to the fact that with progressive severity of cardiac insufficiency the disrupted regulation of the circulation system becomes still more aggravated, but also to the presence of other compensatory mechanisms that are operative in mountain areas.


[Function of the sodium-potassium pump and its corticosteroid regulation as factors limiting cardiac adaptation to severe physical exertion]. Experiments were carried out on male Wistar rats in order to clarify the leading biochemical mechanism responsible for an increase in the functional capacity of the heart. The obtained results indicate that the function of the Na,K-pump in myocardial sarcolemma is rather stable and deteriorates only during extreme exertion. The alteration of the Na,K-pump function due to a decrease in Na,K-ATP-ase activity leads to a decrease in the Na gradient and an accumulation of water in the cells which in turn reduces the capacity of the Na-Ca exchange mechanism and the rate of Ca removal from the myofibrils. Hence, the decrease in the working capacity of the heart during excessive physical exercises is primarily connected with the exhaustion of the ions active transport mechanism rather than the mechanism of aerobic energy production. In accordance with this conclusion, the functional stability of the myocardial Na,K-pump increased in our experiments with regular training, whereas the capacity to regenerate ATP via oxidative phosphorylation did not change, as demonstrated by Holloszy et al. Experiments in adrenalectomized animals, with or without administration of gluco- and mineralocorticoids, has revealed that an adequate supply of glucocorticoids to the heart is important in maintaining the function of the myocardial Na,K-pump and thereby in the working capacity of the heart during severe physical exertion.


[High-altitude pulmonary hypertension and fibrinolysis]. The fibrinolytic system of the blood was studied in 49 indigenous residents at an altitude of 3600 m above sea level having signs of altitude pulmonary hypertension, and in 48 persons without such signs. The control group comprised 70 residents of Dushanbe (810 m above sea level). Persons with altitude pulmonary hypertension were found to have an increased fibrinolytic activity, a reduced content of antiplasmins and inhibitors of plasminogen activation. These changes are combined with a reduction of the fibrinogen content and a decrease in the activity of the fibrin-stabilizing factor. No principal difference was found in the fibrinolytic system of comparable groups having signs of altitude pulmonary hypertension, and without such signs.


[Influence of temperature on shear induced platelet aggregation in vitro (author's transl)]. The extent of platelet aggregation (PA) in vitro was investigated in relation to the temperature. The measurements were performed with a newly developed device in which PA is induced by a well-defined viscometric flow without addition of specific aggregation promoting agents. It was found that the PA occurs in two phases as related to temperature: at 4 degrees C and 37 degrees C there is none and a minimal PA respectively, whereas at room temperature strong PA takes place. It is proposed that these results indicate that both physicochemical mechanisms and the availability of metabolic energy linked with activation of contractile processes are prerequisites for platelet aggregation. The clinical aspects are discussed.


[Tolerance for hypokinesia in persons adapted to high mountains]. After a 26-day exposure to an altitude of 3200 m test subjects were kept in bed for 10 and 24 days. Each experimental group consisted of 6 test subjects. Physiological effects  of the exposure were measured with respect to changes in the respiration, circulation and red blood systems as well as in the orthostatic and exercise tolerance. High altitude adaptation which preceded bed rest did not arrest the development of orthostatic intolerance or the decrease of physical performance that resulted from the bed rest experiment.


[Clinical course of a radiation lesion under high-mountain conditions]. The development and outcome of radiation disease were studied on dogs kept at an altitude of 3200 m above sea level. Clinical observations, morphological examinations of blood and bone marrow and measurements of blood coagulation parameters were carried out at different time intervals. Our findings demonstrated that irradiation of animals that followed a 25-day altitude acclimatization and their subsequent exposure to an altitude alleviated radiation disease. The clinical course of radiation disease aggravated in dogs that were reacclimatized to highlands after irradiation. It can be postulated that the dogs kept in highlands before and after irradiation developed a more intensive process of restoration, especially of erythropoiesis. They also showed a stable decrease of the blood coagulation rate and long persistence of high fibrinolytic activity of the blood.


[The activity and capacity of the inner ear (author's transl)]. The inner ear is an energy converter and a biochemical amplifier. The normal function of the stria vascularis and the organ of Corti is bound exclusively to the respiratory metabolism. Some but not all species are equiped by a glycolytic reserve metabolism for preservation of the sensory cells, as could be improved in amplitude-time-curves of cochlea microphonics in hypoxic conditiones. A promising therapy of inner ear disturbances following short timed oxygen deficiency depends on the moment of the treatment.


[Middle ear deafness and noise trauma. Animal studies with the surface specimen technique (author's transl)]. The pertinent clinical literature concerning the research project is reviewed. The middle ear of guinea pigs was first damaged on one side (inflicting a subtotal perforation of the tympanic membrane, dislocation of the incudo-stapedial joint followed by otitis media) and the animals were then exposed to a specified narrow-band noise. The induced inner ear changes were quantified by means of cochleographic studies using the surface specimen technique. In spite of the inner ear changes due to middle ear manipulation prior to the noise exposure, the cochleographic studies revealed an obvious protective effect of the induced middle ear changes upon the inner ear during noise exposure.


[ENG in infants - a contribution on examination problems (author's transl)]. 60 young children (3-6 years old) without any history of ear diseases were tested by caloric stimulation (30 degrees C and 44 degrees C). Distribution into the groups "with sedation" and "without sedation" was done following a statistical key. Sedation was achieved by intramusculair injection of Valium, considering age and weight of the subjects. Nystagmus registration was done by ENG. The following quantitative reductions in the observed nystagmus parameters could be shown: number of beats: 19% +/- 5%, maximal angular velocity of the slow phase: 24% +/- 11%, total amplitude: 24% +/- 11%. This experiment shows that Valium can be very well used in the sedation of young children for caloric vestibular testing, a quantitative variation of the response has to be considered.


[The capacity to destinguish changes in the intensity as a function of volume and frequency (author's transl)]. Békésy audiometry equipment was used for investigations carried out in 15 test persons to study the intensity differentiation threshold. We tried to find the degree of intensity required to recognize given dB changes in the intensity. The results achieved very well coincide with those established by other authors. It was possible to statistically prove the volume dependence of the intensity differentiation threshold, it was, however, not possible to establish any frequency dependence. The relations of our result with the SISI test are under discussion.


[Goblet cells in nasal allergy (author's transl)]. After staining of the whole nasal mucosa from a patient with nasal allergy by the PAS-alcian-blue whole mount method, the density of goblet cells was determined quantitatively. In most sections of the nasal septum and of the inferior and middle nasal concha, the density of goblet cells was found to be considerably lower than in normal subjects. While in some sections, in particular posteriorly, the density was the same as in normal subjects, it was nowhere higher. The low density may be due to metaplastic changes of the epithelium which had thickened and lost ciliary cells. Previous statements that the density of goblet cells is increased in nasal allergy could not be confirmed quantitatively, but investigation of larger materials is called for before any conclusions may be drawn.


[The isoenzyme pattern of lactate-dehydrogenase in nasal secretions (author's transl)]. In the present study, the qualitative and quantitative isoenzyme pattern of lactate-dehydrogenase (LDH) in nasal secretions of 52 probands without disease in the nose is investigated electrophoretically. It was found that the LDH-isoenzyme pattern in nasal secretions does not only differ clearly from the distribution of LDH-isoenzymes is serum of the same probands but is characterized especially by a high percentage of LDH 3- and LDH 4-fractions; this corresponds to the monomeres H2M2 and HM3. These results differ completely from any other enzymatic pattern in the human organism. The results clearly indicate that LDH in nasal secretion is a product of the mucous membranes and does not originate from the serum by means of transsudation into the nasal secretion.


[A clinical method of testing the humidifying capicity of the human nose (author's transl)]. At the beginning attention is drawn to the fact that there is a lack of suitable clinical tests for the measurement of the humidifying and warming capacity of the nose. The great number of testing methods which have been published so far, have been either too complicated to be applied in routine checks or they were too physically strenous, so that this could not be reasonably demanded of the patients. With the help of the clinical method of testing introduced by us one can find out about norm data for the quantitiy of water needed for humidifying the inspired air in healthy persons, as well as examine the influence of pharmacons on the secretion capacity of the nose. In addition to this, pathological states such as atrophic rhinitis, vasomotoric and allergic rhinitis, patients operated with a partial maxillectomy or with total laryngectomy can also be tested as far as the humidifying and warming capacity of the nose ist concerned. In our testing method extremely dry air streams out of a compressed air cylinder with a flow of 8 1/min through a small silicone catheter at the choanal end of one nasal part and is sucked out of the other nostril with a suction flow of 5 1/min, the air passing through a psychrometer modified by us. The excess flow of 3 1/min streams from the naso- into the oropharynx most effectively preventing the air which is to be measured from mixing with the expiratory air saturated with water-vapor. A gas analyzer sensitive to carbon dioxide measures the error possible in this open system which amounts to only one percent of an average mixture with expiratory air. With the help of a psychrometer-normogramme the absolute humidity is determined from the data of the wet and both the dry thermometers. We were testing 22 healthy persons, average age 34, the norm data were established. The result is that for the hole 10 minute measurement period one nasal part needs 1.58 g water for the humidifying of the inspired air. From this it can be calculated that 456 g of water are necessary for humidifying the inspired air through both nasal parts during 24 hours. Compared with other exact methods, which, however, are not suitable for clinical tests (Ingelstedt et al.) our simple and easily workable method correlate very well.


[Cytostatic therapy in oto-rhino-laryngology (author's transl)]. The report covers the therapeutic results achieved after using cytostatic drugs in 104 patients treated at the 1st Oto-Rhino-Laryngological Univ. Hospital, Vienna, between 1967 and 1975. The breakdown according to the tumor histology shows that squamous cell carcinomas accounted for the highest per centage, i.e. 53%; laryngeal tumor prevails according to the tumor localization. In 42 patients it was not possible to positively influence the disease; 45 patients showed a disruption or a slowdown of the progress of the disease; in 17 patients all measurable criteria of the disease receded (classification according to Karnofsky). Even if the average survival time after the commencement of the therapy amounted to only about 6 months, it was nevertheless possible to positively influence the progress of the disease by means of cytosatic therapy.


[Parameters of OEMG for Judgement of Facial Function (author's transl)]. In order to test the function of facial nerve in Bells palsy we used three methods, the function test of Schubert-Cobet, the nerve excitability test and the surface electromyography. We could find a correlation in the parameters of this methods in judgement of facial nerve function.


[A survey about findings and courses of 300 facial palsies. A correlation of clinical and electrophysiological findings on computer (author's transl)]. A survey on 288 facial palsies in the years 1973 to 1975 is given. On a small computer (IBM 1800 was made a correlation of refined anamnesis and elaborate diagnostic findings. Nerve Excitability Test (NET) and Maximal Stimulation Test (MST) were mainly taken into account. The value of MST (i.E. Electroneuronography) for early prognosis of facial palsy is pointed out.


[Otological symptoms due to disturbances of the major extracranial arteries (author's transl)]. 127 patients with pulseless disease were compared with normal persons of the same age group, localization and distribution of the occlusions, risk factors and complaints were analysed. Pulseless disease occurs predominantly in elderly men. In all patients, occlusions were found more often in the left supraaortic branches than in the right side. In men, stenosis of the left subclavian artery, in women stenosis of the right carotid artery is found most frequently. In most cases only one aortic branch was diseased. Vertigo, tinnitus and deafness was encountered in 32 patients (25.20%) but only in 3 persons of the control group (2.36%). In 29 of these 32 patients uni- or bilateral stenosis of the carotid artery was present. In the cases with unilateral stenosis (16) tinnitus and deafness could be localized to the respective side. In the other cases an isolated stenosis of the subclavian artery was found. In the 32 patients with otogenic symptoms hypertension was the risk factor number 1. Early diagnosis by only auscultation and palpation as well as medical treatment is pointed out.


[SISI or differential limen test - tests for recruitment (author's transl)]. The detection of recruitment is based on investigating change of loudness with change of intensity. The evaluation and further differential diagnosis of inner ear damage is, for instance, a necessity in an expert opinion of an ENT specialist. Which of the numerous methods of detecting recruitment can be recommended for the specialists practice. Over 215 patients with inner ear damage were tested for recruitment with different test methods. Results showed that SISI tests were performed with more accuracy than differential limen tests. Differences of various recruitment methods of our collective are investigated and advantages and disadvantages discussed. The recommendation for the specialists practice would be to perform 1. the "limits of intensity" (threshold of hearing and loudness discomfort), 2. the supraliminal noise-audiometry Langenbeck and 3. the SISI test. They seem to be most effectful, exact, reproducible and easy to perform test-methods for detecting recruitment.


[Superselective angiographic finding in a case of osteom of the skull and the therapeutic consequences (author's transl)]. The informational value and therapeutic application of the selective angiography is demonstrated in an osteoma fronto-temporo-parietal. The vessels feeding the tumor were identified and an artificial embolisation was performed.


[Hearing loss by ossified stapedius tendons (author's transl)]. As rare cause of a conductive impairment of 10 to 30 dB ossified stapedius tendons were found. After cutting the tendons the hearing was normal.


[Mineral oil pneumonia caused by throat gargles containing lipoid paraffin. Diagnosed by biochemical examination of the sputum (author's transl)]. A 20-year-old man developed a pneumonia after using throat gargles containing lipoid paraffin over 5 years. The lung biopsy showed a lipoid pneumonia and the bodyplethysmographic examination a ventilation disorder indicating a starting lung fibrosis. By the means of gaschromatography the identity of the lipoid in the sputum and in the gargle sample was established and the diagnosis continued. The disease, its pathophysiology and iatrogenic etiology are discussed and the consequencies concerning the ENT-specialist are stressed.


[Hematogenous metastases of benign pleomorphic adenomas of the salivary glands (author's transl)]. Hematogenous metastases of benign pleomorphic adenomas are exceptionally rare. In three secure reports of the world literature metastases occurred in lung, liver or bone after operation of a benign pleomorphic adenoma with the greatest interval of twenty-two years between operation and metastases. This will be interpreted as implantation-metastases. All other observations represented secondary carcinomas in pre-existing pleomorphic adenomas. The morphological criterias of an accurate classification are explained. A number of reports of the literature about metastases of benign pleomorphic adenomas deals with misinterpretations of secondary adenomas in pre-existing pleomorphic adenomas.


[Pseudotumor of the parotid gland as a result of dilatation of the Stenon's duct (author's transl)]. A unilateral dilatation of the parotid duct of Stenon (parotis emphysema, pneumatocele) was observed in a 73-year-old patient. The possible course of development - inflammatory or other known factors excluded - for example by means of leucoceratosis nicotina palati are discussed.


[Damage of the cochlea and of the cochlear nucleus after the application of aminoglycosid antibiotics--a comparative light-, transmission- and scanning electronmicroscopic study in the guinea pig (author's transl)]. Ototoxic alterations were studied in the guinea pig organ of Corti and in the cochlear nucleus after high administrations of aminoglycosid antibiotics (Gentamicin/Tobramycin, 150 mg/kg body weight/day or Amikacin 300 mg/kg body weight for 10 days). After survival times up to 22 days the animals were examined. By means of morphology degeneration was found in the cochlear nucleus before we could state it in the organ of Corti. After longer survival times, when we observed heavy degeneration in the organ of Corti we found only a few myelin figures of axons in the cochlear nerve. Cochlear nucleus: As an early sign of degeneration alterations in the mitochondria were found. Compared with the organ of Corti the damage was less widespread in the second order neurons of the afferent auditory pathways, their dendrites or nerve endings. Quantitative calculations however, were not performed. In axosomatic synapses we could observe a way of degeneration which was not reported before in damage caused by aminoglycosid antibiotics. Free postsynaptic densities were observed to be invaginated into the neuron as a probable way of sequestration. As well we could observe reoccupation of the synaptic sites by a probable sliding of neighbouring nerve endings into the free intracellular space. (Similar observations were reported first by Gentschev and Sotelo [1973] after ablation of the cochlear nerve in rats.


[Ultrastructural study of the chorda tympani nerve in man (author's transl)]. Chorda tympani nerve specimens of 10 patients were studied by the light and electron microscope. The nerve specimens were obtained while performing stapedectomy in 7 patients, a tympanoplasty in two patients with otitis media chronica, and from one patient whodied 8 months after hemiglossectomy, neck-dissection and radiotherapy because of squamous cell carcinoma. The chorda tympani nerve is built up by few 10 to 12 micron thick and numerous 3 to 4 micron thick myelinated fibers in the semithick sections. The 10 to 12 micron axons are largely reduced in patients with chronic middle ear infection and in older patients. In persons with otosclerosis degenerative alterations of the axons and inclusions in the cytoplasm of the Schwann cells can be demonstrated similar to those of the diabetic, alcohol induced and ischemic neuropathy. In patients with chronic middle ear disease the degenerative changes mainly occur in the myelin sheats and in axoplasma finally leading to axolysis. A total degeneration and fibrous transformation of the chorda tympani nerve can be observed after hemiglossectomy. By means of morphological criteria afferent and efferent axons can not be distinguished in this material.


[Otosclerosis involving the capsule and inner ear. Morphological findings (author's transl)]. The problem of otosclerotic inner ear damage is considered on the basis of morphological findings. It is pointed out that the disease of the otic capsule certainly also affects the underlying sense organ. This arises through disturbance of the perilymphatic electrolytes, venous stasis and thus changes in the circulation, disturbed regulation of endolymph and, more rarely, the direct effect of the focus on the auditory nerve or calcification of the mobile membranes.


[Facial palsy and leontiasis ossea of the pyramid (author's transl)]. The author presents a boy which has repeated facial palsies since his second year of life. The clinical examination showed: conduction deafness, radiological sclerosis of the bones of the basis of the skull, normal values of chemical blood analysis. Both facial nerves are operated in the mastoid and middle ear portions. The histological examination of the mastoid bone reveals a leontiasis ossea. The histological structure of the bone are described in detail and the differential diagnosis with other bone diseases of the cranial bones is discussed.


[Clinical and experimental examination of the resorption capacity of the tympanic cavity mucosa (author's transl)]. In a clinical examination of 25 patients with a mesotympanic perforation of the ear drum, it was found after the administration of 35 mg pilocarpine hydrochloride in water or in agar gel into the tympanic cavity, that the mucous membrane of the middle ear complex possesses a significant resorption capacity. The salivation curves obtained in these tests displayed exactly the same characteristics as the curves obtained after administration of the same amount of pilocarpine to the nasal and tracheal mucosa. The results of mathematical processing of the salivation curves by computer (Hawlett-Packard 30) are also given in the study.


[Impairment of hearing in a case of osteogenesis imperfecta tarda (author's transl)]. Report on a case of Osteogenesis imperfecta tarda with a "van der Hoeve-syndrome", where the impairment of hearing could be restored by Stapesplastic by Schuknecht. For the first time it was possible to prove the Osteogenesis imperfecta tarda by means of histological sections of the extracted stapes.


[The collapse of the alae and inner valve of the nose (author's transl)]. The collapse of the alae and inner valve is caused more frequently be regressive changes of the aging tissues then by congenital weakness of the cartilaginous structures. Years ago we have published an operative method for the rehabilitation of this kind of nasal dysfunction. Now we have simplified our method and do not use any longer incisions in the vestibule of nose.


[Damages of the auditory pathway at brain stem level investigated by acoustically evoked potentials (author's transl)]. In 57 patients with operated expansive tumors in the postcranial fossa auditory evoked brain stem potentials were investigated. A group of 36 with neurological evidence for the brain stem compression showed significantly prolonged latencies (Fig. 1), whereas the evoked potentials were nearly normal in the preceding state of CSF circulatory disturbances (21 cases). For one patient with a neurinoma of the right trigeminal root the post-operative reduction of the pathological latency shift is demonstrated (Fig. 2). Latency evaluation of evoked brain stem potentials are used in our clinical routine for differential diagnosis of retrocochlear hearing damages.


[Evoked response audiometry and vestibular examinations in patients with multiple sclerosis (author's transl)]. A possible involvement of the VIII cranial nerve in Multiple Sklerosis was investigated. 15 of the 135 MS-patients were tested by evoked response audiometry (ERA) and vestibular examinations. Only a central nystagmus, central vertigo and coordination disorder were seen. Lesions of the peripheral vestibular system and pathological data of the evoked response audiometry were not found.


[Surgical elimination of endonasal triggerpoints of a trigeminal neuralgia caused by cauterization (author's transl)]. A severe injury by fluid Ammonia of the nasal mucosa resulted with a strong irritation of the 1. and 2. branch of the trigeminus nerve with sudden and heavy attacks of pain. The region below the head of the right inferior nasal concha was detected as a trigger zone for smoke, smell, dust and cold air. Local anaesthesia stopped the attacks. The surgical excision and electrocoagulation of that aerea and the lateropexis of the inferior concha avoided the returning of the troubles for over a half year. The recommencement of the attacks could be stopped by local application of carbolic acid solution (10%). A similar treatment could not be found in the literature.


[Equilibrium troubles with cervical syndrome and their relation with otorhinolaryngology (author's transl)]. The equilibrium troubles occuring in connection with cervical locomotoric diseases and their otorhino-laryngologic relations have been studied in the ORL Department of National Institute of Rheumatism and Medical Hydrology. It has been found that: a) there is no connection between the seriousness of roentgenologic deformations and equilibrium troubles; b) the damage of the periphery is not characteristic; c) the complaints and symptoms are explained by the hypoxia of vestibular kern-areas as well as by damages of receptors in cervical muscles, bands and joints; d) hypotension and other central vascular damages form an important factor in the development of equilibrium troubles.


[On the physiopathologic reactions of pharyngeal tonsil from the clinical standpoint (author's transl)]. On the basis of personal experiences the authors isolate two forms of pharyngeal tonsil hypertrophy: a physiological and a pathological one. The first one corresponds to the requirements of the organism which is not completely mature immunologically, it may be quite considerable but causes no disturbances in breathing through the nose or in the function of Eustachian tubes. The pathological hypertrophy of pharyngeal tonsil is due to a parenchymal inflammation caused by viruses with a typical pathogenesis. The authors describe six diagnostic criterias of the pathological hypertrophy of pharyngeal tonsils. Using these criter as they analysed 100 cases of adenotomy from the year 1969 and they have found that in only 38 cases the operation was done for pathological hypertrophy while in 62 cases hypertrophy was physiologic. Adentomy gives good results in cases of pathological hypertrophy but in cases of physiologic hypertrophy it may cause adverse results.


[The rate of growth and the production of bacterioplankton in the Volga]. The time of generation and production of bacteria were assayed in the Volga river. The time of generation of bacterioplankton was ca. 35.6 to 62.1 hrs per season during different years. The mean daily production of bacteria during a season was 30-50% of the biomass. The duration of vial exposition for estimating the time of generation and production was determined experimentally for conditions of the Volga.


A cytoplasmic gene for partial suppression of a nuclear pleiotropic respiratory deficient mutant in the petite negative yeast Schizosaccharomyces pombe. The nuclear pleiotropic respiratory-deficient mutant pet1 (previously M126) exhibits cytochromes aa3 and b deficiencies accompanied by loss of the oligomycin-sensitivity of the mitochondrial ATPase. The mutant pet1, unable to grow on glycerol, growth on glucose. The latter phenotypic trait symbolized by ANAS-D, exhibits a high frequency (2 to 4 X 10(5)) Of spontaneous suppression into Antimycin A-resistant strains. Mutagenesis with MnCl2 increases by a factor of 10(2) the frequency of ANAR-D derivatives. This suppression is partial since none of the suppressed strains is able to grow on glycerol even when respiratory functions and cytochromes activities are restored as in the pet1 [SUP2] strain. In the latter strain it is concluded that the extralocus suppressor gene [SUP2] is responsible for the ANAR-D trait. Tetrad analysis in a cross homozygous for pet1 demonstrates a non-Mendelian segregation pattern for the SUP2 suppressor gene. In stable diploids, homozygous for pet1, the [SUP2] suppressor exhibits a mitotic segregation pattern. Furthermore the transmission of the [SUP2] gene is decreased by ethidium bromide treatment. Therefore, the [SUP2] suppressor gene responsible for partial suppression of the nuclear pleiotropic phenotype in mutant pet1 is of cytoplasmic heredity.


[Zinc treatment of acrodermatitis enteropathica (author's transl)]. Treatment of acrodermatitis enteropathica with zinc sulfate, first described by Moynahan and Barnes in 1973, has been widely accepted. We have treated a case of acrodermatitis enteropathica successfully with this drug. The 14-year old boy had to discontinue clioquinol because of a partial opticus atrophy. The skin lesions deteriorated acutely. Following zinc sulfate treatment the lesions rapidly disappeared and the general health of the patient greatly improved. Small doses of zinc sulfate are sufficient for maintenance therapy. The pathogenesis of acrodermatitis enteropathica is reviewed and the modes of action of zinc therapy are considered.


[Origin and significance of perioral dermatitis (author's transl)]. We report on 888 patients with perioral dermatitis treated in our department from 1969-1975. The patients are evaluated according to age, sex and duration of treatment with fluorinated corticosteroids. The enormous increase of morbidity and the importance of highly effective topical corticosteroids are emphasized.


Mutagenicity of streptozotocin and several other nitrosourea compounds in Salmonella typhimurium. The following nitrosourea compounds were compared for their ability to induce mutation (to histidine independence) in the histidine-requiring auxotroph Salmonella typhimurium his G46: MNU, streptozotocin (SZ, streptozocin) and its analogs SZA1 and SZA2, and the antitumor drugs BCNU, CCNU and DCNU. At equitoxic doses SZ, SZA1, SZA2 and MNU were almost equally mutagenic causing 150, 42, 140 and 170 mutants/106 survivors at 20% lethal dose (ID20) ALTHOUGH, ON A WIEGHT BASIS, SZ was the most mutagenic of all the compounds tested. At ID20 BCNU, CCNU and DCNU gave about 0.5 mutants/106 survivors. Our results show that these nitrosoureas, in common with many other drugs (such as cyclophosphamide, daunomycin, etc.) used in cancer chemotherapy, are highly mutagenic. The implication of our results in the screening of drugs for their mutagenicity to man is discussed.


Association of Salmonella mutants with germ-free rats: characterization of the reverse mutational response to 2-nitrofluorene. Salmonella typhimurium strain TA1538 described by Ames, in association with otherwise germ-free rats, colonizes the gastrointestinal tract. The revertants enumerated in the feces of each of these rats varies in a coordinated manner in relation to the day on which the measurement is made. In response to the oral ingestion of a single dose of 2-nitrofluorene, the concentration of revertants in the feces increases and then returns essentially to control values within 6 days. When these rats are challenged repeatedly with a similar oral dose of 2-nitrofluorene the revertent concentration in the feces remains elevated for a progressively longer time. A change in phenotype of strain TA1538 during prolonged association rather than a change in the biology of the rat seems to explain this phenomenon. Firstly, germ-free rats exposed repeatedly to 2-nitrofluorene and then associated with strain TA1538 do not have the prolonged response characteristic of multiple challenges with 2-nitrofluorene. Secondly, strain TA1538 reisolated after several weeks of association with the otherwise germ-free rat shows other alterations such as decreased sensitivity to 2-nitrofluorene in the pour plate assay and a decreased sensitivity to crystal violet. In spite of limitations imposed by these alterations in strain TA1538, it is possible to demonstrate a dose-response relationship between the amount of 2-nitrofluorene ingested and the concentration of revertants in the feces of exposed rats.


The mutagenic activity of hydroxyurea in Chlamydomonas reinhardi. Hydroxyurea, an inhibitor of ribonucleotide reductase, increases the frequency of streptomycin resistant mutants in liquid cultures of Chlamydomonas reinhardi after 45 h incubation. After more prolonged incubation in hydroxyurea medium the frequency of streptomycin resistant mutants declines. This may be due to the slower growth rate of streptomycin resistant mutants compared to wild type cells in hydroxyurea containing medium. Studies on solid medium show that both the rate of forward mutation to streptomycin resistance and reverse mutation to nicotinamide independence are increased several fold by growth on hydroxyurea.


Mammalian host- and fluid-mediated mutagenicity assays of captan and streptozotocin in Salmonella typhimurium. The mutagenicity of captan and of streptozotocin was tested in vivo by reversion of hisG46 base-pair substitution histidine auxotrophs of Salmonella typhimurium in the peritoneal cavity or in blood, plasma or urine of rats or mice. Genetic response was determined by the frequency of revertants (quantitative test) or by the number of revertants per plate (semiquantitative test). In quantitative HMA captan gave negative results following 3 hourly 500 mg/kg s.c. doses or 1000 mg/kg oral dose in mice with the hisG46 mutant or 2000 mg/kg oral dose in rats with the hisG46, uvrB (TA1950) mutant. The positive control SZN induced many reversions at 0.5 mg/kg i.p. or 10 or 100 mg/kg oral doses. In semiquantitative in vivo blood or urine assays captan gave negative results after a 250 mg/kg oral dose with hisG46. SZN in the same experiment gave positive results in both semiquantitative and quantitative in vivo blood assays following 1000 mg/kg i.p. or 2000 mg/kg oral doses in the rat with TA1950. Rat blood mixed with captan for 45 min before adding TA1950 cells inactivated 1000 mug captan/ml but not 5000 mg/ml in the semiquantitative test. Corresponding figures in the quantitative test were 500 mu/ml and 1000 mug/ml. Rat plasma inactivated the mutagenicity of about 10 times less captan than rat blood. Human blood inactivated about as much captan as rat blood. The mutagenicity of captan was inactivated more efficiently than of SZN by blood. The results of the experiments suggested that captan's mutagenicity is probably inactivated by glutathione of the erythrocytes. Rat S-9 liver microsomal fraction also strongly decreased captan's mutagenicity in a semiquantitative test with the R factor, uvrB, hisG46 (TA100) mutant.


Mutation induction by the antischistosomal drug F30066 in various test systems. The genetic activity of furapromidium (F30066), an antischistosomal drug, was studied in Salmonella typhimurium, Saccharomyces cerevisiae, Neurospora crassa and cultured Chinese hamster cells. The results show that F30066 induces gene mutations in S. typhimurium, N. crassa and Chinese hamster cells. This compound also causes gene conversions in S. cerevisiae.