Broth-dilution method for determining the antibiotic susceptibility of anaerobic bacteria. A broth-dilution method for performing antimicrobial susceptibility tests on anaerobic bacteria has been proposed. The medium used in the test was Schaedler broth, with incubation in a glove box with an atmosphere of 5% CO(2), 10% H(2), and 85% N(2), or in the GasPak system. Minimal inhibitory concentrations for selected antibiotics were determined, under these conditions, by using a conventional twofold dilution scheme for the antibiotics and a "categorization three-tube method" in which two or three clinically significant concentrations of each antibiotic were used. Minimal inhibitory concentrations obtained by both methods were very similar. The categorization method could be used routinely to test the antimicrobial susceptibility of anaerobic bacteria.


Clinical pharmacology of sisomicin.

Clinical pharmacology of sisomicin. Studies were conducted in 30 patients with neoplastic diseases. Twelve patients received sisomicin intramuscularly at doses of 20 mg/m(2) and 40 mg/m(2). The mean peak serum concentration occurred at 1 h and was 2.5 mug/ml and 4.0 mug/ml, respectively. Ten patients received intravenous sisomicin at doses of 30 mg/m(2) during 30-min infusion. Mean peak serum level determined at 30 min was 5.1 mug/ml. The levels gradually decreased and at 6 h was 0.6 mug/ml. The serum half-life was 160 min. Serum levels determined in eight patients who received sisomicin by continuous infusion at doses of 30 mg/m(2) every 6 h were greater than 1.4 mug/ml during the 6-h period. The urinary excretion of sisomicin during the 6-h period after intramuscular administration of 20 mg/m(2) and 40 mg/m(2) was 49 and 61%, respectively. The pharmacology of sisomicin is similar to gentamicin.


Comparative susceptibility of anaerobic bacteria to minocycline, doxycycline, and tetracycline. The comparative susceptibility of 622 recent clinical isolates of anaerobic bacteria to minocycline, doxycycline, and tetracycline was determined by an agar-dilution technique. In addition to Bacteroides fragilis, a variety of other anaerobic bacteria was resistant to achievable blood concentrations of tetracycline (55% inhibited by 6.25 mug/ml) and doxycycline (58% inhibited by 2.5 mug/ml). In contrast, minocycline was significantly more active (P < 0.05) than both doxycycline and tetracycline, and 70% of strains were inhibited by achievable blood concentrations of this antibiotic (2.5 mug/ml). The enhanced activity of minocycline was particularly striking for Peptococcus asaccharolyticus, P. magnus, P. prevotii, Peptostreptococcus anaerobius, and Bacteroides melaninogenicus. Further evaluation of the clinical efficacy of minocycline against anaerobic infections is indicated.


Comparative in vitro antifungal activity of amphotericin B and amphotericin B methyl ester. The in vitro antifungal activity of amphotericin B methyl ester (AME), a water-soluble derivative of amphotericin B, was compared to that of the parent compound against a variety of pathogenic and potentially pathogenic fungi. AME has a significant antifungal activity, but the activity of AME was slightly lower than that of amphotericin B. Among the yeast-like organisms, only the yeast cells of Sporothrix schenckii were more resistant than others to both antibiotics, with a minimal fungicidal concentration of 5 to 10 mug/ml. The yeast cells of other fungi were killed at concentrations of 1 mug or less of either antibiotic per ml. The filamentous forms of S. schenckii and Oidiodendron kalrai were more resistant than the filamentous forms of other dimorphic fungi to both drugs. The minimal fungicidal concentration for S. schenckii was 10 mug/ml and for O. kalrai, 50 mug/ml. The dermatophytes, phycomycetes, and dematacious and other potentially pathogenic fungi were inhibited fairly well by both drugs, but up to 50 mug/ml was required for fungicidal action. The water solubility and wide spectrum of antifungal activity of AME warrant evaluation of its chemotherapeutic activity against experimental fungal infections.


Biological activity of staphylococcin 162: bacteriocin from Staphylococcus aureus. Staphylococcin 462 is a proteinaceous inhibitor produced by Staphylococcus aureus strain 462. In broth cultures, susceptible S. aureus strain 140 and 19 respond to treatment with the bacteriocin by stopping growth and cell division. Examination of macromolecular synthesis by measuring the incorporation of radioactive precursors revealed that S. aureus 140 stops synthesizing protein immediately. After exposure to staphylococcin 462, the synthesis of deoxyribonucleic acid and ribonucleic acid is quickly inhibited also, but not as completely. Treatment of S. aureus 140 with the inhibitor causes a rapid drop in cellular adenosine 5'-triphosphate level to about 60% of control levels. Of the 70 strains of gram-positive bacteria tested for susceptibility to staphylococcin 462, 24 (34%), distributed among 7 genera, were susceptible.


Mechanism of plasmic-mediated resistance to cadmium in Staphylococcus aureus. The mechanism of plasmid-mediated resistance to cadmium in Staphylococcus aureus was investigated. Protein synthesis in cell-free extracts from resistant or susceptible bacteria was equally susceptible to inhibition by Cd(2+), but spheroplasts from resistant bacteria retained their resistance. Resistant bacteria did not have a decreased affinity for cations in general, nor was active metabolism required for exclusion of Cd(2+). The kinetics of Cd(2+) uptake into susceptible and resistant bacteria suggested that the conformation of membrane proteins in resistant bacteria may be important in the exclusion of Cd(2+).


Isolation and characterization of a gamma-thiochromanone-4-thiosemicarbazone-resistant mutant of vaccinia virus. gamma-Thiochromanone-4-thiosemicarbazone (TCT) inhibits the growth of vaccinia virus in BSCl cells by interfering with viral maturation. A mutant of the virus (TCT(R)) which is resistant to this drug was isolated. This mutant also exhibits resistance to another thiosemicarbazone related compound, isatin beta-thiosemicarbazone (IBT). There is a good correlation between the cross-resistance of the two mutants IBT(R) and TCT(R) to TCT and IBT, respectively, and the similar antipoxvirus activity of these two thiosemicarbazone-related compounds.


Mode of action of two streptococcus faecium bacteriocins. The mechanism of action of enterocins E1A and E1B, bacteriocins produced by Streptococcus faecium E1, was studied. The enterocins killed susceptible cells rapidly, but cell lysis does not appear to be involved directly. Susceptible cells could be rescued from the lethal damage by trypsin treatment only within 2 to 3 min after addition of enterocin E1A. Enterocins E1A and E1B inhibited protein synthesis and drastically reduced biosynthesis of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) but did not cause degradation of DNA or RNA. Enterocin E1A strongly inhibited the accumulation of isoleucine and caused rapid exit of previously accumulated isoleucine.


Susceptibility of anaerobes to cefoxitin and other cephalosporins. The in vitro susceptibility of 155 strains of anaerobic bacteria to five cephalosporin antibiotics was tested. Cefoxitin was the most active against 33 isolates of Bacteroides fragilis; 82% of the strains were sensitive at 16 mug/ml. At 64 mug/ml cefazolin and cephaloridine were also generally effective. Cephalothin and cephalexin were relatively inactive versus B. fragilis. Cefoxitin, cephaloridine, cefazolin, and cephalothin showed comparable activity against 122 strains of anaerobes other than B. fragilis. More than 90% of the strains were sensitive to each of these antimicrobials at 16 mug/ml. Cephalexin was the least effective cephalosporin against all species tested.


Production and mode of action of lactocin 27: bacteriocin from a homofermentative Lactobacillus. Lactobacillus helveticus strain LP27 produced a bacteriocin, lactocin 27, in dialyzable and nondialyzable forms. No evidence was obtained to indicate that lactocin 27 was under the control of extrachromosomal plasmids. Lactocin 27 had a bacteriostatic effect on the indicator, Lactobacillus helveticus strain LS18. It inhibited primarily protein synthesis without affecting deoxyribonucleic acid and ribonucleic acid synthesis or adenosine 5'-triphosphate levels. Treatment of susceptible cells with the lactocin did not cause leakage of ultraviolet-absorbing material, but caused the efflux of potassium ions and the influx of sodium ions. It adsorbed non-specifically to various bacterial species irrespective of their susceptibility to lactocin 27. However, the presence of specific receptors has not been ruled out.


Parenteral clindamycin phosphate: pharmacology with normal and abnormal liver function and effect on nasal staphylococci. Parenteral clindamycin was evaluated in 41 patients with a variety of infections. The four major findings were as follows. (i) Five hours after the intravenous administration of 600 mg of clindamycin, the mean serum concentration in patients with "moderate to severe" hepatic dysfunction was 24.3 mug/ml, and in those with normal liver function it was 8.3 mug/ml (P < 0.02). This suggests that the dose of clindamycin might be modified in patients with liver disease. (ii) There was a positive association between the 5-h serum clindamycin level and the degree of elevation of the serum glutamic oxaloacetic transaminase. (iii) No significant side effects were observed. Of 24 patients with preexisting hepatic dysfunction, 5 showed deterioration and 5 showed improvement of liver function during therapy. (iv) Whereas all pre-treatment isolates of Staphylococcus epidermidis from the anterior nares were susceptible to clindamycin, 6 of 9 post-treatment isolates were resistant, most probably due to selection of resistant organisms.


Susceptibility of various serogroups of streptococci to clindamycin and lincomycin. The minimal inhibitory concentration of lincomycin and clindamycin for a large number of strains from multiple serogroups of streptococci was determined. The median minimal inhibitory concentration for streptococci from groups A, B, C, F, G, H, L, and M and nongroupable organisms ranged from 0.02 to 0.39 mug of lincomycin per ml and from </=0.01 to 0.09 mug of clindamycin per ml. Among the group D strains, Streptococcus faecium and Streptococcus faecalis were resistant to lincomycin and clindamycin, whereas Streptococcus bovis and four American strains of Streptococcus durans resembled nongroup D isolates in their susceptibility to these agents. Occasional strains of nongroup D streptococci were highly resistant to lincomycin and clindamycin.


Effect of diuretics on urinary excretion of cephalothin in humans. Diuretics and antibiotics are frequently used concomitantly. The possibility of drug interactions led us to study the effects of several diuretics on the renal elimination of cephalothin. Five healthy volunteers received a constant infusion of 500 mg of sodium cephalothin per h for 9 h on 4 consecutive days. Each day, after the third hour of infusion, the subjects were given one of the following in varying order: (i) furosemide (1 mg/kg, intravenous), (ii) mercaptomerin (250 mg, intramuscular), (iii) mannitol (25 g, intravenous), or (iv) no diuretic (control day). Fluid losses were replaced hourly. Serum and complete urine collections were obtained each hour and assayed for creatinine and cephalothin (bioassay). Clearances (milliliter per minute) and urinary excretions (milligram per hour) of cephalothin did not differ either when the diuretic day values were compared with control day, or when pre- and postdiuretic results on the same day were compared. Creatinine clearances were not affected by diuretics except for a transient rise after furosemide.


Activity of three aminoglycosides and two penicillins against four species of gram-negative bacilli. Three aminoglycoside antibiotics and two penicillins were compared for their in vitro activity against 60 isolates of Serratia, Pseudomonas, Proteus mirabilis, and indole-positive Proteus sp. Testing was done by the agar dilution method using Mueller-Hinton broth solidified with 1.5% agar. The activity of amikacin, aminodeoxybutirosin, and gentamicin against Proteus and Pseudomonas, as related to their peak blood levels, showed no significant differences. Amikacin was the most active against Serratia marcescens. Results using Mueller-Hinton media in broth dilution tests correlated with the agar dilution method except for Pseudomonas aeruginosa. The minimal inhibitory concentration for aminoglycosides in agar was considerably greater than the minimal inhibitory concentration in Mueller-Hinton broth, and the disparity was related to the higher divalent cation concentration of agar. BL-P1654 and carbenicillin were similar except that carbenicillin was much more active against indole-positive Proteus sp. Additionally, the ratio of bactericidal to bacteriostatic concentrations of BL-P1654 was considerably greater than for carbenicillin.


Activity of cefazolin against dense populations of enterobacteria. The in vitro activity of cefazolin was assessed by continuous turbidimetric monitoring of cultures of gram-negative bacilli and the results were compared with those previously obtained with other beta-lactam agents using the same strains and methods. Cefazolin was found to induce rapid lysis of ampicillin-susceptible and -resistant strains of Escherichia coli at a lower concentration than any other beta-lactam agent tested; its stability to beta-lactamase, as judged by regrowth studies, was generally considerably greater than that of other antibiotics of this group. Tested against 103 ampicillin-resistant enterobacteria, cefazolin was found to be more active than cephalothin against E. coli, but no systematic increase in susceptibility to cefazolin was seen with other species. A study of cefazolin in an in vitro model which simulates the hydrokinetic features of the urinary bladder showed it to be as active as ampicillin against ampicillin-susceptible E. coli and as active as cephalothin against ampicillin-resistant E. coli.


Effects of adenine arabinoside on cellular immune mechanisms in humans. In vitro lymphocyte blastogenic responses to the commonly employed mitogens, phytohemagglutinin, pokeweed, and concanavalin A, were evaluated when adenine arabinoside (ara-A) in a concentration of 3 mug/ml was added to the culture materials. Similarly, blastogenic and cytotoxic responses to cell cultures persistently infected with herpes simplex virus 1, herpes simplex virus 2, and varicella-zoster virus were determined in the presence of ara-A. No depression of these cellular immune responses by ara-A was demonstrated. This was in contrast to the effect of cytosine arabinoside, which at a concentration of 3 mug/ml severely inhibited these immune responses. Further studies examined lymphocyte blastogenic responses to the mitogens and blastogenic and cytotoxic responses specific for the herpes group virus infecting patients who were subsequently treated with ara-A; determinations were made before, during, and after treatment. In vitro responses during and after treatment with ara-A were unchanged or often enhanced as compared to pretreatment values. Therefore, the antiviral chemotherapeutic agent, ara-A, does not appear to depress the host's cellular immune responses, which are vital to successful elimination of invading herpes group viruses.


Sequence of biosynthesis of the components of the polyene macrolides candidin and candihexin: macrolide aglycones as intracellular components. A sequential formation of the single components of the polyene macrolide candidin complex (heptaene) has been found. In addition to the three components occurring in the candidin complex at the end of the fermentation, two other "early" all-trans heptaene components have been characterized. They exist only during the phase of active biosynthesis of candidin. Two of the components of the polyene macrolide candihexin complex (hexaene) that have been described as lacking amino sugar were the only intracellular (mycelium-associated) components observed under conditions in which no extracellular polyene remained attached to the producing cell. The results indicate that glycosylation of the macrolide ring takes place during the secretion process.


Disparity between inhibitory and killing effects of BL-P1654. The activity of BL-P1654, a semisynthetic penicillin, was studied in vitro against Enterobacteriaceae and compared with carbenicillin against Pseudomonas. There was a marked diminution in bactericidal activity of BL-P1654 when tested in broth medium.


Rifampin disks in mycobacterial susceptibility testing. A comparison of rifampin susceptibility test results on 407 strains of mycobacteria using conventional medium in parallel with disk medium showed good agreement. Techniques are described for utilization of drug-impregnated disks in the preparation of medium and for a quality control screening procedure for disks.


Effects of divalent cations on binding of aminoglycoside antibiotics to human serum proteins and to bacteria. Binding of gentamicin and related deoxystreptamine-containing aminoglycoside antibiotics to proteins in human serum can vary significantly with changes in experimental conditions. The concentrations of divalent cations are important variables, and binding increases progressively as the concentrations of calcium and magnesium decrease. Maximal binding of deoxystreptamine-containing aminoglycosides to human serum is approximately 70% in the absence of divalent cations. The binding of (3)H-labeled gentamicin to Pseudomonas aeruginosa increases and its bactericidal activity against P. aeruginosa is enhanced in the absence of divalent cations. In contrast, binding of (3)H-labeled gentamicin to Escherichia coli and bactericidal activity against E. coli do not vary significantly in the presence and in the absence of divalent cations. Interference with uptake of gentamicin provides a plausible explanation for the observation that the minimal inhibitory concentration of gentamicin for P. aeruginosa increases as the concentration of calcium or magnesium in bacteriological media increases. Although significant binding of deoxystreptamine-containing aminoglycosides to plasma proteins does not occur under normal physiological conditions in man, the possibility remains that variations in protein binding of these aminoglycosides might be significant under pathological conditions.


Verdamicin, a new broad spectrum aminoglycoside antibiotic. Verdamicin is a new aminoglycoside antibiotic isolated from fermentation broths of a species of the genus Micromonospora, M. grisea. It has been differentiated from other known related antibiotics by a variety of chemical and biological methods. Its in vitro and in vivo spectrum of activity appears to be similar to those of gentamicin and sisomicin.


Evaluation of a rapid Bauer-Kirby antibiotic susceptibility determination. To reduce the incubation time requirement in the Bauer-Kirby antibiotic susceptibility test, comparisons were made of the test results at 18 to 20 h (standard) and 7 to 8 h (rapid) utilizing 100 recent clinical isolates. The zone diameters for 664 disks were monitored by using the standard classification: resistant, intermediate, or susceptible. The susceptibility determination was unchanged in 558 out of 664 instances (84.0%). An analysis of the remaining 106 sets revealed that an initial interpretation of intermediate in zone size, subsequently determined resistant or susceptible, accounted for 49 of the observed differences. The reverse changes, initial resistant or susceptible subsequently classified as intermediate, accounted for 20 of the changes. In five instances the interpretation changed from susceptible to resistant; in two cases the interpretation changed from resistant to susceptible. The remaining 30 determinations were classified as indeterminant due to (i) insufficient growth at the early (7 to 8 h) determination, and to (ii) zones which were so large that they could not be measured accurately. The data indicate that zone sizes when measured to the nearest 0.1 mm can be interpreted with reasonable accuracy and the results can be available 10 to 14 h sooner.


Purification of two Clostridium bacteriocins by procedures appropriate to hydrophobic proteins. Two clostridocins distinguishable by their different modes of action on Clostridium pasteurianum have been isolated, namely, butyricin 7423 found in cultures of Clostridium butyricum NCIB 7423 and perfringocin 11105 produced by Clostridium perfringens type A, NCIB 11105. Both were trypsin-susceptible proteins which were soluble in concentrated aqueous ethanol and were able to bind large amounts of the nonionic detergent Triton X-100. In the presence of Triton X-100, butyricin 7423 behaved as a hydrophobic protein in being concentrated in the polyethylene glycol layer of a three-phase partition system of dextran-Ficoll-polyethylene glycol. Their capacity to bind Triton X-100 was exploited in a purification procedure applicable to both bacteriocins. After aqueous ethanol extraction of an ammonium sulfate-precipitated fraction (and, in the case of the perfringocin, a heat-treatment step), a bacteriocin-Triton X-100 adduct was purified by gel filtration through Sepharose 6B. The bacteriocin was then freed of Triton X-100 by chromatography on Sephadex LH-20. Samples of butyricin 7423 purified in this way from different sources contained variable amounts of carbohydrate. Yet sodium dodecyl sulfate-gel electrophoresis revealed the existence of a polypeptide component of 32,500 daltons (+/-10%), which displayed the biological activity of butyricin 7423 in the absence of any detectable associated carbohydrate (or lipid). Preparations of perfringocin 11105 contained no carbohydrate or lipid and migrated in sodium dodecyl sulfate-gel electrophoresis as a single protein component of 76,000 daltons (+/-10%). It was concluded that both bacteriocins behave as amphiphilic proteins, and some implications of this finding are considered.


Phosphonoacetic acid in the treatment of experimental herpes simplex keratitis. In a rabbit model of herpes simplex corneal ulceration, 5% phosphonoacetic acid solution or ophthalmic ointment suppressed clinical disease and virus replication. The effect of 5% phosphonoacetic acid ointment was equivalent to that of 0.5% idoxuridine ointment in the treatment of this established herpetic eye infection.


Effect of rifampin on nasal carriage of Staphylococcus aureus. Initial studies indicate that rifampin may be useful for the treatment of Staphylococcus aureus infections. Because bacterial resistance to rifampin may develop rapidly, its widespread use could result in the emergence of a resistant flora. This study evaluates the effectiveness of rifampin in reducing the nasal carriage of S. aureus and the rate at which resistant mutants emerge in a tuberculosis hospital where the drug was widely used. Anterior nares cultures were performed four times over a 13-month period. Carriage rates of S. aureus were 1.7% in 227 patients receiving rifampin, 7.8% in 190 patients receiving other antituberculous therapy, and 14.2% in 98 hospital employees (rifampin-treated versus other patients, P < 0.003; rifampin-treated versus employees, P < 0.001; employees versus other patients, P = 0.157). All four strains of S. aureus isolated from patients on rifampin therapy were rifampin resistant. All 16 strains isolated from patients not on rifampin and 15 of 16 strains isolated from hospital personnel were susceptible. One instance of apparent spread of a rifampin-resistant organism occurred in a hospital attendant who had never received rifampin.


BL-S 640, a cephalosporin with a broad spectrum of antibacterial activity: properties in vitro. BL-S 640 was evaluated in vitro by comparison with cephalothin, cephaloridine, cefazolin, and cephalexin. The new compound was more active than the control cephalosporins against most major gram-negative and some gram-positive species. Moreover, its antibacterial spectrum included strains of Enterobacter, Proteus morganii, P. rettgeri, and Providencia stuartii, species generally resistant to the other cephalosporins. BL-S 640 was an effective bactericidal agent for strains of various species of Enterobacteriaceae. In human plasma, the compound was 58% protein bound.


BL-S640, a cephalosporin with a broad spectrum of antibacterial activity: bioavailability and therapeutic properties in rodents. The bioavailability and therapeutic properties of BL-S 640 in rodents were compared with those of cephalothin, cephaloridine, and cefazolin after parenteral administration, and cephalexin after oral administration. When given intramuscularly in dosages of 5 to 40 mg/kg, peak concentrations of BL-S 640 in the blood of mice were proportional to dose, but when given orally, they were proportional only up to a dose of 25 mg/kg. After either route of administration, the concentration of BL-S 640 in the blood declined at a slower rate than that of the control compounds. Rats receiving BL-S 640 orally excreted an average of 39% of the drug in the urine. BL-S 640 was highly effective in the treatment of mice infected systemically with a variety of pathogenic bacteria, its therapeutic efficacy in comparison with that of other cephalosporins being frequently in excess of what would have been predicted on the basis of comparative activities in vitro.


Microdilution technique for antimicrobial susceptibility testing of anaerobic bacteria. A microdilution technique using commercially available media and materials was developed and used to determine the minimal inhibitory concentrations (MICs) of clindamycin, chloramphenicol, tetracycline, minocycline, ampicillin, carbenicillin, cephalothin, and gentamicin for 101 anaerobic isolates. Representative strains of Bacteroides, Clostridium, Fusobacterium, Peptococcus, and Peptostreptococcus were tested. The use of Schaedler broth at pH 7.2, an inoculum of 10(5) to 10(7) colony-forming units per ml, and incubation at 35 C in an anaerobic glove box with an atmosphere of 80% nitrogen, 10% hydrogen, and 10% carbon dioxide resulted in good growth and easily interpretable results. After 48 h of incubation, 97% of strains tested were inhibited by 3.1 mug or less of clindamycin per ml and 98% were inhibited by 12.5 mug or less of chloramphenicol per ml. Tetracycline and minocycline inhibited 81 and 88% of strains tested in concentrations of 1.6 mug or less per ml and 1.6 mug or less per ml, respectively. Ampicillin inhibited all strains other than B. fragilis in concentrations of 3.1 mug or less per ml. Excluding certain strains of Bacteroides and Clostridium, carbenicillin in concentrations of 12.5 mug or less per ml and cephalothin in concentrations of 6.2 mug or less per ml inhibited all strains tested. Gentamicin was inactive although some strains of anaerobic cocci and Bacteroides were inhibited by 3.1 mug or less per ml. After 18 to 24 h of incubation, eight of the 101 strains had not grown sufficiently for MICs to be determined; for the 93 strains which had grown sufficiently, 93% of 744 MICs were the same or one concentration lower than the 48-h MICs.


Binding of aminoglycoside antibiotics to filtration materials. An investigation to study adsorption of gentamicin and other related aminoglycoside antibiotics to cellulose, diatomaceous earth (Celite), and Seitz filter sheets was carried out. Experiments with five aminoglycosides indicated that 30 to 100% of these antibiotics was adsorbed to cellulose depending on the ratio of antibiotic to adsorbent, and the total quantity could not be removed by acidification. Similarly, a study with gentamicin found adsorption to diatomaceous earth to be in the range of 33 to 98%. Neomycin and gentamicin were also readily adsorbed to Seitz filter sheets. The data indicate that large losses may occur during filtration of these antibiotics under certain conditions, and care should be taken to properly evaluate results during studies with these compounds in the presence of adsorbent materials.


Antimicrobial agents from marine algae.

Antimicrobial agents from marine algae. The antimicrobial activity of five compounds extracted from marine algae was tested against Staphylococcus aureus, Salmonella choleraesuis, Mycobacterium smegmatis, Candida albicans, and Escherichia coli. Three of the compounds, cycloeudesmol, laurinterol, and debromolaurinterol, exhibited activity at concentrations approaching that of streptomycin. None of the compounds inhibited all of the organisms tested. There appeared to be selectivity for gram-positive microbes.


Bactericidal activity of combinations of gentamicin with penicillin or clindamycin against Streptococcus mutans. Data derived from testing the bactericidal activity of combinations of penicillin with gentamicin or streptomycin and of clindamycin with gentamicin on nine isolates of Streptococcus mutans were analyzed by preparing isobolograms to determine the presence of additive, synergistic, or antagonistic effects. Synergy with penicillin-aminoglycoside combinations was found in two strains; additive effects occurred in seven instances with penicillin-gentamicin combinations; and antagonism occurred in eight instances with clindamycin-gentamicin combinations.


Gentamicin and gentamicin C1 in the treatment of complicated urinary tract infections: comparative study of efficacy, tolerance, and pharmacokinetics. The clinical efficacy, patient tolerance, and pharmacokinetics of gentamicin and the single component gentamicin C(1) were studied after single and multiple doses in elderly male patients. Patient tolerance was extremely good at the dose levels used. There was some evidence of renal function impairment due to repeated intramuscular doses of gentamicin, but not gentamicin C(1). The antibiotics were equally effective against the organisms present in the urine of these patients. The pharmacokinetics of the two antibiotic forms were similar, although gentamicin C(1) appeared to have a larger distribution space.


Inhibitory effects of lipophilic acids and related compounds on bacteria and mammalian cells. The inhibitory effect of lipophilic acids, antimicrobial food additives, and analgesics-antipyretics was examined at concentrations from 0.1 to 100 mM in bacteria (Bacillus subtilis and Escherichia coli) and mammalian cells (HeLa, human fibroblasts, and mouse neuroblastoma cells). Most compounds inhibit the growth of HeLa cells about as efficiently as that of B. subtilis. However, butyrate and propionate, as well as acetaminophen, antipyrene, phenacetin, and salicylamide, inhibit HeLa at millimolar concentrations whereas, at least 10 times higher concentrations are needed to inhibit B. subtilis. The concentrations needed to inhibit growth by 50% decrease with increasing octanol-water partition coefficients of the compound. Growth of E. coli is inhibited similar to that of B. subtilis by all compounds except butylbenzoate, decanoate, and linoleate which cannot penetrate the lipopolysaccharide layer. All growth inhibitors inhibit amino acid uptake into bacteria and their vesicles, and oxygen consumption in bacteria. In HeLa cells or human fibroblasts, neither amino acid uptake nor adenine 5'-triphosphate synthesis are inhibited by fatty acids at concentrations that completely inhibit growth. Short chain fatty acids (propionate, butyrate, and pentanoate) induce in HeLa the formation of cell processes. In neuroblastoma cells, grown in the presence of 10% fetal calf serum, butyrate also induces such processes which slowly continue to grow in length for at least 7 days; these processes differ in speed of formation, width, and cycloheximide susceptibility from the thin processes produced by serum deprivation alone.


Enzymuria in gentamicin-induced kidney damage. To assess their potential value as early indicators of gentamicin-induced kidney damage, lysosomal hydrolases were measured in the 24-h urines of rats receiving 30 or 60 mg of gentamicin per kg per day for 15 days. Proteinuria, urine osmolality, blood urea nitrogen, and creatinine clearance were also measured. Kidney tissue was examined by both light and electron microscopy. Beta-galactosidase, beta-n-acetyl-hexosaminidase, and alpha-fucosidase were sensitive indicators and were significantly elevated above control values by day 3 at both doses (P < 0.01). Proteinuria, urine osmolality, and tests reflecting glomerular filtration rate were later indicators of nephron damage. Changes by light microscopy were detected on day 5. Necrosis was most prominent in the proximal convoluted tubules on day 10. Electron microscopy revealed numerous cytosomes with myeloid bodies within the proximal tubular epithelium on day 5. Lysosomal enzymuria appears to be an early manifestation of gentamicin nephrotoxicity and may possibly be related to the lysosomal abnormalities seen on electron microscopy.


In vitro activity of cinoxacin, an organic acid antibacterial. The activity of cinoxacin, a synthetic organic acid antimicrobial agent, was studied and found to have in vitro activity similar to that previously reported for nalidixic acid.


Improved acetylating radioenzymatic assay of amikacin, tobramycin, and sisomicin in serum. The acetylating radioenzymatic assay of aminoglycosides was modified by using [(3)H]acetyl coenzyme A as cosubstrate. This modification reduces the cost of the method by at least one-half without sacrificing rapidity or accuracy.


Susceptibility of clinical isolates of Enterobacteriaceae to BL-S640, a new oral cephalosporin. The in vitro activity of BL-S640, a 7-(2-aryl-2-aminoacetamido)-3-(heterocyclic-thiomethyl) cephalosporin, was evaluated against 338 clinical isolates of Enterobacteriaceae in comparison with ampicillin, cephalothin, cefazolin, and cephalexin. Against Escherichia coli, BL-S640 was as active as cefazolin and more active than ampicillin, cephalothin, and cephalexin. BL-S640 was as effective as the other cephalosporins tested and far more active than ampicillin against Klebsiella and was more active than cephalexin against Proteus mirabilis and the indole-positive Proteus. The majority of Enterobacter, Serratia, and Citrobacter were resistant to ampicillin and all the cephalosporins tested. With rare exceptions, the zone of inhibition by the BL-S640 30-mug disk was either larger or the same as the zone obtained by the cephalothin 30-mug disk in the Kirby-Bauer disk susceptibility test.


Renal metastases simulating Kaposi sarcoma. Radionuclide scanning, an aid in diagnosis and treatment planning. A case of renal cutaneous metastases simulated Kaposi sarcoma and the condition was misdiagnosed as Kaposi sarcoma. A new technique was employed using the isotope technetium 99m as the compound sodium pertechnetate Tc 99m for the diagnosis and evaluation of the extent of Kaposi sarcoma. The failure to demonstrate a positive isotope scan in our case was a clue to the incorrect diagnosis of Kaposi sarcoma.


Hypopharyngeal and laryngeal involvement with Darier disease. The presence of mucosal Darier disease (keratosis follicularis) was evaluated clinically and histologically in four consecutive patients with moderate to extensive cutaneous manifestations of this disease. Fiberoptic endoscopy demonstrated hypopharyngeal or laryngeal involvement or both in each patient. A dearth of corps ronds and grains in these anatomical regions was observed histologically. The routine evaluation of mucosal involvement in Darier disease should result in a higher incidence of hypopharyngeal and laryngeal lesions than is currently known. Furthermore, the recognition of hypopharyngeal and laryngeal involvement with Darier disease must be emphasized because of the clinical similarity to leukoplakia and squamous cell carcinoma.


Contact urticaria syndrome. Contact urticaria to diethyltoluamide (immediate-type hypersensitivity). Contact urticaria refers to a wheal-and-flare response occurring on the application of chemicals to intact skin. Standard closed patch tests read at 48 hours after application yield misleading information; observations should be made instead using open patch tests 15 to 30 minutes after application. There are three major subdivisions of the syndrome: nonimmunologic cause (such as application of histamine), immunologic cause (immediate hypersensitivity), and uncertain cause (such as application of ammonium persulfate). Our patient had contact urticaria due to the insect repellent, diethyltoluamide. The experimental data suggest that this case was due to an immunologic response (immediate hypersensitivity) and demarcates the specificity of response. The immunologically mediated cases cover a broad spectrum of manifestations from contact urticaria only to local urticaria plus asthma and, in extreme sensitivity, includes anaphylactoid responses.


Incontinentia pigmenti achromians.

Incontinentia pigmenti achromians. A patient with incontinentia pigmenti archromians, who was born to consanguineous parents, is described. This is the first reported case from Iran, to our knowledge. A number of features of this disease belong more properly to classical incontinentia pigmenti.


Desmoplastic malignant melanoma.

Desmoplastic malignant melanoma. A 68-year-old man sought dermatologic attention for a tumor of the arm. Biopsy specimen showed abnormal, essentially amelanotic, spindle-shaped cells in the cutis, greatly fibrotic stroma, and focal epidermal invasion. Desmoplastic malignant melanoma was diagnosed. The lesion was widely excised and axillary lymphadenectomy performed; one node showed metastasis. Nine months later, he died with widespread metastatic disease. To our knowledge, this is the first report of this entity since its delineation in 1971 and the only case in which diagnosis was established on initial biopsy and followed by definitive therapy. Desmoplastic melanoma has been confused with benign fibrosis, invasive fibromatosis, and fibrosarcoma, and is another example, with morpheaform basal cell carcinoma and sclerodermoid metastatic lesions from breast carcinoma, in which desmoplastic stroma may obscure the epithelial nature of cutaneous neoplasm.


Pedunculated malignant melanoma.

Pedunculated malignant melanoma. A woman had a primary pedunculated malignant melanoma. This is a rare form of presentation and may result in clinical confusion with seborrheic keratosis, fibroepithelial papilloma, or granuloma pyogenicum. The aggressive nature of the lesion was indicated by the presence of erosion and bleeding. Though the tumor cells were present only in the pedunculated mass, it had metastasized to regional lymph nodes at the time of surgery.


Radon seed implants. Residual radioactivity after 33 years. Radon seeds, formerly used for vascular and neoplastic tumors, acne, and other dermatological disorders, are rarely, if ever, used today. Because the half-life of radon is 3.83 days, these hollow gold seeds filled with radon gas are usually left in situ permanently. A case is reported of a woman who had seeds implanted 33 years ago for a vascular lesion. The seeds were removed and found to have minute amounts of residual radiation but not sufficient to cause radiation damage. Since seeds are foreign bodies, removal is recommended if they are easily accessible.


Sensory radicular neuropathy.

Sensory radicular neuropathy. A patient had sensory radicular neuropathy. The patient demonstrated features characteristic of this entity: (1) recurrent trophic ulcerations of the hands and feet, (2) onset in early adulthood, (3) distal, dissociated loss of pain and temperature sensation far out of proportion to the loss of other sensory perceptions, and (4) complete sparing of motor function.


Acral keratoderma.

Acral keratoderma. Three siblings displayed an unusual form of keratoderma characterized by diffuse and striate hyperkeratosis of the palms and soles, hyperkeratotic plaques over the dorsum of the hands and toes, and linear hyperkeratotic lesions over the Achilles tendon area, ankles, elbows, and knees. The predominant location of these lesions led to the term acral keratoderma for this disorder. Histologically, besides thickening of all epidermal layers with that of the stratum corneum being most notable, various dyskeratotic changes were evident in the epidermis. Pedigree analysis of the family suggested an autosomal recessive inheritance pattern. There were similarities and differences between the type of keratoderma displayed by these three patients and that of patients described previously with the disorder known as keratoma hereditarium mutilans.


Congenital unilateral benign papillomatosis of the mouth. A 29-year old man had an unusual unilateral lesion of the mucous membranes of the mouth, including the lips, buccal mucosa, hard and soft palate, and uvula. The lesion was a conglomerate of tiny papillomas and had been present since birth. At the age of 8 years, a mass extending from the uvula into the pharynx was surgically excised. The histopathological findings showed acanthosis, papillomatosis, and an inflammatory infiltrate. The findings represent a rare case and perhaps a unique one, to my knowledge.


Polyvinyl chloride pyrolysis products. A potential cause for respiratory impairment. A limited investigation of respiratory and other symptom prevalence, plus before and after shift ventilatory capacity was conducted among a group of 17 meat wrappers exposed to pyrolysis products of polyvinyl chloride and a group of 21 control subjects. Exposed meat wrappers showed a higher prevalence of cough, phlegm, hay fever, and asthma than did the control group. The exposed group also demonstrated relative decreases in forced expiratory volume, one second (FEV1.0) and forced expiratory flow 50% (FEF50) after one shift of work; whereas, the controls showed an opposite tendency. These findings suggest that meat wrappers exposed to pyrolysis products of polyvinyl chloride might be adversely affected. The results, while suggestive, are not totally conclusive owing to the fact that there was not ideal matching of the exposed and control groups in regard to age, height, race, sex, and smoking status.


Cement, asbestos, and cement-asbestos pneumoconioses. The incidence and characteristics of cement-asbestos pneumoconiosis were compared with those of asbestosis and cement pneumoconiosis in three homogeneous samples of cases. The clinical, functional, and radiological features of cement-asbestos pneumoconiosis are similar to those of classical asbestosis, but the observed changes are less common and occur after a longer exposure.


Dental lead, blood lead, and pica in urban children. Lead storage in teeth was evaluated by examining the lead concentration in deciduous teeth of 32 children whose habits of pica and state of lead exposure had been studied when they were between 1 and 3 years of age. Concentratios of lead in their teeth depended on the reported amount of paint or plaster intake and the duration of exposure. The mean dental concentration of lead in exposed children was significantly higher than the mean value in 36 controls, who presumably did not have undue exposure to lead. A difference in dental lead concentration related to living area was noted. The significant difference in lead content of teeth between the two groups, even though the concentrations of lead in blood at 8 years of age were similar, emphasizes the importance of dental lead measurments for retrospective studies of lead exposure.


Trace composition of human respiratory gas. A multistage cryogenic trapping system was used to sample and concentrate trace organic constituents in human respiratory gas. Chemical analysis was conducted by gas chromatography and mass spectrometry. Respiratory compound identification and production rate data are given for eight human test subjects. This study reports on the use of the sampling technique to diagnose metabolic diseases and for application in the study of industrial exposure.


Heinz bodies formed in erythrocytes by fatty acid ozonides and ozone. Ozonides of the methyl esters of oleic, linoleic, linolenic and arachidonic acids were found to produce Heinz body inclusions in human and mouse erythrocytes. No simple relationships between structure and activity were noted. Concomitant with Heinz body formation, methemoglobin and loss of cellular thiols were observed. Methyl ozonides readily oxidized glutathione and 1 mole of oxidized glutathione was formed per mole of methyl oleate ozonide. Methyl ozonides catalyzed the formation of disulfide-linked interchain polymers between hemoglobin and ovalbumin. Heinz bodies were not produced with ozone in the absence of unsaturated lipids. Heinz bodies were observed in the blood of mice exposed to ozone (0.85 ppm) for 48 hours. These observations suggest that fatty acid ozonides could serve as a toxic chemical species formed on ozone inhalation and could explain the divergent protective effects of lipid antioxidants and thiol generating systems in vivo.


Dose-dependence of methylmercury metabolism. A study of distribution: biotransformation and excretion in the squirrel monkey. The distribution and excretion of different body burdens of methylmercury (MeHg) have been investigated in the squirrel monkey. In monkeys given weekly 0.8 mg/kg doses, orally, of 203-MeHg, a linear correlation was observed between the concentrations of radioactive Hg in the blood and brain to as much as a blood concentration of 1 mug/gm. Above this level, the ratio of concentration in the brain and blood was increased. The total Hg concentration in bile collected from the bile duct was 10% to 30% of that in blood, while the concentration in bile from the gallbladder approached that in the blood. The total Hg concentration in feces was always more than ten times that in urine. Biotransformation of MeHg to inorganic mercury has been demonstrated; in the liver about 20% of the total mercury was inorganic, in the kidney 50%, and in the bile 30% to 85%. In the brain less than 5% of the total mercury was inorganic. After a single 0.8 mg/kg dose, orally, of 203-MeHg, the halftime for total Hg in blood was 49 plus or minus 2.8 days, and in the whole body 134 plus or minus 2.7 days. During the first four days after dosing, the decrease in blood concentration was more rapid than that occurring later, due to a redistribution within tissue compartments. A differential distribution of MeHg within the brain has been demonstrated in animals that showed clinical signs of intoxication.


Rheumatoid arthritis in an urban South African Negro population. (1) An epidemiological study of an urban South African Negro community has been carried out in Johannesburg. Altogether 964 respondents were examined and in each case radiographs of the hands and feet were obtained. Rheumatoid factor tests were carried out on 404 serum samples. (2) Rheumatoid arthritis (RA) was graded 'definite' or 'probable' on the basis of a modification of the Rome criteria (Kellgren, Jeffrey, and Ball, 1963a). (3) In marked contrast to the findings in rural Africans the prevalence of RA in this community was similar to that in Caucasian populations. Five respondents (all elderly women) had 'definite' RA, giving a prevalence of 1.4% of the females and 0.9% of the total population sample over 15 years old. The prevalence of 'definite' and 'probable' RA combined was 2.6% for males, 3.7% for females, and 3.3% for all individuals over 15 years old. Prevalence increased with age, reaching a maximum in the 65- to 74-year cohort. (4) The form and severity of the clinical and radiological features were unlike the mild manifestations seen in rural African peoples and closely resembled the usual clinical picture of rheumatoid disease. (5) The latex fixation test was positive in 12.1% of the sera tested, which is similar to the high titres found in other African populations. No obvious cause for this phenomenon was found. (6) Several reasons for the marked difference in prevalence of RA between this urban African population and a rural African population are considered. Marked intraracial differences such as this point to the importance of sociological and environmental factors in the pathogenesis of rheumatoid arthritis.


Rheumatoid arthritis in a rural South African Negro population. (1) An epidemiological study of a rural African community has been carried out in the Western Transvaal. Altogether 801 respondents over 15 years old were examined; radiographs of the hands and feet were obtained in all these individuals. Serological tests for rheumatoid factor were carried out on 516 blood samples. (2) The diagnosis of inflammatory polyarthritis was based on a modification of the Rome Criteria of 1961. Two categories were defined: 'definite' and 'probable' rheumatoid arthritis. (3) In this population inflammatory polyarthritis was much less common and much milder in its manifestations than in European and American peoples. The prevalence of 'definite' rheumatoid arthritis was 0.12% and of 'definite' and 'probable' rheumatoid arthritis combined, 0.87. Such changes as were encountered on clinical and radiological examination were invariably mild; no respondent in the entire survey had clinical features that would have been accepted in the ordinary way as those of rheumatoid arthritis. (4) The latex fixation test (LFT) was positive in 8.9% of the sera tested; the modified LFT aftaer inactivation of the serum at 56 degrees C was positive in 15.1% of cases. Similar findings in West African populations have been explained on the basis of alteration of the immune response by widespread parasitic infections. No obvious aetiological factor of this type was found in the present survey.


Chronic monarticular synovitis. Diagnostic and prognostic features. Data have been analysed from a retrospective review of 151 patients with monarthritis of more than 3 months' duration, usually involving the knee joint. The largest group, 49 patients (32%), had synovitis of unknown cause, 44 (29%) had synovitis probably associated with osteoarthrosis and 13 (9%) were diagnosable at presentation as having rheumatoid arthritis according to American Rheumatism Association (1959) criteria, which include serological and histological findings. There was only one case of tuberculous synovitis. Twelve of the thirteen patients diagnosed as rheumatoid arthritis developed involvement in other joints. In most other conditions, however, including synovitis of uknown cause, the prognosis was favourable, with either improvement or complete remission.


Survey of joint mobility and in vivo skin elasticity in London schoolchildren. A survey of joint mobility was conducted in 295 healthy children between the ages of 5 and 10 years who attended a London primary school. Estimates of the commonly used measurements, that is passive dorsiflexion of the wirsts and ankles, passive hypertension of the elbows and knee, were too insensitive to detect any age effect. However, a method of estimating extensibility of the 5th metacarpophalangeal joint in response to a standard load detected a highly significant inverse correlation between joint mobility and age in the samples significant inverse correlation between joint mobility and age in the samples tested ( r = -0.586; P less than 0.0001). There was no apparement sex difference. Skinfold thickness using the Harpenden caliper over the 3rd metacarpal bone and the in vivo skin elasticity measured using a suction cup device performed on a sample of 78 of the children revealed no influence of either age or sex on these parameters. This is in sharp contradistinction to the effect of both age and sex in these two parameters in adults...


Empyema in rheumatoid arthritis.

Empyema in rheumatoid arthritis. Case notes of the last 67 patients to present at the Brompton Hospital with nontuberculous empyemas, and without malignant disease, have been examined. Three cases of empyema in association with rheumatoid arthritis (RA) were found, and these cases are reported. Previous literature concerning this association is reviewed. It is concluded that two types of empyema may occur in patients with RA. Some develop in association with nodular pleuropulmonary disease and the formation of pyopneumothoraces; in other cases large, recurrent, primary empyemas build up in the presence of active rheumatoid disease alone. As with rheumatoid pleural effusions, middle-aged men seem to be particularly susceptible.


Urinary manometry in patients with spinal cord injury: neurourological considerations in the rehabilitation of acute and chronic neurogenic bladder. Recordings of pressure within the bladder, urethra, rectum, and external anal sphincter with image intensification and videotaping were carried out in spinal cord injury patients with complete and incomplete lesions, during spinal shock and in the chronic stage. The behavior of the external urethral sphincter and the somatic and visceral motor reflexes of the sacral segments were studied, during and after spinal shock. During spinal shock the majority of patients retained sacral somatomotor activity, in the absence of visceromotor activity, and resistance values at the external urethral sphincter remained high. Vascular oscillations were recorded in the membranous urethra. The highest resistance found in the membranous urethra was at the distal part of the external sphincter.


Voluntary skeletal muscles: a unifying theory on the relationship of their electrical and mechanical activities. Experiments designed to examine the relationship between electrical and mechanical events in voluntarily contracting human muscle were performed. Experiments reported in the literature, as well as our own, were categorized according to technique into one of four types: (1) isometric-isotonic, (2) isometric-anisotonic,(3) anisometric-isotonic or (4) anisometric-anisotonic. A general relationship between the absolute value of the surface electromyogram (the absolute value of E and the force (F) generated by the contraction is proposed. This is the integral of the absolute value of E dt = k-1integralF dx i-2integralF dt, where k-1 and k-2 are constants. In the isometric-isotonic condition, this equation reduces to a linear relation between the average electromyogram and the force of contraction. A quadratic relation exists in the isometric-anisotonic, constantly increasing contraction, between the integrated electromyogram and the force of contraction. Also, this equation predicts linear relations for anisometric-isotonic contractions, and quadratic relations for an accelerated rate of contraction, between the average electromyogram and force of contraction. Both the data reported in the literature and our data provide confirmatory evidence for the unifying theory offered in this paper.


Thermography: an aid in the management of insensitive feet and stumps. Infrared thermography contributes to the care of insensitive limbs. The inflammatory response of near damaged or damaged tissue presents areas of increased heat on the surface which can be detected and followed. Thermography was found to be a valuable aid to the established management methods used for insensitivity problems including management of healing and freshly healed ulcerations, management of neuropathic bone and joint problems and fitting of prosthetic devices and custom shoes. The most important contribution thermography offered was the detection of irritated tissue prior to frank breakdown often in time to prevent permanent injury if quick and effective management followed.


Paraspinal electromyographic abnormalities as a predictor of occult metastatic carcinoma. Profound membrane irritability localized primarily to the paraspinal muscles was the major electromyographic criterion proposed by LaBan and associates to predict the early presence and localization of spinal metastatic disease. A retrospective review was recently conducted to determine the accuracy of this interpretation and the effect of the electromyographic report on the attending physician's subsequent workup. In an analysis of 1800 electromyograms at Riverside Hospital, 91 cases were found which met the following criteria: (1) three or more paraspinal segments involved, (2) little or no membrane irritability in the anterior rami, and (3) no previous surgery on the paraspinal area. The proven discharge diagnoses were carcinoma in 24%, herniated nucleus pulposus in 28%, degenerative disc disease in 16%, diabetes mellitus in 9% and miscellaneous in 8%; in 15% no diagnosis could be made. We were unable to differentiate some cases of herniated nucleus pulposus from carcinoma using such criteria as profoundness of levels or number of spinal segments involved. There are partial explanations of why only paraspinal segments may be involved with profound changes in the diseases mentioned, but no explanation for the widespred involvement in localized disease such as a herniated disc. At our hospital it was interesting to note that internists infrequently order myelography or cerebrospinal fluid analysis while orthopedists, neurosurgeons and neurologists rarely order metastatic surveys.


Biofeedback treatment of foot-drop after stroke compared with standard rehabilitation technique: effects on voluntary control and strength. The effectiveness of biofeedback training was compared to conventional physical therapy training in 20 adult hemiparetic patients with chronic foot-drop. They were randomly placed into two groups of ten patients each: the first group treated over five weeks with therapeutic exercise and the second group treated over five weeks with therapeutic exercise plus biofeedback training. In the second group receiving the biofeedback training the increase in both strength and range of motion was approximately twice as great as in the first group. The improvement displayed by even the first group of patients suggests that a potential for functional improvement exists that is often unexploited. The addition of biofeedback facilitates the process. Four patients in the biofeedback group achieved and retained conscious control of dorsiflexion; three of them are now able to walk without the use of the short leg brace.


Optimal stimulus parameters for minimum pain in the chronic stimulation of innervated muscle. The degree of pain reported by ten volunteers upon electrical stimulation of their peroneal nerves was measured while stimulus parameters were varied. The responses were compared for stimulations, all of which produced the same amount of ankle torque. The stimulation parameters examined were pulse duration, 0.3 and 1.0 msec; repetition frequence, 20, 50 and 100 hertz; pulse shape, square wave and exponential wave; impedance of stimulator output, constant voltage and constant current; direct current bias, positive or negative to the stimulus; and wave phase, uniphasic and biphasic. Pulse duration of 0.3 msec and constant voltage output were the only two parameters significantly associated with minimum pain response. Analysis of voltage and current wave forms for the different stimulus parameters indicated that the sensation of pain was dependent upon the total amount of electrical charge delivered to the tissue with the pulse.


Physical training: comparative responses of middle-aged adults. The purpose of this investigation was to assess the adaptations of middle-aged women and men to a ten-week physical training program. Before and after training on a treadmill maximal oxygen uptake (VO2 max), heart rates and blood lactate were measured. Also, heart rates during submaximal exercise were observed. Additional measurements were made for body fat (skinfold method), resting blood pressure, heart rate and vital capacity. The training program consisted of a 30-minute walking and jogging exercise, three to four days per week. As a result of the training, oxygen consumption at exhaustion increased from 1.72 to 2.18 liters-min (29.2 to 37.4 ml/kg times min) for the women; 2.78 to 3.42 liters-min (33.7 to 41.8 ml/kg times min) for the men. The mean weight loss for the groups (0.7 kg and 0.8 kg) was negligible. Estimates of body fat (skinfold method) showed a significant loss of maximal exercise decreased significantly. No significant decreases in basal heart rate, blood pressure or vital capacity were observed. These data suggest that sedentary middle-aged women respond to vigorous physical training much like sedentary middle-aged men do.


Physical conditioning of less fit adults by use of leg weight loading. Physical conditioning using weighted ankle spats was evaluated in eight men in the age range 33 to 45 years (mean, 38.4). Evaluation consisted of pretraining and posttraining heart rate (HR) and oxygen uptake (VO2) responses to five submaximal work loads: cycling six minutes at 600 kilopond meter per minute (kpm/min); level walking for ten minutes at both 4.0 and 5.6 km/hr with and without a 1.5-kg weight spat added to each ankle. After the initial baseline evaluation, subjects wore 1.5-kg weight spats on both ankles for three weeks and were reevaluated; during the next three-week period weight was increased to 2.25 kg per ankle. Following the six-week evaluation period, subjects did not wear ankle spats, and detraining was evaluated after three weeks. A control group of four subjects was evaluated at these same submaximal work loads on three different occasions with three-week periods between evaluations. The experimental group wore the spats about 13.5 hours per day and averaged 6.85 km/day (4.25 miles per day) during training. After six weeks of training, submaximal HR decreased 6 to 9 beats per minute (P smaller than 0.05) from pretraining values for all five submaximal work loads; predicted VO2 max and predicted work capacity to achieve a HR of 170 beats per minute increased by approximately 10%. Detraining submaximal HR responses increased slightly, but not significantly, from post six-week training responses. Control group submaximal responses were unchanged between evaluations. It was concluded that individuals who initially possess a low level of cardiorespiratory fitness may have a low threshold for training. Thus, leg weight conditioning may be extremely useful for rehabilitation of patients and for sedentary middle-aged men as special adaptation prio to more high intensity training.


Leg-lift strength test with electrogoniometric analysis of knee angle. Twenty-four male volunteers took part in four different leg-lift strength tests to study the effects of (a) holding bar in hands, (b) lunging, (c) belt slippage and (d) changes in knee angle. Test method A involved the use of the traditional bar and belt with no restriction of lunging. Test method B was the same as test method A with the exception that lunging was controlled. Test method C involved the use of experimental bar and belt with lunging controlled. Subjects were not allowed to hold the bar in this test. Test method D was the same as test method C except that the subjects were instructed to grasp the bar with their hands. The results showed that most accurate strength scores were obtained with test method C in which experimental belt and bar were employed to eliminate the use of hands, minimize belt slippage and control lunging.


Sexuality and spinal cord injury: some psychosocial considerations. Sexual functioning in patients with spinal cord injury has been the subject of considerable research interest in recent years. There have been numerous studies of both physiological and psychological aspects of sexual functioning, but only the physiological part of this literature has been organized in a systematic fashion. This paper reviews 33 articles that deal mainly or exclusively with psychosocial aspects of sexuality. It is observed that the psychosocial literature in this area is relatively diffuse, dealing with concepts that are inadequately specified and validated.


Canine gallbladder bile. Effects of proximal gastric vagotomy, truncal vagotomy, and truncal vagotomy with pyloroplasty on volume and composition. Three groups of four dogs each underwent proximal gastric vagotomy, truncal vagotomy, or truncal vagotomy with pyloroplasty. Two dogs had sham operations. Gallbladder bile was aspirated and measured. Aliquots were cultured and assayed for cholesterol, phospholipid, and bile salts initially and at subsequent laparotomies. Both truncal vagotomy groups showed marked increases in aspirate volume at subsequent laparotomies. The sham and proximal gastric vagotomy groups showed a small initial decrease in mean aspirate volume without further significant changes. When the bile assay data were plotted on triangular coordinates, all point for all groups remained well within the area of cholesterol solubility. Nevertheless, two dogs in each truncal vagotomy group were found to have gallstones. No stones were found in the sham and proximal gastric vagotomy groups. Proximal gastric vagotomy appears to preserve fasting gallbladder bile volume and does not alter bile composition in the dog.


Intestinal blood flow. An evaluation by clearance of xenon Xe 133 from the canine jejunum. Clearance of a parenchymal injection of xenon Xe 133 from the jejunum was used to asses changes in tissue perfusion produced by variations in superiorr mesenteric artery flow resulting from partial aortic occlusion. Disappearance of xenon from submucosa and muscularis was similar and reproducible. The biexponential function of the isotope clearanc exhibited a rapid initial component representing mean flow. Calculated xenon clearance rates, expressed as half-times for isotope disappearance and plotted as a function of decreasing superior mesenteric artery flow, were characteristically rapid for a broad range of superio mesenteric artery flows (90 to 600 ml/min). With reduction of superior mesenteric artery flow beyond 80 plus or minus 10 ml/min, tissue clearance of xenon was markedly prolonged. Adequate perfusion of the vascular compartments of the small bowel as measured by xenon clearance was maintained until 80% reduction of superior mesenteric artery flow.


Arteriovenous fistaul from rupture of abdominal aortic aneurysm. Two patients with spontaneous aortocaval fistulas are described and compared with 67 cases reported in the English literature. Symptoms may vary widely; however, the presence of an expansile abdominal mass with a continuous bruit is usually diagnostic. The only successful management is promt repair of the vena caval defect and the aortic aneurysm. A third patient with spontaneous rupture of an abdominal aortic aneurysm into the left renal vein is alos described. Only five similar cases could be found in the work literature. Left flank pain, pulsatile abdominal mass, continuous bruit, and hematuria is the usual clinical picture. All of these cases involved an anomalous left retroaortic renal vein and all patients survived the necessary surgical correction. The operation of choice is closure of the defect in the retroaortic left renal vein and repair of the aneurysm.


Ophthalmic arterial blood pressures measured by ocular plethysmodynamography. The indirect measurement of ophthalmic arterial blood pressure is an important index in the understanding of cerebral vacsular hemodynamics. Ophthalmodynamometry (ODM), the prototype for such measurement, is, however, replete with difficulties that have limited its widespread use. A preliminary evaluation of a new technique for ODM identified as ocular plethysmodynamography, has yielded accurate opthalmic blood pressure data without the attendant problems. Reproducible values for bilateral ophthalmic arterial pressure levels have been determined in 30 normal volunteers and the levels correlated to brachial arterial pressure levels. In a series of patients with arteriographically demonstrable carotid obstructive lesions, the preoperative and postoperative ophthalmic arterial blood pressure relationships exhibited excellent correlation with the roentgenographic and intraoperative data.


Truncal vagotomy and pyloroplasty for duodenal ulcer. Two hundred sixty-five patients who underwent vagotomy and pyloroplasty for duodenal ulcer disease were observed postoperatively, 220 for two to ten years, with an average follow-up of five years. Vagotomy and pyloroplasty carried a higher overall recurrence rate (3.6%) than did subtotal gastrectomy and vagotomy (1%), largely because of the high ulcer recurrence rate more than two years after operation for massive bleeding (9.2%) rather than that following elective operation (1.8%). Thirty-five percent of these patients with recurrent ulcers did well with medical management and did not require a second operation. The mortality of vagotomy and pyloroplasty for a massively bleeding ulcer (11%) was less than that following subtotal gastrectomy (21%). The mortality of elective vagotomy and pyloroplasty was 1%.


Esophagogastric fistula. A complication of combined operations for esophageal disease. Esophagogastric fistula developed in two patients following operations combining fundoplication and other operative procedures on the esophagus. To our knowledge, this complication has not been previously reported or described. Accurate endoscopy and appropriate barium roentgenographic studies provided the definitive diagnosis. A second reconstruction was successful in one patient; conservative treatment was sufficient in the other.


Antiperistaltic ileal segment in the prevention of ileostomy diarrhea. Diarrhea, often profuse, accompanied by skin excoriation and nutritional and electrolyte depletion is a major complication of ileostomy. In an attempt to improve the course of these patients, an experimental study using dogs was undertaken to investigate an antiperistaltic ileal segment for the prevention of ileostomy diarrhea. Ileostomies were created in dogs. All the dogs with ileostomies died within nine days of weight loss and massive electrolyte and water depletion. A second group of animals underwent creation of an ileostomy simultaneously, with an antiperistaltic ileal segment placed 30.5 cm proximal to the ileostomy. These dogs maintained their weight and electrolyte and water balance. The stools in the group with the reversed ileal segment became semisolid to solid, compared to the watery diarrhea of dogs with ileostomies only.


Membranous glomerulonephritis. An initial symptom of gastric carcinoma? A 51-year-old man was hospitalized and operated on for gastric carcinoma with widespread metastases and died two months after the laparatomy and biopsy examination. Two years prior to the operation, he deveoped nephrotic syndrome. Anaplastic carcinoma, linitis plastica form, of the stomach was found in the tumor biopsy examination and at autopsy. Light and electron microscopical studies of the kidney biopsy specimen taken at laparatomy confirmed the presence of membranous glomerulopathy. An immunologic basis of the concomitant appearance of malignant neoplasms and nephrotic syndrome is possible, based on reported cases. There is also a possibility that renal damage occurs more commonly in malignant neoplasms, but is not recognized clinically.


Intraoperative arteriography during femoral-popliteal bypass. Minor technical errors may jeopardize the patency of femoral-popliteal bypass grafts. In an attempt to detect such errors, intraoperative arteriography has been routinely employed. It allows immediate recognition and correction of the most common abnormal findings: intraluminal debris, intimal dissection, distal thrombosis, arterial spasm, and kinking of the graft.


Operative arteriography. A new variation. A technique of intraoperative arteriography for evaluating the technical construction of femoral popliteal bypass involves dierect injection of contrast material into the vein graft after construction of the distal anastomosis. This allows full assessment of the anastomosis and of graft position prior to transection of the graft or proximal femoral arteriotomy.


Primary closure of radical mastectomy. A new method. A transverse incision is reported with an oblique counterincision performed in such a manner as to satisfy all Halstedian criteria for tissue removal and to allow as little as possible skin incision to approach the clavicular area. Closure is planned so that there is no tenting of skin or limitation of shoulder motion.


Structural polypeptides of antigenically distinct strains of influenza B virus. Analyses of the polypeptide composition of influenza B viruses by 13 per cent SDS-polyacrylamide gel electrophoresis are reported. The viruses contained polypeptides of eight species ranging in molecular weight from 27,000 to 78,000. Four of them were glocypeptides and were selectively removed from the surface of the virion by Bromelain treatment. One of the blycopeptides was identified as viral neuraminidase. Three antigenically distinct strains of influenza virus, B/Lee/40, B/Massachusetts/1/71 and B/Hong Kong/5/72, showed an essentially identical electrophoretic picture, although strain-to-strain difference was observed in the migration rate of HA1 and HA2 polypeptides.


Cell mediated immunity in experimental rubella infections. Antibody and cell-bound immune response were assessed in rabbits inoculated by the intravenous route with Cenedehill or with wild rubella virus. Our results suggest that wild or attenuated live rubella virus induce a transient unresponsiveness of the lymphocytes to PHA stimulation in vitro and suggest also that this immunosuppression was due to the persistence of rubella virus in the lymphocytes.


Neurotoxicity of topically applied hexachlorophene in the young rat. Young rats 6 to 22 days of age are extremely susceptible to the neurotoxic effects of hexachlorophene given as a daily bath of undiluted antiseptic detergent containing 3% hexachlorophene (pHiso-Hex). At this age, most rats are clinically and histologically damaged by as few as two daily baths. Younger rats are relatively resistant, probably because they have less myelin to be affected; older rats cannot be poisoned by this route, probably because the more mature liver excretes the drug more effectively. Age-dose-response curves in rats are similar to those in humans. This experimental model is potentially useful in defining other characteristics of this drug.


Neurotoxicity of hexachlorophene in humans. II. A clinicopathological study of 46 premature infants. To assess neurotoxic effects of hexachlorophene in the human population previously shown to be most at risk, a blind clinicopathological analysis was made of all premature infants under 1,400 gm birth weight who survived at least four days and were examined by autopsy over a 7.5-year period. Repeated whole-body bathing of premature newborn infants in 3% hexachlorophene-bearing soap (undiluted pHisoHex) shows a significant statistical association with a vacuolar encephalopathy of the brain stem reticular formation. The prevalence of the vacuolar encephalopathy in premature infants on whom we have adequate brain stem histological information appears to be related to the number of exposures to hexachlorophene, the concentration of hexachlorophene, the thoroughness of rinsing, and other factors (including exposure to ultraviolet light).


Neuropsychological effects of chronic asymptomatic increased lead absorption. A controlled study. Twenty-seven asymptomatic children with confirmed chronic increased lead absorption were compared with 27 matched control children for evidence of neuropsychological impairment. Evaluation of each child included a complete history, physical examination, quantitative neurological tests, and comprehensive psychological tests. There was significantly increased incidence of hyperactive behavior in the subjects with increased lead levels, but there was no significant difference in any of the quantitative test results. Uncontrolled variables, especially lead absorption in infancy and adverse environmental pressures other than lead, still leave questions about the relationship between chronic lead exposure and behavior of intelligence.


Cerebral vasospasm and ruptured intracranial aneurysm. The literature concerning cerebral vasospasm associated with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysm contains no definitive study of patients to determine whether there is (1) any clinical picture consistently present coincident with known cerebral vasospasm, (2) any relationship between mortality and known vasospasm, and (3) any relationship between serious brain damage (morbidity) and known vasospasm. To answer these important questions, experience with 198 consecutive acute SAH patients (every patient had a cerebral angiogram demonstrating one or more intracranial aneurysms) was studied. The experience with these 198 consecutive patients led to the conclusions that (1) there is no clinical picture consistently present coincident with known cerebral vasospasm; (2) cerebral vasospasm has no effect on the mortality from SAH due to ruptured aneurysm; and (3) there is no relationship between the frequency and severity of the complications from surgical or conservative treatment and the presence or absence of vasospasm.


Cerebral blood flow. A predictor of recovery from ischemia in the gerbil. Cerebral ischemia was induced in gerbils by bilateral carotid ligation for periods of 10 to 40 minutes. Cerebral blood flow (CBF) was measured by hydrogen clearance. Following ischemia, ultimate clinical and electroencephalogram recovery could be predicted in every case within the first five minutes by recovery could be predicted in every case within the first five minutes by recovery of CBF to at least 100% of the control level. In animals without EEC recovery, the postischemic CBF was always less than 80% of control and progressively declined to zero. Residual flow during ischemia appeared to minimize the likelihood of brain death. The determination of ultimate brain death appeared to coincide with a major circulatory abnormality that is probably microvascular.


Water in brain edema. Observations by the pulsed nuclear magnetic resonance technique. The state of water in three types of brain edema and in normal brain of the rat was studied by the pulsed nuclear magnetic resonance (NMR) technique. In cold-induced edema and in osmotic edema both in cortex and in white matter, the water protons have longer nuclear magnetic relaxation times than in normal brain. The observed changes correlate with the water content of the brain tissue. In triethyltin induced edema, no change was found for relaxation times in the cortex, whereas in the white matter, an additional fraction was observed with much longer relaxation times, attributable to fluid within the vesicles in the myelin sheaths. Since the NMR technique is non-destructive, it is potentially applicable in the living patient as a method for the detection of brain lesions that are accompanied with changes of brain water.


Failure to confirm a vascular cause of muscular dystrophy. The vascular hypothesis of the cause of muscular dystrophy suggests that ischemia is responsible for the muscle fiber necrosis. A xenon 133 clearance study of muscle blood flow in Duchenne and other muscular dystrophies showed no obvious difference between the response to exercise and arterial occlusion compared with control subjects. Radioautographic study of distribution of 4-125l-antipyrine in skeletal muscle of mice with muscular dystrophy showed no abnormal areas of ischemia. A statistical examination was also made of the grouping of damaged fibers, one of the observations on which the vascular hypothesis was based. Only 0.9% of fibers undergoing phagocytosis occurred in groups of four or more fibers in greater frequency than would have been expected by chance, and 70% of such fibers were isolated. These studies argue strongly against the vascular hypothesis of the cause of muscular dystrophy.


Chronic cerebellar stimulation in the monkey. Preliminary observations. In a single monkey, the surface of the cerebellum was stimulated electrically for 205 hours with electrodes and parameter values similar to those currently used in humans for treatment of epilepsy. Im pedance of stimulating and nonstimulating control electrodes remained unchanged throughout an observation period of six months. Potentials evoked by cerebellar stimulation could be recorded from the cranium, providing a noninvasive technique of determining the level of current delivered to cerebellum. Examination of the implantation site showed marked meningeal thickening surrounding the stimulating electrodes. Such thickening was not observed surrounding a control set. Light and electron microscopical examination revealed severe loss of Purkinje cells in tissue near the stimulating electrodes. There was also a moderate loss in other parts of cerebellar cortex down to a depth of about 1 mm from the exposed surface. Biochemical analysis revealed metabolic abnormalities consistent with the morphologic evidence of widespread tissue damage.


Lid-lag in the Guillain-Barré syndrome.

Lid-lag in the Guillain-Barré syndrome. Two patients with severe idiopathic polyneuritis demonstrated marked bilateral limitation of upper lid descent during the acute phase of their illness. Accompanying facial weakness does not adequately explain this phenomenon and the possibility of supranuclear levator dysfunction is raised.


Asymptomatic enlargement of the sella turcica. Forty-six patients with enlarged sella turcica and pneumographic evidence of an intrasellar mass were initially untreated. The courses were variable, and 50% did not require subsequent treatment. All patients with initial visual involvement developed progressive visual impairment. Of patients with clinical evidence of pituitary insufficiency, 66% developed visual field defects and required treatment. Only one patient, whose sole symptom was headache, was subsequently treated, and no asymptomatic patient developed subsequent symptoms and required treatment. Asymptomatic patients with an enlarged sella turcica should have an air study to exclude an "empty sella" syndrome or primary hypothyroidism.


[Subcutaneous rupture of the long extensor tendon to the thumb]. The "spontaneous" subcutaneous rupture of the tendon of the extensor pollicis longus is reported and the etiology and the pathologie are discussed. In our opinion is the transfer of the extensor indicis the only operation to do in this case and gives the best results.


[Revalgisation after intertrochanteric varus osteotomy in infancy]. The causes for revalgisation after varus osteotomies are examined in 153 follow ups. Varus osteotomies which slow an insuffizient fixation due to faulty technic or use of Kirschner wires demonstrate only a slight degree of revalgisation. In contrast, stable fixation leads to post-operative revalgisation directly proportional to the time of rigid fixation, we therefore recommend the removal of the fixation device after osseous consolidation, i.e. after 6 months.


[Microlesions of articular cartilage as a possible cause for post-traumatic osteoarthritis]. During operative treatment for intraarticular fractures osteochondral fragments were retrieved in 12 cases and sent for histological evaluation. The histology showed microlesions of the articular cartilage and subchondral bone. An etiological connection between these histological changes and posttraumatic osteoarthritis is being discussed.


[Stimulation of longitudinal growth of long bones through electrical current. Scintigraphic examinations on ribbit tibiae]. Report on szintigraphical examinations using 87-mSr in young rabbits treated by direct current of different intensity varying from 2.5 to 40 micro-Ampère. The current was applicated to one tibia using the other as comparison. Corresponding to the realised growth-increase by electric stimulation there was found an increased uptake of 87m-Sr in the electro-stimulated tibia in all 16 rabbits.


[Working time of bone cements].

[Working time of bone cements]. The period of applicability during polymerisation of four well introduced bone cements (Sulfix-6, CMW, Simplex, Palacos) was measured by a subjective method in function of room respectively conditioning temperature. Simultaneously temperature in the cement and mechanical admittance (transfer of oscillation of 750 Hz) were registered. The duration of working-up period and plymerisation period depends considerably from the room temperature. An increase of 10 degree C accelerates polymerisation by a factor of 1.5 to 2.0. The working time of the products differs widely. Increased room temperature means also increasing maximum polymerisation temperature. Mechanical admittance is an interesting measure for the objectivation of the working period. Discussing new ISO standards a proposal is made for more accurate determination of the end of the working-up period (set time).


[The results of Chiari's medial displacement osteotomy]. Results of follow-up investigations on 45 patients with hip operated between 1968 and 1973 after the method of Chiari are reported by the authors. The post-operative development of the C.E. angle (Wiberg) and of the acetabular inclination angle (v. Lanz) are discussed. Attention is drawn to the necessity of X-ray films taken in a second projection (Fauxprofil view). With the aid of arthrography of the hip joint it is demonstrated that the most important demands of acetabulum formation surgery, namely the antomical congruence of the joint components, can be achieved by means of pelvic osteotomy after the method of Chiari.


[The results of innominate osteotomy].

[The results of innominate osteotomy]. With the aid of radiological and clinical functional criteria, the results of 33 hip joints, operated after the method of Salter, are analysed. As in most cases a femoral detorsion occurs as a result of the pelvic osteotomy, basic coupling of the pelvic osteotomy with a femoral osteotomy dose not appear to be necessary. The importance of necessity of exact adherence to the principles of surgical technique, as described by Salter, as well as pre and post operative care, is stressed.


Experimental hyperthyroidism I. Hemodynamics and contractility in situ. The influence of experimental hyperthyroidism (intraperitoneal injection of crystalline L-thyroxine 1 mg/kg/day, 8-18 days) on cardiac mechanics in contractility in situ were studied in 30 hyperthyroid cats and compared with an euthyroid control group (n equals 30). 1. In hyperthyroidism left ventricular weight was considerably increased. Hypertrophy in hyperthyroidism represents a special case of myocardial hypertrophy, associated with an increase of myocardial performance. 2. Heart rate, systolic pressure, cardiac index, external cardiac work and tension time index were increased by 60-180 per cent. 3. Indices of contractility (dp/dtmax, t-dp/dtmax, dp/dtmax/IP) as well as isovolumetric force velocity relationships and VCE-max and Vmax demonstrated a considerable increase of contractility. Maximum rate isovolumetric pressure fall was increased by 120 per cent. Experimental hyperthyroidism is characterized by hypercirculation associated with increases of pressure, volume and velocity factors. The results are discussed with regards to the effects of increased cardiac mechanics on myocardial energy balance.


Experimental hyperthyroidism II. Mechanics of contraction and relaxation of isolated ventricular myocardium. The effect of experimental hyperthyroidism on myocardial mechanics was examined on isolated ventricular myocardium (right ventricular papillary muscle) of cats. 1. Isotonic muscle contraction and isometric tension development were largely unchanged compared with euthyroidism. 2. Isotonic contraction velocity and maximal isometric tension rise velocity showed considerable rises of between 41 and 78%. 3. Force-velocity relations of contraction showed changes with increases of contraction velocity with every degree of load. 4. Force-velocity relations of isotonic relaxation showed increases of isotonic relaxation maxima with comparable loads without any alteration of the typical course of the relaxation curves compared with euthyroidism. 5. Lowering the temperature (from 34 to 24 degrees C) produced a considerable fall of the raised contraction and relaxation velocity in hyperthyroidism whereas the values of muscle contraction and tension development important for the pump function were largely unchanged. It is concluded that the myocardium in experimental hyperthyroidism is characterised by a primarily velocity-related increase of inotropy. Lowering the temperature produces an effective fall of the raised velocity values. The mechanisms of the increase of inotropy and significance of the findings are discussed.


Biochemical genetics of alpha-amylase isozymes of the chicken pancreas. In the chicken population at large, three electrophoretically distinct pancreatic alpha-amylase isozymes were discovered. The isozymes were designated Pa 1, Pa 2, and Pa 3. The local population of chickens, however, possessed only isozymes Pa 2 and Pa 3 present as three phenotypes: Amy-2 B, consisting of isozyme Pa2; Amy2 BC, consisting of isozymes Pa 2 plus Pa 3; and Amy2 C, consisting of isozyme Pa 3. Pancreatic biopsy permitted the establishment of a breeding flock with defined amylase phenotypes. Matings of this flock established that amylases are inherited as codominant alleles at a single genetic locus. Further, there was no evidence of ontogenetic modification of the amylase isozymes. It was observed that amylase isozymes Pa 2 and Pa 3 each generated a family of at least three faster-migrating amylolytic proteins. These post-translationally modified amylases were designated Pa Xa, Pa Xb, and Pa Xc, where X represents the number of the progenitor amylase. Structural analyses of purified amylases demonstrated that all amylase isozymes are nonglycosidated, monomeric molecules of molecular weight 55,000. In addition, the data are consistent with the hypothesis that the faster-migrating amylases are produced by deamidation of asparagine and/or glutamine residues.


Local dilatory reserve in chronic experimental coronary occlusion without infarction. Quantitation of collateral development. The local dilatory reserve of the canine coronary vasculature was studied with the particle distribution technique. Normal ventricles and hearts with slowly progressive narrowing of both the left circumflex coronary artery and the right coronary artery were studied. In spite of chronic occlusion of 2 coronary arteries myocardial infarction did not occur in the majority of animals because of collateral development. Coronary reserve was determined by producing graded to maximal coronary vasodilation. In normal hearts flow increased homogeneously over the entire left ventricle. In hearts with chronic coronary occlusion coronary vasodilation produced non-homogeneous increases in flow: collateral dependent myocardium received less blood flow than myocardium supplied by normal coronary arteries. Early after coronary occlusion the total coronary reserve was less than normal and the dilatory reserve of collateral dependent vessels was markedly diminished. Late (6 months) after coronary occlusion the total coronary reserve was still below normal but the dilatory reserve of collateral dependent vessels had improved. A new quantitative index of collateral function is defined as the level of coronary flow (delivered through normal coronary arteries) at which collateral flow deviates from homogeneous perfusion. Collateral function, when so defined, increases by a factor of almost 6 times between 4 weeks (early after coronary occlusion) and 6 months (late after occlusion) after the implantation of occluding devices.


Serum esterase genetics in rabbits. III. A third allele on the Est-2 locus. A fast-migrating F' zone of the prealbumin serum esterase system of rabbits is demonstrated in low frequency in the breed Vienna White (stock Cpb:VW). Evidence is given that this zone is controlled by a third allele of the Est-2 locus. The zymotypic expression of this allele (Est-2-F') shows codominance in combination with the Est-2-F allele and complete dominance in combination with the Est-2-F' allele. In contradistinction to the F zones of the Est-2-F allele, the F' zone possesses no atropinesterase activity.


Gene action in fish of tetraploid origin. I. Cellular and biochemical parameters in cyprinid fish. In phylogenetically diploid and tetraploid Cyprinid fish species, erythrocyte volumes, protein contents, and mean activities of the enzymes LDH, 6PGD, and PGI per cell per active gene locus decline with increasing DNA contents. These findings are assumed to reflect an evolutionary tendency of polyploids to regulate their genic activity down to the level of the diploids.


Metabolism and fine structure of the Mg++-procaine-arrested perfused heart. Arrested rabbit hearts were perfused in normothermia for up to two hours by a cardioplegic erythrocyte-containing solution having an increased Mg++-, procaine-, and a reduced NaCl-content. After this time, hearts did not reveal any sign of anoxic or toxic damage in their metabolic pattern, in their ultrastructural picture, and in their functional capacity after reanimation. Despite a small loss in adenine nucleotide content, the ATP/ADP ratio and the PC content were raised. The contents of glycogen and glycolytic intermediates were normal or slightly reduced. After two hours of perfusion mitochondria showed no swelling, their membrane structure was unaltered. The myofibrils were well aggregated. The number of glycogen granules was increased. Hearts were reanimated after two hours of cardioplegia and could be loaded by pressure and volume.


Ontogeny of lactate dehydrogenase isozymes in chicken-quail hybrid embryos. The ontogeny of lactate dehydrogenase (LDH) isozymes was examined in avian hybrids and compared with the isozyme patterns of the parental species. Hybrids were obtained by crossing female Japanese quali (Coturnix coturnix japonica) with male domestic chickens (Gallus gallus domesticus). By use of starch gel electrophoresis and an enzyme-specific stain, traces of embryonic paternally derived LDH were detected in unincubated hybrid eggs. It was concluded that the embryonic genes coding for the B subunits of LDH are activated during the hours between fertilization and oviposition. In early blastoderms, a great excess of maternally stored LDH is present. In the hybrid, the predominantly maternal pattern of isozymes shifts during embryogenesis to a predominantly paternal pattern. This was considered evidence for differential allelic regulation of LDH inactivation. A progressive trend toward the establishment of the adult distribution of isozymes in various tissues was also observed in the hybrid and quail, and found to be similar to chicken LDH isozyme ontogeny.


[The effect of intravenous infusion of glucagon on the contractility of the left ventricular myocardum in man (author's transl)]. In the cases of 10 cardially healthy humans and 5 patients with heart disease, the left ventricular pressure as well as different parameters of contractility - deduced from the pressure curve and its first derivative - were determined by a catheter-tip manometer (Statham SF - 1). In particular the following values were concerned: dP/dtmax,-dP/dtmaxDP, the maximal calculated shortening velocity of the contractile elements according to the 2-component heart muscle model (VCEmaxTP) as well as with the Maxwell model (VCEmaxDP) and finally the (extrapolated) maximum shortening velocity (Vmax) under a fictive zero load. The examinations were carried out before and during a 10-minute infusion of 60 mg/kg glucagon and 10 minutes after completing the infusion. Besides glucagon also digoxin, etilefrin-HCl-1) and orciprenaline-2) were delivered and the same measurements were performed as with glucagon. A definite statement about the priority of any one of the named indices of contractility is rendered more difficult, because the enddiastolic pressure does not change substantially with glucagon. An unequivocal demarcation of frequency and pressure effects and of inotropic mechanisms as just as impossible, because, with the exception of VmaxDP, all parameters react quantitatively and qualitatively in an equal manner. On the basis of VmaxTP the result of glucagon is only a slight increase in the myocardial contractile capability, which would hardley suffice for the treatment of patients, who do not respond to digitalis. The decline of VmaxDP under glucagon cannot be explained. Under digitalis, etilefrin and orciprenaline, a similar dissociation of values for the maximum shortening velocity according to the 2- or 3-component-model of the heart muscle cannot be demonstrated.


Reduction of the size of acute, experimental myocardial infarction by Verapamil. The effect of 0.1 mg/kg Verapamil on the extent of the ischemic area following ligation of a branch of the left descending coronary artery was studied in anesthetized open chest dogs. The sum of the ST-segment elevation during the entire period of occlusion in the epicardial ECG was 15 mV in control infarction compared to 9 mV (p smaller than 0.0005) when Verapamil was infused after ligation. Mean flow in the left descending coronary artery was reduced by coronary ligation alone on the average by 23%, but augmented by Verapamil for 5% above pre-occlusion control flow. Corresponding to the rise in the coronary flow and the drop in perfusion pressure under the influence of Verapamil, the increase of left coronary artery resistance induced by coronary occlusion was diminished. The positive effect of Verapamil on the size of myocardial infarction as estimated from the epicardial ST-segment changes is probably not induced by coronary vasodilatation, but by the Ca-antagonizing effect of this drug, as described by other authors.